ERC Grants

Objective of the project:

A central question of economics is how scarce resources should be allocated among competing needs. Over the past two decades, economists and policy makers have come to increasingly appreciate the importance of market frictions – e.g., informational, or financial, – in hindering the efficiency of resource allocation. This in turn has led to an avalanche of carefully designed corrective policies: from those that address financial sector stability to those that aim to boost market competition. For example, the central bank interventions in secondary markets for asset-backed securities – markets plagued by information asymmetries during the great financial crisis of 2008-09, – proved crucial in limiting the damage to the global economy. The lessons learned were responsible for the swift monetary-financial and fiscal responses during the COVID-pandemic. However, an important dimension of the problem has been overlooked so far: what investments/technologies can and should firms themselves make/adopt to overcome the inefficiencies caused by market frictions?

The goal of this proposal is to advance the state-of-the-art by addressing this question from multiple angles, using novel conceptual frameworks, firm-level data, and quantitative models. The proposal comprises two parts, each focusing on inefficiencies stemming from a specific friction. Part I centers on financial frictions, exploring how firms choose investment technologies, such as asset specificity, considering their impact on borrowing capacity and the efficiency of asset allocation. Part II delves into information frictions, investigating how firms choose information acquisition strategies, such as data investments, anticipating the impact of imperfect information on the efficiency of resource allocation.

Vladimir Asriyan – Centre de Recerca en Economia Internacional (CREI)
CoG2025 – SH1 – Social Sciences & Humanitites – Individuals, Markets and Organizations

Nature and consumer culture in early modern Japan

The ‘consuming nature’ concept argues that non-elites developed a new way of engaging with nature during Japan’s Tokugawa period (1600-1868), amidst the changes brought about by early modernity. The ERC-funded J-NAT project will analyse the commercialisation of nature in early modern Japan, focusing on urbanisation, literacy and consumer culture. It will explore how nature as a leisure product varied by location, social status and sex and examine changes over time. Moreover, it will analyse 17th- to 19th-century objects and texts to show how commoners began to view plants and animals as commercial products and leisure activities, reshaping our understanding of early modernity in Japan. Project findings will be situated within early global modernities and will challenge the perceived divide between the Tokugawa and Meiji periods regarding the commodification of nature.

Objective of the project:

The central hypothesis of Consuming Nature is that a new mode of interacting with the natural world developed among non-elites during the social and economic upheavals of Japan’s Tokugawa period (1600–1868), with consequences for our understanding of “early modernity” in the Japanese case and beyond. Previous studies, both of Japan and of other regions, have examined early modern nature from the perspective of environmental degradation and resource management or elite philosophy and natural science. In contrast, the focus of this cultural historical study will be on a largely untapped corpus of objects and texts from 17th to 19th century Japan attesting to a new kind of (purchasing) power over nature, one which saw the commercialized enjoyment of plants, animals, and natural phenomena as consumer products and leisure activities among commoners.

The project will collate this corpus and analyse it in light of the characteristics associated with Japanese early modernity: rapid urbanization, increasing literacy, a commercial print industry, and a consumer culture concentrated in large urban centres connected to rural areas by improved communication and transport networks. How was the commercialization of nature as a leisure product linked to these so-called “early modern” developments? Did it also draw upon older traditions and institutions? How did this consumption of nature vary by urban versus rural locations, by social status or sex? Did it vary over time or by type of product?

The final stage will connect the project’s findings to the history of global early modernity/ies, and to research on nature and Japanese modernity, which usually takes the Meiji Period (1868–1912) as its starting point. It will interrogate the supposed rupture between the early modern Tokugawa period and the modern Meiji period when it comes to the consumption and commodification of nature, and will provide a scholarly framework for challenging Eurocentric teleologies of nature and modernity.

Rebekah Clements – Universitat Autònoma de Barcelona (UAB)
CoG2025 – SH6 – Social Sciences & Humanitites – Cultures & Cultural Production

Assessing the uncertainty of predictions of modern large-scale machine learning systems is crucial for understanding their limitations and the quality of solutions they provide, especially so when these systems are used for making decisions in the real world. Motivated by this need, this project addresses a variety of questions of uncertainty quantification and develops new methods for deriving statistical guarantees on the accuracy of outputs of ML systems.

Our methodology is inspired by an emerging line of work we call algorithmic statistics, which uses tools from the theory of algorithms to prove complex statistical statements. We propose to extend these techniques to the more challenging domain of analyzing modern large-scale machine learning systems, and develop a theory of Algorithmic Uncertainty Quantification. Using the newly developed tools, we will address diverse statistical tasks such as bounding the generalization error of machine learning algorithms, estimating the parameters of large nonlinear statistical models, or designing provably efficient algorithms for interactive decision-making problems.

The results will significantly advance the state of the art in well-studied areas of research such as statistical learning theory and reinforcement learning, not only by providing new tools for the analysis of existing algorithms and architectures but also by inspiring new principles for the development of the next generation of ML systems.

Gergely Neu – Universitat Pompeu Fabra (UPF)
CoG2025 – PE6 – Physical sciences & engineering – Computer Science & Informatics

A closer look at the Catholic Church’s environmental history

Fifty years ago, historian Lynn White Jr. criticised the Judeo-Christian tradition for exploiting nature. Recently, Pope Francis released an environmental manifesto, advocating against climate change. Has the Catholic Church embraced environmentalism? What challenges has it faced? The ERC-funded CATCH project will document the environmental history of the Catholic Church from the 1960s to the 2000s, highlighting its global influence on environmental issues. The project will explore how the Church has shaped environmental visions and politics. It will explore the Church’s role in environmental governance at international conferences and UN debates, as well as regional case studies in the Americas, Europe, Asia, and Africa. It will produce multiple academic publications and a documentary.

Objective of the project:

Fifty-six years ago, historian Lynn White Jr. published his “J’accuse” against the Judeo-Christian tradition, blaming it for fostering a culture that exploited nature. Half a century later, Pope Francis published an environmental manifesto, positioning himself as a champion against climate change. Has the Catholic Church (CC) embraced environmentalism? What have been its key environmental interventions, turning points, and internal and external frictions?
CATCH will provide the first comprehensive environmental history of the CC from the 1960s—when Vatican II intertwined with the hopes of the 1960s—to the 2000s, with the election of Bergoglio. Scholars have explored the intersection of religion and the environment from theological and philosophical perspectives, leaving historical relationships unexamined. This oversight is significant given the CC’s global influence, including its participation in major environmental conferences and its potential impact on 1.5 billion people. In what ways has the CC shaped environmental visions, politics, and realities?
CATCH aims to address this gap by researching the Church’s environmental engagement across multiple scales. Globally, it will examine its role in environmental governance at international conferences and UN debates. Regionally, it will analyze the CC’s diverse experiences of engagement with environmental issues through case studies in South and North America, Europe, Asia, and Africa.
The PI, with a strong background in environmental history and political ecology, will lead this groundbreaking research. The team will include 5 PhD students, 1 postdoc, and 1 research assistant, supported by 4 senior researchers—each an expert in one of the case studies—and an ethical advisory board with two leading theologians. The project will produce 5 PhD dissertations, a monograph, an edited volume, a special issue, 13 peer-reviewed articles, an open-access oral history repository, and a documentary.

Marco Armiero – Universitat Autònoma de Barcelona (UAB)
AdG2024 – SH6 – Social sciences & humanities – The Study of the Human Past

When market power tilts the balance and shapes inequality

In advanced economies, a handful of firms have captured an ever-growing share of profits, while workers’ share of income declines. This is what economists call ‘market power’. It is the ability of large firms to set prices, wages, and the rules of the game. The ERC-funded MACRO_POWR_DISTRBUTN project aims to explain how this power shapes inequality. Using data from Belgium and the USA, the project will study firm size, financial constraints, and automation to determine how these factors influence wages, profits, and investment. The project’s goal is to explain why some companies enjoy higher profits but pay proportionally less to labour and how smarter policies could restore balance between efficiency and fairness.

Objective of the project:

Market power is about the distribution of economic surplus between firms, customers and workers. In this proposal, I use modern heterogeneous agents macro tools that incorporate heterogeneity in firm productivity, in preferences, and in market structure. I investigate the macroeconomic mechanisms that link market power and distributional characteristics and formulate welfare-improving policies that lead to efficiency gains and re-distribution.

I propose a unifying framework of market power and distribution in general equilibrium, and use unique data to address the following 3 questions:

1. How does firm size determine monopsony power? Large firms have lower markups yet higher markdowns. This is a key determinant behind the lower labor share in superstar firms, but we have no mechanism that explains why. I propose to use the unifying framework and Belgian VAT transaction data combined with matched employer-employee data to quantify the economic mechanism by which markdowns vary in the firm size distribution.

2. How do financial frictions influence market power? Low productivity firms tend to face tighter financial constraints, leading to higher dispersion in the distribution of capital and technology. This in turn increases market power. I have access to data from a private bank (Caixabank) on a representative sample of firms’ payroll, accounts, as well as credit. Within the unifying framework I aim to quantify the impact of financial frictions on the distribution of market power.

3. How does labor-saving technological change affect the distribution of the labor share and market power? Technology adoption is driven by the firm’s attempt to increase profitability. Incorporating general equilibrium effects and market power, I propose to analyze the substitution patterns within and between firms with the introduction of new technologies. I will use US Census data to quantify the distributional effects of labor-saving technological change.

Jan Eeckhout – Universitat Pompeu Fabra (UPF)
AdG2024 – SH1 – Social sciences & humanities – Individuals, Markets & Organisations

A grammar of collocations

The language of native speakers is highly idiosyncratic. Especially collocations (natural word pairings such as ‘make a decision’ or ‘strong tea’) dominate our speech. In lexicology, collocations are typically seen as prefabricated units that must be memorised by language learners. Yet small-scale studies have shown that their being prefabricated does not mean that their construction is ad hoc. The ERC-funded MaPPLexiC project employs deep neural models for collocation recognition and classification as cognitive models, analysing their internal patterns to uncover a ‘grammar of collocations’. With a multilingual scope spanning Germanic, Romance, Finno-Ugric and Slavic languages, MaPPLexiC seeks to identify both universal and language-specific rules. Its findings will advance linguistic theory, enhance learning and translation tools, and help support under-resourced languages.

Objective of the project:

MaPPLexiC aims to fill the gap in modern language theories concerning the interpretation and description of one type of idiosyncratic word constructions that stands out in terms of its frequency of use and as a measure of language proficiency, namely lexical collocations, and refute the wide-spread assumption that their production is ad hoc and therefore cannot be described in systematic terms. Inspired by the dramatic advances in Deep Neural Networks (DNNs) MaPPLexiC considers a lexical collocation identification and classification DNN as a cognitive model, whose internal neuron activation vectors during the assessment of the collocation status of a given word combination can be translated into interpretable semantic, contextual, and socio-cultural features of the collocation elements and generalized into “collocation production principles” that dictate which features lexical items must possess to form a lexical collocation. In other words, what MaPPLexiC targets is a lexical collocation grammar. For this purpose, the Project will adapt and advance state-of-the-art techniques for the derivation of interpretable features from DNN’s activation vectors of individual lexical collocation samples and neural clustering techniques that will facilitate the generalization of the obtained “profiles” for the individual samples to more generic collocation production principles. Considering that collocation construction differs from language to language, the Project has a strong multilingual orientation. The investigation will be carried out on pairs of Germanic (English, German), Romance (French, Spanish), Finno-Ugric (Finnish, Hungarian), and Slavic (Czech, Russian) languages. The collocation profiles of translation-equivalent collocation samples and the language-specific collocation production principles will be contrasted with the goal to develop cross-language collocation production transfer techniques, which will highly benefit collocationally under-resourced languages.

Leo Wanner – Barcelona Supercomputing Center (BSC)
AdG2024 –  SH4 – Social sciences & humanities – The Human Mind and its Complexity

Objective of the project:

How can we learn to live on earth in new ways? This is the challenge of the Anthropocene. We propose a novel 4Ps framework to investigate land–life dynamics, which, for the first time, will connect perspectives on human–nonhuman relations (Partners), property-making (Property), land regimes (Profit) and land–climate systems (Planet). We will draw on critical perspectives from both environmental humanities and agrarian studies, bringing together diverse traditions from human–nonhuman anthropology, geography, political ecology and economy, ecological economics and complex systems thinking in a unique interdisciplinary synthesis. Connecting land and life, this project will address four Anthropocene challenges – climate, biodiversity, food and infrastructure/investment – through four exemplar landscape cases in the Colombian Amazon, southern African savannas, Spanish Mediterranean plains and coastal Southeast Asia.

The core team (Borras, Corbera, Scoones and Tsing) bring a range of expertise and experience that, together with eight postdoctoral and seven PhD researchers, can form the foundation for radically rethinking how we conceptualise land–life relations in the Anthropocene. We have designed a collaborative project organisation and process for working together that will promote synergistic conceptual and methodological breakthroughs, while building the capacity of researchers to engage with Anthropocene challenges through a novel framework. Engaging with policymakers, social movements and local communities, our public action work will in turn lead to practical approaches to ‘landscape reform’, where new ways of living in the Anthropocene are imagined and elaborated.

Esteve Corbera – Institut de Ciència i Tecnologia Ambientals de la Universitat Autònoma de Barcelona (ICTA-UAB)
SyG 2025

Together with:

• Anna Tsing, Aarhus University, Denmark
• Ian Scoones, Erasmus University Rotterdam, The Netherlands
• Saturnino M. (Jun) Borras, Institute of Development Studies, United Kingdom

How magnetic fields interact with electrocatalytic performance

Electrochemistry and electrocatalysis are alternatives to fossil fuels, but their performance remains suboptimal. Studies suggest that magnetic fields can enhance these processes, though the underlying mechanisms remain poorly understood. The ERC-funded MAGNESIS project will explore how magnetic fields interact with electrocatalytic performance, from atomic-level studies to full-cell devices. It brings together experts in catalysis, surface science, magnetism, and theory to focus on water oxidation and carbon dioxide reduction. The project will validate structural, electronic, and magnetic factors that influence these reactions. By using both ex-situ and operando data, computational tools will clarify the mechanisms involved. Ultimately, it will advance electrocatalytic methods and pioneer the field of magneto-electrochemical science and technology.

Objective of the project:

In the last years, electrochemistry and electrocatalysis are increasing their impact across several fields. A major driving force comes from the promise of substituting current fossil-fuel powered thermal methods in the industry by electrochemical alternatives, driven by renewable electricity. However, electrochemical methods are still far from reaching the desired target performance. In this landscape, the recent discovery of magnetic fields enhancing electrocatalytic processes offers a plausible new strategy. The idea of boosting an electrocatalytic reaction by an external magnetic field becomes highly persuasive. Still, the origin of this phenomenon is hardly understood, given its complexity: dealing with a magnetic field, in an electric field, on a dynamic surface, during a chemical reaction is a multiple-body problem.

Our objective is to foster magneto-electrocatalysis by exploring rigorously the interplay between magnetic fields and electrocatalytic performance from atomic resolution in model systems up to full cell devices. This can only be achieved by a synergetic effort between experts in catalysis, surface science, magnetism and theory. We will focus on two relevant reactions: the spin-restricted water oxidation and the carbon dioxide reduction, both potentially spin-sensitive. Our aim is to validate the structural, electronic and magnetic key descriptors controlling this phenomenon, assessed by complementary ex-situ and operando data within the corresponding theoretical framework. Computational tools will consolidate the understanding and quantify the different mechanistic contributions to microscopic and macroscopic observations. The ambition with MAGNESIS is to define, in a rigorous way, the first principles and ultimate possibilities of magnetic fields in the development of advanced electrocatalytic methods, pioneering the novel field of magneto-electrochemical science & technology.

José Ramón Galán Mascarós – Institut Català d’Investigació Química (ICIQ)

SyG 2025

Together with:

• David Écija, Aarhus University, Denmark
• Jeppe Vang Lauritsen, IMDEA Nanoscience – Madrid Institute of Advanced Studies in Nanoscience, Spain
• Karsten Reuter, Max Planck Society, Germany

We propose a disruptive concept overcoming the fundamental limit of concurrently achieving specific, high-resolution imaging at depth in tissue. Our Zee-Zoom-Zap concept will serve as a one-stop-shop by combining early detection of cancer through small lumens (‘zee’), non-invasive “biopsies” (‘zoom’), and local therapy (‘zap’).
The main challenge in realising early detection of cancer is to overcome the fundamental limitation in concurrently achieving specific, high-resolution imaging at the cellular scale at depth in tissue. A radical departure from conventional optical biopsy concepts, our project employs a holistic approach to optical theranostics, with each research pillar constructed as an integral part of a unified concept. Four research fields, represented by four PIs, form its basis: cancer-specific phototheranostic probes, monolithically 3D-printed micro-optical catheters, complementary optical imaging methods for unprecedented range and sensitivity, lasers at wavelengths for both imaging and therapy, and novel physics-enhanced deep learning AI models for imaging, detection, decision support, and treatment guidance.

Based on an unmet medical need, the consortium will target pancreatic cancer. For decades, there has been little improvement in detecting and treating this cancer form. The long-term perspective for the Zee-Zoom-Zap is translation into the clinical setting as part of a combined population- and imaging-based screening workflow for early detection of pancreatic cancer and in situ treatment. The concept will be applicable to other cancers reachable through small lumens. The societal and economic impact, in terms of return on investment and increased survival rates, are envisaged to be significant. Furthermore, the project’s innovations, interdisciplinary character, and synergy are expected to lead to new ideas being conceived and the emergence and growth of new fields of research. The development of the Zee-Zoom-Zap concept is only the first step.

Miguel Ángel González Ballester – Universitat Pompeu Fabra (UPF)

SyG 2025

Together with:

• Andreas Kjær, University of Copenhagen, Denmark
• Ataman Çağlar, University of Freiburg, Germany
• Peter Eskil Andersen, Technical University of Denmark

Despite the spectacular success of the standard cosmological model over the past two decades, recent observations from large sky surveys and distance measurements with a broad range of cosmological probes suggest cracks to the accepted paradigm: differences now appear in measurements of quantities the current cosmological model predicts as equal. These are called “tensions”. The most important tension concerns the Hubble parameter, H0, which quantifies the expansion rate of the Universe now, some 13 billion years after Big-Bang. The Hubble tension is the discrepancy between the value of H0, when inferred as a global parameter of the standard cosmological model relying heavily on early-Universe physics, and when measured directly in the late-time Universe from the redshift-to-distance relation. While the tension is well-established, there is no consensus on its actual significance nor on what it means for the standard cosmological model, even broadly speaking. Comparing the values of H0 from the early and the late Universe is like “Threading a needle from the other side of the Universe”; in a very unique way it enables vital end-to-end tests of cosmology to be performed.

RedH0T proposes to determine, in a self-consistent manner and using the synergies between all available cosmological probes, whether the tension arises from observational issues or from limitations in the current cosmological model. In the former case, we will impose strong limits of possible deviations from the standard cosmological. But if the latter is confirmed, it will represent one of the most significant discoveries of the 21st century, with profound implications not only for cosmology, but also for physics in general. The team gathers all required expertise to tackle the problem from all view-angles, addressing in a self-critical and constructive way all theoretical and observational aspects simultaneously.

Licia Verde and Fréderic Courbin – Institut de Ciències del Cosmos – Universitat de Barcelona (ICCUB)

SyG 2025

Together with:

• Adam Riess, Johns Hopkins University, United States of America
• Julien Lesgourgues, Technical University of Aachen, Germany

The goal of SKIN2DTRONICS is to demonstrate the large scale integration (LSI, transistor count larger than 1000) of soft and thin (skin-like) electronic devices on ultra-flexible substrates, capable of conformally adapting to any rough and curved surface. This vision will be realized by atomically thin two-dimensional materials (2DMs) that possess compelling properties for this application: high electronic performance, environmental stability, low toxicity and cytoxicity, and extreme resilience to mechanical deformations.  With the increasing pressure towards ubiquitous electronics (wearables, Internet-of-Things, smart patches, etc.) it is urgent to develop electronics that can be easily integrated on the surface of everyday objects and, in the case of health monitoring applications, on a variety of rough biological surfaces. Today’s conformal electronics is mainly based on conformal sensors with flexible and stretchable electrodes interfaced to bulky silicon chips, responsible for processing. This approach is prone to mechanical failures, especially at the solderings, as the connection between the conformal and solid components remains very challenging.  The research will rely on the complementary conjuncture of four fields: sensors, 2D-based electronics, flexible electronics and biomedical engineering that the PIs of the consortium bring, each of them recognized experts in their respective fields and with a valuable experience in leading ERC projects.

Kostas Kostarelos – Institut Català de Nanociència i Nanotecnologia (ICN2)
SyG 2024

Together with:

• Gianluca Fiori, Università di of Pisa, Italy
• Andrés Castellanos-Gómez, Insntituto de Ciencias de Materiales de Madrid (ICMM – CSIC), Spain
• Andres Kis, École Polytechnique Fédérale de Lausanne (EPFL), Switzerland 

Bioinks to support multiphasic models

Bioinks are materials that hold and protect cells during bioprinting while providing a supportive extracellular environment. They must be biocompatible and mimic the extracellular matrix to enable effective cell functions. Current bioinks cannot reliably retain growth factors. However, a new class of bioinks incorporates ECM proteins, such as fibronectin and laminin, into a hydrogel matrix, thereby enhancing the printing process. The ERC-funded FACTORINK project will harness the potential of bioinks by demonstrating their ability to support multiphasic models comprising stem cells, endothelial cells, and immune system components. The findings will contribute to defining the commercial pathways for these products, ultimately leading to the development of new intellectual property.

Objective of the project:

Bioinks are materials that hold cells during bioprinting. They perform key functions, including protecting cells from high shear stress during the printing process but also, and importantly, provide the extracellular environment for cells after printing. Bioinks must be made of biocompatible materials that in addition should provide the functional environment needed for cells to perform their functions. This is critical as bioprinting underpins developments of in vitro tissue models to advance biomedical research and drug testing. The functionality of bioinks must recapitulate aspects of the extracellular matrix (ECM) and should include mechanical and biochemical considerations. For example, bioinks should result in constructs of well-defined rigidity as this influences processes such as stem cell differentiation or cancer progression. Also, bioinks must provide cells with controlled density of adhesion proteins and growth factors – this is key to induce relevant signalling pathways. Yet bioinks that are currently in the market are limited to basic adhesion peptides and lack the ability to retain growth factors that instead quickly diffuse out of the system after printing. We have recently developed a new class of bioinks that incorporate pegylated ECM proteins (like fibronectin and laminin) that are incorporated into a methacrylated-gelatin matrix without crosslinking, enabling an easy and robust printing process. We have started the patenting process for this technology together with CellInk, a Swedish company with a focus on bioprinting, and demonstrated the biological activity of the bioink using simple cell lines. Now, we want to unleash the potential of the bioinks by demonstrating their ability to hold multiphasic models containing stem cells, endothelial cells and the immune system. The data gathered through this application should help define the commercial route of the products and would lead to creating new intellectual properties.

Manuel Salmerón – Institut de Bioenginyeria de Catalunya (IBEC)
PoC – 2025

New treatment for brain tumours and metastases

Primary and metastatic brain tumours are challenging to treat due to limited therapeutic options and the inability of most drugs to cross the restrictive blood-brain barrier (BBB). Inhibition of the MYC oncogene appears to be a promising strategy against these tumours, but the only clinically validated direct MYC inhibitor to date, OMO-103, cannot cross the BBB. The ERC-funded SonoMYC project will combine OMO-103 with the SonoCloud technology developed by France-based Carthera, which uses ultrasound to temporarily disrupt the BBB. The combination proposed could establish a novel treatment for primary and metastatic brain tumours by enabling OMO-103 delivery to the brain. This synergy could address the growing demand for brain tumour therapies.

Objective of the project:

Brain tumours and brain metastases pose a significant therapeutic challenge due to limited treatment options, fatally linked to high morbidity and mortality. Treatment of these cancers is hindered by the presence of the blood-brain barrier (BBB), that restricts the free passage of molecules larger than 400 daltons, reducing the effectiveness of therapeutically impermeable compounds. While deregulation of the MYC oncogene is a main feature of these cancers, to date, effective and clinically-viable, BBB-permeable MYC inhibitors are lacking.

This project proposes to combine Omomyc (OMO-103), developed in our laboratory and the best characterized, direct MYC inhibitor, with Carthera’s SonoCloud technology, which temporarily disrupts the BBB using ultrasound. Omomyc is currently under clinical evaluation for other systemic aggressive cancers, under the sponsorship of Peptomyc, a spin-off from our lab, focusing on clinical application of our inhibitors. This new investigation will establish the feasibility and viability of its commercial development into a disruptive novel treatment for primary and metastatic brain tumours. This combination aims to enhance OMO-103 delivery to the brain, to improve its therapeutic efficacy and reducing any potential systemic side effects. The synergy between these technologies has the potential to generate new intellectual properties, facilitate technology transfers, and address a growing market for brain tumour therapies. By overcoming the BBB challenge and directly targeting MYC, this approach could significantly impact brain cancer treatment and create new commercial opportunities.

Laura Soucek – Vall d’Hebron Institut d’Oncologia (VHIO)
PoC – 2025

Light-powered microswimmers capture ‘forever chemicals’

Per- and polyfluoroalkyl substances (PFAS) are human-made chemicals known for lasting a long time in the environment. They also present serious health risks. Their common use in everyday products raises concerns, and traditional detection methods are slow and expensive. People can be exposed by consuming water containing PFAS. In this context, the ERC-funded PhotoSERS project aims to use light-driven microswimmers that can move through water to capture and detect PFAS. By combining spectroscopy with portable instruments, the system will provide real-time monitoring and consistent results. The project will design and test the microswimmer device to ensure it is practical and can be scaled up. Ultimately, the aim is to protect both ecosystems and human health.

Objective of the project:

Per- and polyfluoroalkyl substances (PFAS), commonly known as forever chemicals, are persistent organic pollutants of global environmental concern with serious health risks. Their extensive industrial use and toxic effects have led to the implementation of stringent regulations worldwide, highlighting the urgent need for more efficient and sensitive PFAS detection technologies. Current detection methods are often inefficient, time-consuming, and lack the sensitivity required for trace-level analysis and accurate identification. This project, PhotoSERS, aims to develop a molecularly imprinted microswimmer-based microfluidic chip for the simultaneous capture and detection of PFAS. These light-driven microswimmers will combine active motion with selective recognition capabilities, enabling efficient PFAS capture even in complex environmental water samples. Additionally, the system will combine Surface-Enhanced Raman Spectroscopy (SERS) detection with light-guided microswimmer self-assembly and a portable Raman spectrometer, enabling real-time, sensitive and reproducible detection of PFAS across different concentrations. Collaboration with industrial partners will ensure the industrial relevance of our technology by providing critical feedback on performance requirements, and supporting validation in real operational settings, ultimately accelerating its path to commercialization. Therefore, this innovative portable microswimmer-based device could contribute significantly to water monitoring technologies and environmental protection efforts by providing an efficient, field-deployable solution for PFAS capture and detection.

Katherine Villa – Institut Català d’Investigació Química (ICIQ)
PoC – 2025

Over the past two decades, the pharmaceutical industry has witnessed an exponential growth in approved covalent drugs. The majority of such drugs incorporate a chemical warhead, a mild electrophilic reactive functional group that forms covalent bonds in a reversible or irreversible manner with nucleophilic aminoacid residues. The aim of this proposal is to assess the viability of a new chemical warhead in the discovery of novel kinase inhibitors.

Marcos García Suero – Institut Català d’Investigació Química (ICIQ)
PoC – 2024

IRQUAL addresses the critical need for compact, integrated lasers operating in the short-wave infrared (SWIR) spectrum (1.3 2.5 m) for diverse applications such as consumer electronics, automotive, IoT, and AR/VR. Specifically, lasers in the eye-safe window (around 1.4 m and > 2 m) are crucial for LIDAR systems, 3D face recognition, and environmental monitoring. Current technologies, including solid-state lasers and III-V semiconductor laser diodes, face limitations in size, cost, performance and scalability. IRQUAL aims to develop a versatile heterogeneous-integrated laser platform. This platform will exploit SWIR CQD laser technology pumped by established GaAs-based high-power laser diodes to develop a device that covers the range 1.5 to 2.5 m. IRQUAL will further focus on the commercialization and exploitation of the technology described above. To achieve this aim, efforts will be made to develop a strong intellectual property portfolio and also engage with leading industrial figures that could assist in the development and validation of the technology. Achieving IRQUALs objectives will revolutionize SWIR light applications, enabling widespread use in automotive, mobile phones, machine vision, and sensing. Eye-safe illumination systems aligned with safety standards will further enhance commercial prospects. The technology’s low-cost and compatibility with consumer electronics laser technology will transform LIDAR, 3D imaging, and remote sensing, contributing to a significant socioeconomic impact. In essence, this project pioneers a new era in SWIR laser technology, introducing unprecedented compactness, cost-effectiveness, and scalability for a multitude of high-impact applications.

Gerasimos Konstantatos – Institut de Ciències Fotòniques (ICFO)
PoC – 2024

Arthritis, a widespread inflammatory condition, affecting millions globally, necessitates urgent advancements in therapeutic approaches. Predominantly characterized by osteoarthritis (OA), this debilitating condition causes joint pain and stiffness, notably impacting the knee, hand, and hip joints. OA, a chronic degenerative disease, intensifies with age, imposing a significant economic burden on healthcare systems. The insufficiency of current treatments highlights the need for innovative therapies. Tissue engineering and regenerative medicine offer promising avenues, with platelet-rich plasma therapy (PRP) emerging as a forefront contender. PRP harnesses the regenerative potential of growth factors (GFs) to stimulate tissue repair processes, particularly in cartilage and bone cells. However, clinical application faces hurdles, notably the rapid degradation of GFs within the intricate synovial fluid (SF) environment, limiting their therapeutic efficacy and distribution. To overcome these challenges, scientists explore advanced drug delivery systems utilizing nanoparticles (NPs) as carriers. Although promising, passive NPs diffusion through viscous biological barriers, such as joint fluids, remains a significant obstacle. In response, OrthoBots introduces enzyme-powered NPs, termed nanobots, as active carriers of GFs within SF. By utilizing enzymatic propulsion, nanobots aim to enhance GF transport and distribution, facilitating targeted cartilage regeneration. This innovative approach holds transformative potential, potentially revolutionizing arthritis therapy by overcoming current limitations and offering more effective and personalized treatment strategies. Through systematic in vitro studies and in vivo proof-of-concept demonstrations, OrthoBots will pave the way for the next generation of arthritis therapeutics, addressing the unmet clinical needs and improving patient outcomes.

Samuel Sánchez Ordóñez –  Institut de Bioenginyeria de Catalunya (IBEC)
PoC – 2024

Antibodies have become major players in the pharmaceutical industry and were valued at 0.16 US billion in 2023. Traditionally, antibodies are obtained after immunisation of different animals and then produced in relevant cells for use in research, diagnostics and therapy. In recent years, there is a growing public opinion in Europe to ban the use of animals for biomedical research, and therefore there is an increasing pressure to move from animal produced antibodies to design and produce them in vitro. Antibody engineering has another important advantage, which is the possibility of targeting a precise epitope and not rely on serendipity as when injecting an animal with an antigen. In recent years, there have been significant advances in protein design based on the use of artificial intelligence and precise force fields. Despite this, the majority of the companies that work on antibody design combine rational engineering with massive proprietary screening methods, and so far, there are no reported cases of fully de novo design of an antibody with nM affinity against a defined epitope. Using an interleukin receptor as a case study, we have shown that we can indeed fully design de novo a nanobody that recognizes the target with nM affinity, using our proprietary protein design software FoldX and ModelX. Experts consulted to date indicate that the results obtained so far are truly impressive, prompting us to continue validating and optimising our process. Our proposal has two main objectives: First, to fully automate our pipeline that involves epitope selection, antibody framework selection and docking, backbone move and side chain search. Second, demonstrate that our optimised pipeline can design fully de novo nanobodies against a defined target in a fast and cost-effective way. Success in both objectives will open the way to fully de novo antibodies with desired properties, and position ourselves in the search for funding and spin-off incorporation.

Luis Serrano – Centre de Regulació Genòmica (CRG)
PoC- 2024

The fluctuating dynamics of living matter

Living matter is driven by energy-consuming microscopic processes like the action of molecular motors and cell division. These processes create active, non-equilibrium fluctuations that impact biological processes. However, unlike for thermal fluctuations, there is no theoretical framework for predicting active fluctuations. The ERC-funded LIVING_FLUCTUATIONS project aims to bridge this gap through theoretical research and experimental collaborations. First, at the subcellular scale, it aims to predict the active noise spectrum from the non-equilibrium binding kinetics of cytoskeletal proteins. Second, at the tissue scale, it aims to predict the statistical properties of pressure fluctuations due to stochastic cell proliferation. Ultimately, the project seeks to develop the stochastic hydrodynamics of living materials, shedding light on how active fluctuations drive biological functions in cells and tissues.

Objective of the project:

Living matter is active: It is driven far from thermodynamic equilibrium by irreversible microscopic processes, such as the action of molecular motors and cell division. This microscopic activity generates nonequilibrium fluctuations, which overwhelm thermal noise and impact biological processes across scales, from intracellular transport to tumour formation. However, unlike in the case of thermal fluctuations, we have no theoretical framework like the fluctuation-dissipation theorem to predict the statistical properties of active fluctuations. Here, I propose to address this knowledge gap by means of theoretical research combined with experimental collaborations organized in two aims.
In the first aim, at the subcellular scale, we will predict the spectrum of active noise based on the nonequilibrium binding kinetics of cytoskeletal proteins. To this end, we will coarse-grain a cytoskeletal network model in which detailed balance is explicitly broken at the molecular scale. We will then use the predictions to analyse experimental data and infer features of molecular activity in living cells and in the mitotic spindle.
In the second aim, at the tissue scale, we will predict the statistical properties of active pressure fluctuations due to stochastic cell proliferation, which is itself regulated by pressure. We will establish how this mechanical feedback affects the spectrum of the pressure field in a growing tissue. To this end, we will generalize tools from the renormalization group that were originally developed to study nonequilibrium critical phenomena through the Kardar-Parisi-Zhang equation. We will then collaborate with experimentalists to test our predictions by measuring the spectrum of pressure fluctuations in living tissues for the first time.
Overall, this research will lay the basis of a stochastic hydrodynamics of living materials and, at the same time, reveal how active fluctuations promote biological functions in cells and tissues.

Ricard Alert – Universitat Barcelona (UB)
StG2023 – PE3 – Physical sciences & engineering – Condensed Matter Physics

Investigating the dynamic behaviour of smart polymer materials using mechanochemical methods

Smart polymers, also known as stimuli-responsive polymers, are high-performance materials that change in response to their environment. It takes a small variation in temperature, light or other parameter to induce a large change in the behaviour of such materials. The EU-funded ReHuse project will focus on inducing a change in the behaviour of smart polymers using mechanical strength, which has been hitherto neglected. Project work will be geared towards inducing changes in the properties of bulk materials isothermally and reversibly by applying mechanical forces. Researchers aim to mechanochemically activate covalent bonds in bulk polymers by applying reversible heterolytic mechanophores – molecular platforms that dynamically generate and recombine two oppositely charged (macro)molecular fragments upon mechanical stimulation.

Objective of the project:

Stimuli-responsive polymers adapt their properties in response to external cues. Engineering such “smart” behaviour in artificial systems by molecular design is an exciting fundamental challenge that can lead to technological breakthroughs. Most stimuli-responsive polymers rely on heat and light to trigger changes in materials properties in a predictable fashion. However, limitations intrinsic to these stimuli highlight the necessity of alternative strategies. Naturally evolved systems widely exploit mechanical stimulation to regulate their functions, but recreating such concept in artificial materials has proven extremely challenging thus far.

ReHuse proposes a radically new approach that focuses on the application of mechanical force to induce changes in bulk materials properties isothermally and reversibly. The research project aims at pushing the frontiers of covalent mechanochemistry through the development of reversible heterolytic mechanophores –molecular platforms that dynamically generate and recombine two oppositely charged (macro)molecular fragments upon mechanical stimulation. These new motifs will enable dynamic chemistries involving organic ionic species in solid-state systems in two different types of advanced bulk materials. Combining reversible mechanochemistry and dynamic covalent chemistry will lead to dynamic covalent polymers displaying selective mechanoresponsiveness. This concept will be leveraged to create recyclable materials. The reversible generation of charges from the heterolytic scission will enable to modulate hydrophilicity/hydrophobicity dynamically. Such principles will be explored to set the groundwork for mechano-responsive atmospheric water harvesters. This interdisciplinary research project will advance our understanding of mechanochemistry and, more importantly, will usher new avenues for its productive and repeatable use in adaptive materials.

José Augusto Berrocal – Institut Català d’Investigació Química (ICIQ)
StG2021 – PE5 – Physical sciences & engineering – Synthetic Chemistry & Materials

While it is sometimes suggested that we are living in a ‘post-truth’ age wherein the concept of truth is increasingly less relevant, truth nonetheless remains a central concept in science, ethics, and ordinary life. However, what precisely is truth? One common view, the so-called ‘correspondence theory of truth’, maintains that truth is simply correspondence with the facts. However, such a view faces a number of difficulties and potential objections. For instance, what exactly is correspondence? And what exactly are facts? Moreover, if truth is simply correspondence then why it is the case that correspondence comes in degrees whereas truth is usually agreed not to? And how should we deal with certain semantic paradoxes, such as liar paradoxes, which suggest that our conceptions of truth are internally inconsistent?
The notion that truth consists in correspondence goes back to antiquity and the Middle Ages. However, although past philosophers discussed the nature of truth in significant detail and with considerable philosophical sophistication, our understanding of past theories of truth is surprisingly limited and we lack a clear idea of how notions of truth developed in later antiquity or in the Arabic and Latin medieval traditions. This project will offer the first focused and systematic examination of philosophical conceptions of truth in ancient and medieval philosophy. It will examine the origins, motivations, and challenges faced by conceptions of truth in this period and how these challenges led to the development of alternative theories of truth. By holistically examining both ‘major’ and ‘minor’ figures and texts in this period and combining metaphysical approaches to truth with logical and semantic approaches, this project will offer us a better understanding of a central philosophical issue across the Greek, Arabic, and Latin traditions and greater insight into an extremely rich but often neglected period of philosophy.

Tamer Nawar – Universitat de Barcelona (UB)
StG2021 – SH5 – Social sciences and humanities – Cultures & Cultural Production

Scaling up theoretically sound reinforcement learning

Reinforcement learning (RL) is a subfield of machine learning concerned with how intelligent agents interact with unknown environments to maximise their rewards. The potential application of RL techniques on challenging real-world problems, such as autonomous vehicle control or smart energy grids, has brought significant attention to the field. However, state-of-the-art RL algorithms are not applicable in the most promising domains, largely due to the lack of formal performance guarantees. The EU-funded SCALER project aims to address this challenge by taking a principled approach to developing a new generation of provably efficient and scalable reinforcement learning algorithms. The methodology will be based on identifying novel structural properties of large-scale Markov decision processes that enable computationally and statistically efficient learning.

Objective of the project:

Reinforcement learning (RL) is an intensely studied subfield of machine learning concerned with sequential decision-making problems where a learning agent interacts with an unknown reactive environment while attempting to maximize its rewards. In recent years, RL methods have gained significant popularity due to being the key technique behind some spectacular breakthroughs of artificial intelligence (AI) research, which renewed interest in applying such techniques to challenging real-world problems like control of autonomous vehicles or smart energy grids. While the RL framework is clearly suitable to address such problems, the applicability of the current generation of RL algorithms is limited by a lack of formal performance guarantees and a very low sample efficiency. This project proposes to address this problem and advance the state of the art in RL by developing a new generation of provably efficient and scalable algorithms. Our approach is based on identifying various structural assumptions for Markov decision processes (MDPs, the main modeling tool used in RL) that enable computationally and statistically efficient learning. Specifically, we will focus on MDP structures induced by various approximation schemes including value-function approximation and relaxations of the linear-program formulation of optimal control in MDPs. Based on this view, we aim to develop a variety of new tools for designing and analyzing RL algorithms, and achieve a deep understanding of fundamental performance limits in structured MDPs. While our main focus will be on rigorous theoretical analysis of algorithms, most of our objectives are inspired by practical concerns, particularly by the question of scalability. As a result, we expect that our proposed research will have significant impact on both the theory and practice of reinforcement learning, bringing RL methods significantly closer to practical applicability.

Gergely Neu – Universitat Pompeu Fabra (UPF)
StG2020 – PE6 – Physical sciences & engineering – Computer Science & Informatics

Diet-based regulation of sperm RNA

Emerging evidence underscores the importance of environmental factors such as stress, diet and toxins on the epigenetics of mammalian sperm. RNA is considered to carry such epigenetic information across generations and regulate the metabolic health of offspring. Funded by the European Research Council, the EpiSperm project aims to delineate the RNA modifications that affect RNA transcriptomic and epigenetic dynamics in sperm using a novel sequencing technology. Researchers will obtain a holistic view on RNA dynamics at the single-cell level. Moreover, they will unveil candidates that can transmit diet-induced paternal phenotypes to the next generation.

Objective of the project:

Mammalian sperm RNA is increasingly recognized as an additional source of paternal hereditary information beyond DNA. Environmental inputs, such as diet and stress, can reshape the sperm RNA signature and induce offspring phenotypes that relate to paternal environmental stressors. However, how, when and to what extent sperm RNA populations change, and what is the role that RNA modifications and other post-transcriptional regulatory layers play in shaping sperm RNA dynamics, remains poorly understood. Here, we propose to characterize the dynamics of RNA populations during sperm formation and maturation using native RNA nanopore sequencing. This technology is suited to provide an integrative and comprehensive view of the transcriptome, epitranscriptome, degradation patterns and tailing dynamics simultaneously, and with single molecule resolution. We will establish novel library preparation methods that can capture the full sperm (epi)transcriptome, and will capitalize on our recently developed algorithms to map and quantify RNA modifications in individual RNA molecules. We will then apply these methods to reveal how paternal dietary exposures affect sperm RNA populations and the metabolic phenotypes of their offspring, and test whether the novel identified RNA candidates can transmit diet-induced paternal phenotypes to the subsequent generation. Finally, we propose to expand our previous work on direct RNA multiplexing to establish single cell direct RNA nanopore sequencing, to characterize the diversity and heterogeneity of the sperm RNA (epi)transcriptome at an unprecedented single cell and single molecule resolution.

Eva María Novoa – Centre de Regulació Genòmica (CRG)
StG2021 – LS2 – Life Sciences – Integrative Biology: From Genes & Genomes to Systems

Helping computers comprehend human language

Natural language understanding (NLU) is a branch of artificial intelligence (AI) that uses computer software to understand input made in the form of sentences in text or speech format. Think of Siri answering a question about what the traffic is like this morning or Alexa asked about the weather in your city. In other words, NLU digests a human text, translates it into computer language and produces an output in human language. NLU applications have unique information needs and require large collections of annotated data to achieve good results. The EU-funded INTERACT project will develop new interactive learning algorithms (ILA), motivated by applications in NLU. It will merge representation learning and active learning of compositional latent-state models (CLSMs) since natural language is rich, complex and compositional.

Objective of the project:

INTERACT will develop new Interactive Learning Algorithms (ILA), motivated by applications in Natural Language Understanding (NLU). The main assumptions behind supervised approaches are unrealistic because most NLU applications have unique information needs, and large collections of annotated data are necessary to achieve good performance. INTERACT follows a collaborative machine learning paradigm that breaks the distinction between annotation and training. We focus on compositional latent-state models (CLSMs) because natural language is rich, complex and compositional. To reduce the amount of human feedback necessary for learning CLSMs we must eliminate annotation redundancy. We argue that to achieve this in the context of CLSMs we must combine: (1) An optimal human feedback strategy, with (2) inducing a latent structure of parts in the compositional domain. Annotation effort will be minimized because the method will only request representative feedback from each latent class. INTERACT marries representation learning (i.e. of parts) and active learning for CLSMs.

Our approach goes beyond classical active learning where the ILA asks labels for samples chosen from a pool of unlabeled data. We empower the ILA with the ability to ask for labels for any complete or partial structure in the domain, i.e. the ILA will be able to generate samples.

We work under the framework of spectral learning of weighted automata and grammars and use ideas from query learning. A key idea is reducing the problem of interactive learning of CLSMs to a form of interactive low-rank matrix completion. Our concrete goals are: (1) Develop ILAs for CLSMs based on spectral learning techniques; and (2) Investigate optimal strategies to leverage human feedback, taking into account what is optimal for the ILA and what is easy for the teacher.

We will experiment with NLU tasks of increasing complexity, from sequence and tree classification to parsing problems where the outputs are trees.

Ariadna Quattoni –  Universitat Politècnica de Catalunya (UPC)
StG2019 – PE6 – Physical sciences & engineering – Computer Science & Informatics

Hematopoiesis has long been modeled as a stepwise hierarchical process, where all blood cells arise from a single group of rare multipotent stem cells. For decades, various reports have contested this unifying paradigm, indicating that hematopoietic stem cells are functionally heterogeneous and differ on the rates and types of blood cells that they produce. However, the origins of stem cell heterogeneity and, importantly, its physiological consequences have remained ambiguous. My recent research suggests that individual stem cell behaviors are deterministic and programmed through long-lasting epigenetic memories, but how these different stem cell memories arise during development or injury is currently unknown. Intriguingly, my preliminary results indicate that stem cell memories instruct not just their fate decisions but also the functional properties of their mature progeny, thus raising the question of how stem cell memories create functional patterns that bias the cellular responses of their mature progeny.

Thus, the objectives of MemOriStem are: (1) to uncover the mechanisms that establish the diversity of HSC memories during development; (2) to identify the molecular determinants that maintain specific HSC properties; and (3) to characterize how developmental and acquired HSC memories determine functional patterns in mature blood cell responses. To overcome various challenging aspects of studying cell memories in vivo, I have designed a ground-breaking approach that combines innovative mouse models for transient gene silencing, multiplexed clonal analysis, and molecular recorders of cellular states.

In sum, MemOriStem will precisely define the origins, mechanisms, and physiologic consequences of hematopoietic memories, thus allowing a conceptual leap forward in regenerative and stem cell biology. Harnessing the programming of stem cell memories may help in the development of in situ cell therapeutics to treat chronic inflammation, aging, and cancer.

Alejo Rodríguez-Fraticelli – Institut de Recerca Biomèdica de Barcelona (IRB Barcelona)
StG2021 – LS3

Cell types are the fundamental units of animal multicellularity. Distinct cell types are established and maintained by specific gene regulatory networks (GRNs), as well as epigenomic mechanisms that mediate the asymmetric access to genetic information within each cell. This cell regulation results in complex metazoan functions and structures. However, cell types and their regulation have only been characterized in a few species. Therefore, the origin and evolution of animal cell types remain largely unexplored, and so remains the evolution of the underlying GRNs and epigenomic mechanisms.
In this project, we will develop a unified comparative framework to study cell type evolution and regulation from a multi-level and phylogenetic perspective. This project will focus on non-bilaterian metazoan lineages (Porifera, Ctenophora, Placozoa, and Cnidaria) as they are maximally informative towards reconstructing the evolutionary origins of metazoan genome regulation and of major cell types and their GRNs (e.g. neurons, secretory cells, stem cells, epithelial cells). To this end, we will integrate single-cell genomics and epigenomic profiling methods with advanced computational tools in order to: (1) investigate the origins of the animal regulatory genome; (2) characterize the diversity of cell type programs in non-bilaterian metazoans; and (3) model the structure and evolutionary dynamics of cell type-specific GRNs in these lineages.
This evolutionary systems biology approach provides a complementary angle to both phylogenetically-restricted single-cell analyses and traditional cross-species studies based on targeted marker genes. Therefore, our results will fill a large gap of knowledge in our understanding of the origin and diversification of animal cell type programs and epigenomic mechanisms. In a broader context, this research program will provide unprecedented insights into the fundamental question of how cell types and their defining regulatory networks evolve.

Arnau Sebé Pedrós  – Centre de Regulació Genòmica (CRG)
StG2019 – LS8

Autonomous photo-rechargeable nanoswimmers that keep moving and functioning in the dark

Inspired by nature, researchers can design tiny devices that take up energy from their surroundings and transform it into motion, mimicking natural microswimmers. However, current photoactive nanoswimmers require constant energy input to keep their functionalities, which limits their applicability in specific environments (e.g. non-scattering conditions). The ERC-funded PhotoSwim project will design hybrid nanoswimmers consisting not only of photocatalytic but also luminescent materials. These materials will enable the photoactivated swimmers to store and emit sufficient energy to keep working in the absence of constant light irradiation and exhibit long-term luminescence for tracking purposes. Researchers will investigate how to programme the nanoswimmer motion activation in the dark by modulating the energy/charge transfer among components.

Objective of the project:

The realization of smart nanoswimmers capable of moving and performing desired tasks in an aqueous environment is a technological challenge due to the viscous and thermal forces exerted upon them. While various types of external stimulus can be used to activate their autonomous motion, light is the easiest to operate and most flexible, due to the opportunities that it offers for motion modulation through intensity, wavelength, and direction. However, such optical control is affected by the properties of the aqueous media, limiting the applicability of light-driven nanoswimmers to non-scattering environments. The novel approach of this project (PhotoSwim) is the design of hybrid nanoswimmers that consist not only of photocatalytic but also persistent luminescent materials in order to provide triple light-responsive, light-storage, and light-emissive properties at the material level. This project will explore the potential of these innovative photoactivated swimmers to: (1) store and emit sufficient light energy to maintain motion in the absence of external irradiation, (2) exhibit long-term luminescence for tracking purposes, (3) move and interact with their surroundings at high speeds due to efficient charge pair separation and (4) achieve a major control over their motion by wavelength tunability. The knowledge obtained will then be used to expand the applicability of these hybrid nanoswimmers in scenarios of limited light penetrability. Specifically, their capabilities to maintain their photoactivity in the presence of chemical and biological interferences, along with real-time monitoring of their location by the emitted luminescence, will be tested. In this way, the potential of advanced multi-functioning nanoswimmers to keep moving and interacting with the surroundings in scenarios where the light supply is not fully available will be demonstrated.

Katherine Villa – Institut Català d’Investigació Química (ICIQ)
StG2022 – PE11 – Physical sciences & engineering – Materials Engineering

What were the cultural creations of black women and men in early modern Spain? How did blaWhat were the cultural creations of black women and men in early modern Spain? How did black women and men shape the cultural productions of the period? More than four hundred texts in early modern Spanish literature include black characters in a variety of literary genres, such as drama and poetry. The vast corpus of literary narratives on blackness has not fully engaged with the fact that Spain had the second-largest black African diaspora in early modern Europe —second only to Portugal— and that black women and men at that period were producers and contributors of cultural creations. With a focus on Spain and in connection with the Iberian World, BADEM will investigate three intertwined areas of Cultural History, Literature, and Linguistics, and provide a new scholarly framework to challenge our understanding of Europe’s past and its people. It will narrate an untold story of both the tangible and intangible cultural heritage that black Africans created, primarily but not exclusively as singers, dancers, actors, storytellers, and painters. It will explore the way black Africans refashioned and contributed to the production of early modern cultural narratives on blackness; and will investigate the African cultural traits and multilingual practices of black women and men, particularly in relation to their cultural mediations. In this way, BADEMS will promote an understanding of the experiences of survival through creativity, the making of blackness, and the processes of identity-building and creolization. The project will accomplish the goals in three domains of research: conducting the first systematic locating of black cultural creators; building a unique open-access Archive of Black Creators; and producing an interdisciplinary narrative about the contributions of black women and men to the literary, and linguistic culture of Spain in the sixteenth and seventeenth centuries.

Diana Berriezo-Sánchez – Universitat Autònoma de Barcelona (UAB)
CoG2021 – Social Sciences & Humanities (SH5 – Cultures & Cultural Production)

CAMP investigates long-term pastoral dynamics in drylands, by developing an innovative and reliable methodology to study archaeological pastoral sites. Pastoralism has been recently endorsed by the FAO as a successful strategy to achieve food security by efficiently exploiting the inherent variability in natural resources. Modern pastoral systems represent the legacy of animal domestication processes that started before the beginning of the Holocene. However, our understanding of ancient pastoralism is hampered by the lack of a proper methodology that can overcome the ephemeral evidence that characterize pastoral sites. CAMP will pavethe way, through methodological innovation, to a more thorough investigation of past adaptation to dryland environments. Highly controlled data on the anthropic markers for pastoral activities (chemical multi-element by portable X-Ray Fluorescence, phytoliths, organic residues and isotopes) will be collected in pastoral ethnographic settlements and analyzed to create models that will then be used to interpret the archaeological evidence. CAMP will advance research in: (a) methods and theory in the archaeology of pastoralism; (b) anthropic activity markers and the use of pXRF in archaeology; and (c) adaptive strategies in drylands. This project is a unique opportunity to strengthen the study of pastoralism by providing a widely applicable methodology that can augment our knowledge on past human adaptation to drylands and inform the design of sustainable and historically-grounded development strategies for pastoral futures. CAMP methodology will be potentially exportable to other archaeological sites, independently of their chronology, cultural or geographic context, representing an invaluable advance to archaeological methods at large.

Stefano Biagetti – Universitat Pompeu Fabra (UPF)
CoG2022 – (SH6 – The Study of the Human Past)

Cellular fitness maintenance in dormant oocytes

Female germ cells, oocytes, can survive for long periods while retaining the ability to create a new organism. The molecular mechanisms that allow oocytes to evade cellular ageing are poorly understood. The ERC-funded ACTIVEDORMANCY project aims to uncover the mechanisms behind the maintenance of cellular fitness and how these mechanisms are affected by ageing, employing imaging and state-of-the-art omics technologies. Oocyte dormancy involves at least two recently discovered unique mechanisms: the suppression of mitochondrial complex I and the constitutive activation of mitochondrial unfolded protein response. The current project will study the metabolic adaptations of cell survival without mitochondrial complex I, the long-lived oocyte proteins and their regulation, and the quality control mechanisms in dormant oocytes.

Objective of the project:

Female germ cells, oocytes, have the remarkable ability to survive for long periods of time, up to 50 years in humans, while retaining the ability to give rise to a new organism. We know surprisingly little about the molecular mechanisms through which oocytes alleviate cellular ageing, and why such mechanisms eventually fail with advanced age.

The goal of this research proposal is to reveal both the mechanisms dormant oocytes employ to maintain cellular fitness and how ageing affects these mechanisms, combining biochemical perturbations with imaging and state-of-the-art -omics techniques. We have recently discovered that oocyte dormancy involves two mechanisms not reported in any animal cell type before: the suppression of mitochondrial complex I, and the constitutive activation of mitochondrial unfolded protein response. These discoveries point to a set of poorly understood strategies that oocytes use to minimise damage to their cellular components during their long lifespan. In this project, we focus on three new interlinked directions to reveal mechanisms that dormant oocytes employ to keep a ‘youthful’ cytoplasm: 1) Characterise the metabolic adaptations that enable life without mitochondrial complex I 2) Study extremely long-lived oocyte proteins and their regulation 3) Identify and characterise the quality control mechanisms that eventually fail in dormant oocytes to impact fertility. We will use oocytes from frogs, mice, and humans which are complementary in their ease of handling and relevance to human physiology.

One of the biggest problems developed nations face is late-motherhood and associated fertility problems due to ageing oocytes. >25% of female fertility problems are unexplained, pointing to a huge gap in our understanding of female reproduction. This proposal will help fill this gap by studying longevity mechanisms in dormant oocytes. It will further provide insights into the metabolic adaptations of long-lived cells, female fertility, and ageing.

Elvan Böke – Centre de Regulació Genòmica (CRG)
CoG2022 – LS3 -Life Sciences – Cellular, Developmental & Regenerative Biology

ClimateAdapt – Adaptation to Climate Change in Developing countries

The fast pace at which the earth climate is changing is one of the major challenges of our time. Rising temperatures are expected to reduce agricultural productivity in developing countries, which face uncertain adaptation paths. The theoretical literature highlights two potential adjustment mechanisms: the reallocation of economic activity towards non-agricultural sectors or towards colder regions. In the first case, lower agricultural productivity generates a shift in comparative advantage towards non-agricultural sectors and a reallocation of workers from agriculture towards manufacturing and services. However, this path might not be feasible for regions with low manufacturing productivity. In this second case, the lack of local employment opportunities can lead to migration towards other areas. There is a rich theoretical and quantitative literature studying the relative importance of each margin of adjustment. However, these predictions are subject to a large level of uncertainty due to the lack of direct empirical evidence. In particular, we lack evidence on how labor and capital market frictions shape the adjustment to climate change. We are now in the position to produce this evidence. The last decade has been unusually hot, leading to many persistent extreme weather events in tropical countries, which triggered adaptation responses. In this project, we use newly digitized administrative reports on extreme weather events occurred in Brazil during the last two decades, a new meteorological measure of excess dryness relative to historical averages, and detailed social security and credit registry data to estimate the effects of climate change on i) the local economy of affected areas, ii) the magnitude of the labor and capital flows it generates and iii) factor allocation across sectors and firms in destination regions.

Paula Bustos – Institute for Political Economy and Governance (IPEG)
CoC2022 – Social Sciences & Humanities (SH1)

NEWSPIN – A New Spin on Quantum Atom-Light Interactions

A central goal of quantum optics is to realize efficient, controlled quantum interfaces between atoms and photons. Such interfaces enable broad applications from quantum information processing to quantum nonlinear optics to metrology, and also open a route toward creating exotic quantum states of light and matter. Today, our major paradigm for realizing an efficient interface is based upon the concept of collective enhancement, where using a large number of atoms creates an enhanced coupling to a preferred optical mode over undesired emission into other directions. However, our known error bounds for applications decrease very slowly as a function of system resources, such as the optical depth, thus posing a great challenge for future technologies. In NEWSPIN, we propose a remarkable new way forward, based upon the realization that these conventional error bounds are derived without accounting for multiple scattering and wave interference between emitting atoms. We aim to establish that interference in light emission is in fact a much more powerful resource than the level that we currently exploit it. In particular, beyond the usual collective enhancement, it can simultaneously enable a much stronger collective suppression of emission into undesired directions, and which can yield exponentially better error bounds than was previously known. Underlying this powerful paradigm shift will be the development of a quantum many-body theory of multiple scattering involving photons and atoms, which takes advantage of state-of-the-art tools from condensed matter physics. Beyond robust new routes toward applications, our theory will also reveal exotic new quantum phenomena and lead to new insights into fundamental questions in optics, such as the physical limits to how large the refractive index of an optical material can be. In total, we anticipate that NEWSPIN could greatly enrich our understanding of atom-light interactions and their realm of possibilities.

Darrick Chang – Institut de Ciències Fotòniques (ICFO)
CoC2020 – Physical Sciences & Engineering (PE2)

LArcHer – Breaking barriers between Science and Heritage approaches to Levantine Rock Art through Archaeology, Heritage Science and IT

LArcHer project aims at pioneering a new and more comprehensive way of understanding one of Europe’s most extraordinary bodies of prehistoric art, awarded Unesco World Heritage status in 1998: Levantine rock art (LRA). The ground-breaking nature of the project relies on combining a multidisciplinary (Archaeology, Heritage Science and IT) and multiscale approach (from microanalysis to landscape perspectives) to gain a holistic view of this art. It also aims at closing existing gaps between science and heritage mainstreams, to better understand the values and threats affecting this tradition and bring about a change in the way we understand, care, use and manage this millenary legacy. LArcHer aims are: a) Use cross-disciplinary knowledge and methods to redefine LRA (i.e. new dating techniques to refine chronology, new analytical methods to understand the creative process); b) Use LRA as a proxy to raise new questions of global interest on the evolution of creative thinking and human cognition (i.e. the timing and driving forces behind the birth of anthropocentrism and visual narratives in the history of prehistoric art); c) Develop new research agendas to set off complementary goals between science and heritage and define best practices for open air rock art conservation and management.

Spread across Mediterranean Iberia, LRA is the only European body of figurative art dominated by humans engaged in dynamic narratives of hunting, violence, warfare, dances and so forth. These scenes are unique to explore past social dynamics, human behaviour and cultural practices. As such, it is the only body of European rock art with potential to answer some of the new questions raised by LArcHer.

Key to LArcHer are the systematic recording and analysis of the art through 3D Digital technologies, management and data storage systems, GIS, physicochemical analysis of pigments and bedrock and comparative analysis with other major bodies of art with equivalent developments.

Inés Domingo – Universitat de Barcelona (UB)
CoG 2018 – Social Sciences & Humanities (SH6)

ATOMISTIC – Atomic-Scale Tailored Materials for Electrochemical Methane Activation and Production of Valuable Chemicals

Electrochemical methane activation and direct conversion to methanol is highly attractive – a dream reaction that would convert a greenhouse gas into a valuable liquid fuel in a dream device, on-site, and powered by renewable electricity. However, sustainable C-H activation and direct methane to methanol conversion at ambient conditions remain as great fundamental challenges.
My aim with ATOMISTIC is: (i) to develop new methods for electrochemical methane activation and partial oxidation, (ii) to control the structure of the electrochemical interface and the catalytically active site, in order to tune selectivity for the synthesis of valuable fuels and chemicals (such as methanol) from methane, and dimethyl carbonate from methanol. I will use 3 main strategies:
– To establish the ideal structures and electrolytes, using well-defined tailored materials that enable methane activation by its direct adsorption on the electrode material.
– To realise advanced materials that enable the indirect electrochemical activation of methane through the generation of solution phase radicals.
– To tailor the active site at the atomic level for selective methane to methanol and methanol to dimethyl carbonate oxidation reactions on functional materials.
I will elucidate the design principles and unveil the structure-reactivity-selectivity relations and the molecular mechanisms of these reactions as well as the atomic-scale structure of the catalyst materials. I will achieve these ambitious goals by leveraging my work combining the insight from model studies with experiments under realistic conditions to discover new materials. I will combine electrochemical methods, electrochemical scanning probe microscopy, in situ optical spectroscopy, online mass spectrometry and operando synchrotron-based x-ray techniques. The success of ATOMISTIC will result in significant breakthroughs in the fields of chemistry and catalysis, opening up new sustainable ways to produce valuable chemicals.

Maria Escudero – Institut de Ciències de Materials de Barcelona (ICMAB-CSIC)
CoG 2021 – Physical Sciences & Engineering (PE5)

ReSinAge – Regeneration of Sinusoidal niches to preserve hematopoiesis after chemotherapy on Ageing

Cancer is a disease of the elderly and chemotherapy remains the mainstay of treatment. The benefits of chemotherapy include increased overall survival, improvement in quality of life, and palliation of symptoms. However, older patients are more susceptible to specific toxicities of chemotherapy, like myelosuppression and life-threatening neutropenia.
Among the tissues strongly affected by chemotherapy, the bone marrow sinusoidal endothelial cells constitute the most important supportive niche for aged hematopoietic stem cells function and for myelopoietic recovery in the elderly. Up to now, few data are available about how aged sinusoidal niches regenerate upon chemotherapy damage and whether it is possible to rejuvenate vascular endothelial stem cells and improve the regeneration of the old sinusoidal niche as an effective strategy to improve HSC function and prevent myelosuppression and life-threatening neutropenia in the elderly.
Here I hypothesize that the reduced regenerative capacity of aged sinusoidal niches can be improved by rejuvenating vascular endothelial stem cells in vivo via targeting Cdc42 activity and the Notch:Jag2 signaling. The current proposal investigates whether improving the regeneration of the aged sinusoidal niche might represent an important target to enhance the hematopoietic recovery and increase the survival after chemotherapy in the elderly.
By combining several ground-breaking approaches ranging from single-cell sequencing, whole-mount bone marrow imaging, deep learning strategies for data analysis and integration, stem cell sorting techniques and specific mouse models, this research project will demonstrate that aging is not irreversible and that targeting the stem cell niche could represent an unprecedented innovative strategy to improve the regenerative capacity not only of hematopoietic stem cells.

Maria Carolina Florian – Instituto de Investigación Biomédica de Bellvitge
CoG 2020 – Life Sciences (LS4)

Quasar spectroscopic data could shine light on fundamental cosmological problems

How does dark energy cause the expansion of the universe to accelerate? Were initial conditions in the universe set by cosmic inflation? How much do neutrinos weigh? These open questions at the boundary of cosmology and fundamental physics can be addressed by studying the distribution of matter in the universe, as a function both of scale and of time. Until now, the traditional approach has been to use large galaxy catalogues. The EU-funded COSMO-LYA project will use an alternative probe: the Lyman-α (Lyα) forest, absorption features in the spectra of high-redshift quasars caused by neutral hydrogen. The Lyα forest could provide a unique window to study the distribution of matter at earlier times and on smaller scales than those accessible with galaxy catalogues.

Objective of the project:

Key open questions in the boundary of cosmology and fundamental physics can be addressed by studies of the distribution of matter as a function of scale and time (or redshift). While the traditional approach has been to use large galaxy catalogues, during the last decade I have pioneered the use of an alternative probe: 3D correlations in the Lyman-α (Lyα) forest, absorption features in the spectra of high-redshift quasars caused by intervening neutral hydrogen. The Lyα forest provides a unique window to study the distribution of matter at earlier times and on smaller scales than those accessible with galaxy catalogues.
I lead the Lyα analysis of the Dark Energy Spectroscopic Instrument (DESI) survey, and with ERC support I will be able to develop and apply new techniques to dramatically enhance its expected outcome. On one hand, COSMO-LYA we will use the correlations on large (> 30 Mpc) scales to obtain a 0.5% measurement of the expansion rate of the Universe at z > 2, four times better than the state-of-the-art.
On the other hand, we will carry out the first coherent analysis of 1D and 3D correlations to provide a 1% measurement of the amplitude of density fluctuations on small (~1 Mpc) scales, unreachable by other probes. In combination with public CMB results, sensitive to the distribution of matter at early times and on the largest scales, we will be able to construct a cosmological lever arm covering 4 orders of magnitude in scale. This will enable my team to: i) increase by at least a factor of 2 the constraints on the sum of the neutrino masses, potentially leading to the first measurement of the absolute neutrino masses; ii) increase by at least a factor of 3 our constraints on the shape of the primordial power spectrum of density fluctuations, an important step towards confirming or falsifying a large number of inflationary models. These results will have interdisciplinary impact, with wide reaching consequences into particle and fundamental physics.

Andreu Font – Institut de Física d’Altes Energies (IFAE)
CoG2021- PE9 – Physical Sciences & Engineering – Universe Sciences

The major goal of this application is to develop the catalytic generation of conceptually-novel carbyne equivalents and related species, and to study their reactivity towards organic matter. The catalytic activation of designed sources will reveal new reactivity rules at carbon that have been missing, not only in the design and discovery of new chemical reactions, but also in their use to build molecular complexity. Our approach will rely on novel activation modes that unlock elusive and useful tools for molecular editing.

Marcos García Suero – Instituto Català d’Investigació Química (ICIQ)
CoG 2019 – (PE5 – Synthetic Chemistry & Materials)

CRISPR development has enormously accelerated genetic engineering principles, and precise methods to modify small alleles (such as base or prime editing) are now available. However, generating large genomic changes still presents enormous challenges. Large modifications, such as gene transfers, are performed generally with viral vectors, which have been associated with toxicities in the clinic, and often lack versatility needed for basic science experimentation. Newer CRISPR-based techniques for gene transfer suffer from significant efficacy and safety problems when used for large message writing.

The overall goal of SCRIBE is to create new strategies for gene writing and define their molecular principles. These new writers will use RNA to both encode and transfer the message. The SCRIBE strategies will take advantage of the retrotransposon capacity for writing genes from RNA, and the precision of CRISPR in addressing specific sites of the genome. Thus, the “find” function will be dominated by CRISPR components, and “copy-paste” activity will be executed by retroelement components. To develop and optimize such a technology, we will use evolutionary analysis to select those retroelements with the highest activity and orthogonality, and modulate their message writing capacity by engineering their components. We will test various CRISPR and retrotransposon combinations, and adapt both of them to converge into a unified molecular machine. We will use artificial intelligence applied to protein design and a novel concept of synthetically oriented evolution to accelerate emergence of the new function. Finally, we will deploy new gene writing principles for RNA-based in vivo gene delivery.

In sum, we will develop a new family of tools for engineering life. The real breakthrough will be the establishment of gene writing as a simple and general method for both research advancement and applied purposes.

Marc Güell Cargol – Universitat Pompeu Fabra (UPF)
CoG 2022 – LS9

FOODCIRCUITS – Food Circuits: Hidden Connections between Migrants and Societies

Most fruit and vegetables required and enjoyed by European and North American societies would not be possible without the planting, harvesting and transporting performed by migrant labourers. Yet, the contribution of migrants to crucial food systems is generally hidden in the experience of buying and consuming food. In this project, I take asparagus from Germany, oranges from Spain and strawberries from California as the vantage points from which to see connections between migrants and societies as well as the ways in which those connections become invisibilized. I focus on embodied experiences in food circuits in order to understand the labour of producing and transporting food and the process of consuming and incorporating food into oneself. Tracing asparagus, oranges and strawberries through their circulation, I investigate the embodied experiences of migrant farm labourers – who are treated simultaneously as essential, disposable and sometimes prohibited; supply chain workers – who are made up increasingly of migrants and work under tight delivery time constraints; and consumers – who eat with diverse intentions of survival, enjoyment, identity and ethics. I propose a new way of seeing social and embodied connections between migrants and societies – through the beauty, brutality and necessity of food. With FOODCIRCUITS, I will provide novel contributions on three primary fronts:
(i) developing a theory of connections between migrants and societies – including on embodied levels – by following fruit and vegetables as they circulate from the hands that pick them, through the arms that deliver them to the mouths that eat them;
(ii) re-conceptualizing the ways in which indirect connections between different categories of people are invisibilized through the infrastructures and processes of producing, transporting and consuming food;
(iii) expanding collaborative methods and ethics in field research across steep social and power hierarchies.

Seth M. Holmes – Universitat de Barcelona
CoG 2021 – Social Sciences & Humanities (SH3)

NESTEDMICS – Regulatory and functional architecture of ‘Nested-Sensitivity’ microexon programs

Neural microexons are a paradigmatic example of a cell type-specific transcriptomic program. Microexons are tiny exons that we revealed to have striking neuronal specificity established by their master splicing regulator Srrm4, which activates them during neuronal differentiation. However, our unpublished data challenge this on/off regulatory and functional paradigm. We found that a related paralog, Srrm3, is lowly but significantly expressed also in endocrine pancreas and, together with Srrm4, configure a 3-step switch of Srrm3/4 activity in pancreas (low), brain (mid) and retina (high). These different levels of expression activate increasingly larger subsets of microexons in the three tissues, configuring a triple-nested microexon program. Remarkably, initial results support a model in which microexon subclass inclusion is dictated largely by their sensitivity to Srrm3/4, and each subclass is differentially enriched for distinct functional categories including vesicle-mediated transport, neuronal differentiation and cilium biogenesis. This project will assess the regulatory and functional architecture of this new paradigm by answering: (1) How are the different levels of the master regulators controlled in each cell type? (2) How are the distinct sensitivities of microexons to Srrm3/4 genomically encoded? (3) What are the functional implications of the ‘nestedness’ of the microexon programs? (4) How does misregulation of the nested programs contribute to disease? These goals will be achieved by a combination of high-throughput methods and focused experiments using in vitro and in vivo systems. The expected results will provide a transformative multi-level portrait of microexons, from quantitative regulatory logic to organismal functions. Moreover, this novel paradigm is likely to apply to many other master regulators, expanding the impact of the project and shedding new light into how cell type-specific transcriptomes are established in embryogenesis.

Manuel Irimia – Centre de Regulació Genòmica (CRG)
CoG2020 – Life Sciences (LS2)

INFRADOT – Mid- and Long-wave infrared Colloidal Quantum Dot Optoelectronics

Optoelectronics – sensing and light emission – in the mid and long-wave infrared (MWIR/LWIR) carry a very large informational dataset of our environment and has created a huge impact on safety and security, quality control, environmental monitoring, imaging, just to name a few sectors. To date, the available optoelectronic materials and technologies developed to serve this very important part of spectrum have been based on high cost and fragmented solutions, curtailing their introduction to a broad market use and unleash of their potential. INFRADOT will address this challenge by developing groundbreaking, lowcost, highly efficient material and device platforms operating in this so far under-exploited part of spectrum. In order to overcome the fundamental constraints arising from the bandgap of available materials, INFRADOT will lead to a paradigm shift in colloidal quantum dot (CQD) technology, by making a leap from – the so far used – interband transitions to intraband transitions. In order to make efficient use of intraband transitions in CQDs, INFRADOT will address several fundamental challenges. It will: i) Make significant advances towards robust heavy doping schemes in CQDs, ii) Explore and control the intraband relaxation pathways by surface and quantum-dot structure engineering at the atomic scale, iii) Shed new insights on charge transport in heavily-doped, electronically coupled CQD films. Capitalizing on these advances and engineering the energetic potential landscape at the nanoscale in heterogeneous CQD and CQD-in-perovskite solids, INFRADOT will create new optoelectronic device architectures to harness efficiently intraband transitions for highly performant, low-cost photodetectors, light emitters and bolometers. The advances made in this project will lead to a new disruptive technology for the MWIR/LWIR, as well as provide extremely important directions in other fields that utilize hot carriers, for catalysis and energy harvesting applications.

Gerasimos Konstantatos – Institut de Ciències Fotòniques (ICFO)
CoG2020 – Physical Sciences & Engineering (PE8)

Artificial intelligence (AI) is widely regarded as one of the most promising and disruptive technologies for future healthcare. As AI algorithms such as deep neural networks are suited for the processing of large and complex datasets, radiology is the medical speciality that has seen some of the most important applications of AI in the recent years. However, despite these advances, a major limitation of current AI developments in medical imaging is that they have overwhelmingly, and almost entirely, targeted applications in high-income countries. There is a concern, if the current trend continues, that AI will increase the already pronounced inequalities in global health, in particular for resource-limited settings such as rural Africa, where the majority of the African population lives.

AIMIX will develop the first scientific framework for inclusive imaging AI in resource-limited settings. The project will greatly advance the current state-of-the-art, from existing AI methods mostly developed for high-income settings, towards new imaging AI algorithms that are fundamentally inclusive, i.e. (1) affordable for resource-limited clinical centres, (2) scalable to under-represented population groups, and (3) accessible to minimally trained clinical workers. Furthermore, AIMIX will investigate the socio-ethical principles and requirements that govern inclusive AI, and examine how they compare, conflict or complement those of trustworthy AI developed thus far in high-income settings. These innovations will be demonstrated for affordable and accessible AI-powered obstetric ultrasound screening by minimally trained clinicians such as midwives in rural Africa.

Ultimately, AIMIX’s scientific breakthroughs will enhance the democratisation of imaging AI in resource-limited settings, which will result in an important social impact, by empowering local communities, promoting inclusion, and reducing disparities between populations from low- and high-income societies.

Karim Lekadir – Universitat de Barcelona (UB)
CoG2021 – Life Sciences (LS7 – Prevention, Diagnosis & Treatment of Human Diseases)

ApeGenomeDiversity – Great ape genome variation now and then: current diversity and genomic relics of extinct primates

In our quest to fully understand the processes that shape the genomic variation of species, describing variation of the past is a fundamental objective. However, the origins and the extent of great ape variation, the genomic description of extinct primate species and the genomic footprints of introgression events all remain unknown. Even today, and in contraposition to human evolutionary biology, the almost null presence of ancient great ape samples has precluded a comprehensive exploration of such diversity.

Here, I present two approaches that will expose great ape diversity throughout time and will allow me to compare the genomic impact of introgression events across lineages. First, I would like to take advantage of ancient ape samples that will provide us with a direct view of the genomes of extinct populations. Second, I would like to exploit current and recent diversity to indirectly access the parts of extinct ape genomes that became hybridized with current species in the past. For the latter, we will analyse hundreds of non-invasive samples taken from present-day great apes as well as historical specimens. Altogether, this information will enable me to decipher novel genomes that until now have been lost in time. In this way, I will be able to properly understand the origins and dynamics of genomic variants and to study how admixture has contributed to today´s adaptive landscape.

By completing this proposal and performing analogies to the human lineage, fundamental insights will be revealed about (i) the spatial-temporal history of our closest species and (ii) the functional consequences of introgressed events. On top of that, these results will help to annotate functional consequences of novel mutations in the human genome. In so doing, a fundamental insight will be provided into the evolutionary history of these regions and into human mutations with multiple repercussions in the understanding of evolution and human biology.

Tomàs Marquès – Institut de Biologia Evolutiva – Universitat Pompeu Fabra (IBE-UPF)
CoG2019 – Life Sciences (LS3)

ENGINORG – Engineering kidney organoids to study the interplay between Tissue Mechanics and Metabolism: from development to disease

Research with human pluripotent stem cells (hPSCs) has led to the development of miniorgan-like structures in culture, so called organoids. Generally, organoids are generated exploiting cell-autonomous responses of hPSCs with minimal control over the external inputs supplied to the system. The unrestrained nature of these approaches explains, in part, key shortcomings of the organoid technology, such as limited capacity to recreate all cell types within an organ, maturation and function. Data from my laboratory has shown, for the first time, that the presentation of a physical instruction (elastic modulus-stiffness) during the derivation of hPSCs-kidney progenitor cells results in the generation of hPSCs-kidney organoids with higher differentiation potential and functional attributes. Similarly, our preliminary results show that boosting metabolic activities differentially regulated upon the presentation of controlled physical cues represents a new strategy to generate specific kidney cells on demand. ENGINORG proposes conceptual and technical advances to mechanistically link how the presentation of controlled physical and metabolic constrains during organoid generation are integrated and resolved through gene expression regulation and epigenetics. To this end, we will combine micropatterning techniques, hPSCs-genome engineering, metabolomics, biomaterials design and microfluidics. The identification of the molecular mechanisms connecting how metabolic and mechanical cues modulate cell fate and function will define minimal design principles for the proper control of cell-cell and cell-matrix interplay, and cell organization for organoid generation. This knowledge will be implemented through three interconnected objectives to understand and model early steps of kidney morphogenesis and Congenital anomalies of the kidney and the urinary tract (CAKUT), which account for ~50% of the etiology of chronic kidney disease in children worldwide.

Núria Montserrat Pulido – Institut de Bioenginyeria de Catalunya (IBEC)
CoG2020- Life Sciences (LS9)

PHOTHERM – Photo Thermal Management Materials

Since the beginning of civilization, humanity has built houses to sustain comfortable living conditions throughout the seasons. In our modern society, about 50% of the total energy consumption is used for heating and cooling. Growing demands for thermal management in many different sectors, from electronics to housing, inevitably means increased energy consumption. The primary source of heat is coming from the combustion of fossil, bio, or waste-based feedstocks, all contributing to emissions. This project seeks to fundamentally change how we generate heating and cooling by developing a new class of materials that capture, store, and release both solar and ambient heat. The solar thermal management materials are a unique combination of molecular photo-switches that capture and store sunlight, so-called MOST systems, together with phase change materials (PCM) that can contribute to thermal management. The two classes of materials operate at fundamentally different principles. The input of MOST system is photons, whereas the output is heat. The PCM materials can absorb heat from the environment. By combining the two materials into one, we can harness and upgrade two of the most abundant renewable sources of energy on the planet: ambient heat and sunlight. The materials function will be demonstrated in heat to power devices that can operate 24/7 without the need for traditional batteries. The MOST-PCM combination has the potential to disrupt how we control the temperature in a broad range of applications, from local power production to heating and cooling in electronics systems, to temperature control in automotive and housing. The materials developed in this project have the potential to radically change thermal comfort and energy consumption and give new design opportunities to thermal management systems from the 10-9 to 10 m length scale.

Kasper Moth-Poulsen  – Institut de Ciència de Materials de Barcelona (CSIC – ICMAB)
CoG2020 – Physical Sciences & Engineering (PE5)

FASTEN – Fast yet accurate routine rational design of novel enzymes

Life could not be sustained without the presence of enzymes, which are responsible for accelerating the chemical reactions in a biologically compatible timescale. Enzymes present other advantageous features such as high specificity and selectivity, plus they operate under very mild biological conditions. Inspired by these extraordinary characteristics, many scientists wondered about the possibility of designing new enzymes for industrially-relevant targets. Unfortunately, none of the current enzyme design strategies is able to rapidly design tailor-made enzymes at a reduced cost. This is limiting the general routine application of enzyme catalysis in industry, and thus the chemical manufacturing competitiveness. The goal of this project is to develop a fast yet accurate computational enzyme design approach for allowing the routine design of highly efficient enzymes. FASTEN combines computational chemistry, deep learning, graph theory, and computational geometry for controlling the complexity of enzyme catalysis in a new computational protocol that will capture the chemical steps and conformational changes that take place along the catalytic itinerary. Active site and distal activity-enhancing mutations are predicted based on correlation and co-evolutionary-based guidelines, and the catalytic potential of the new designs is estimated by means of geometry-based oracles. This new computational approach will be validated with the design of enzymes presenting complex conformational dynamics and multi-step mechanisms. The experimental evaluation of many of the designs will finally reveal the potential of this new approach for the fast routinely design of industrially-relevant enzymes. FASTEN has the potential of making the routine design of enzymes possible, thus improving our current lives and leading to a more sustainable world for our generations.

Silvia Osuna  – Universitat de Girona (UdG)
CoG2022 – Physical Sciences & Engineering (PE4)

Pers_and_Preferences – Personality, Preferences, and Reference-Dependence

Since the beginning of civilization, humanity has built houses to sustain comfortable living conditions throughout the seasons. In our modern society, about 50% of the total energy consumption is used for heating and cooling. Growing demands for thermal management in many different sectors, from electronics to housing, inevitably means increased energy consumption. The primary source of heat is coming from the combustion of fossil, bio, or waste-based feedstocks, all contributing to emissions. This project seeks to fundamentally change how we generate heating and cooling by developing a new class of materials that capture, store, and release both solar and ambient heat. The solar thermal management materials are a unique combination of molecular photo-switches that capture and store sunlight, so-called MOST systems, together with phase change materials (PCM) that can contribute to thermal management. The two classes of materials operate at fundamentally different principles. The input of MOST system is photons, whereas the output is heat. The PCM materials can absorb heat from the environment. By combining the two materials into one, we can harness and upgrade two of the most abundant renewable sources of energy on the planet: ambient heat and sunlight. The materials function will be demonstrated in heat to power devices that can operate 24/7 without the need for traditional batteries. The MOST-PCM combination has the potential to disrupt how we control the temperature in a broad range of applications, from local power production to heating and cooling in electronics systems, to temperature control in automotive and housing. The materials developed in this project have the potential to radically change thermal comfort and energy consumption and give new design opportunities to thermal management systems from the 10-9 to 10 m length scale.

Antonio Penta  – Universitat Pompeu Fabra
CoG2022 – Social Sciences & Humanities (SH1)

HEALIN – Healthy lifespan inequality: Measurement, trends and determinants

Despite its widespread use and popularity, life expectancy (LE) has two shortcomings. First, its definition only takes into consideration mortality levels, thus ignoring the health status of those who remain alive. Second, LE is an average that does not explain how length of life is distributed across the population. These limitations have generated two strands of research (i.e. the study of ‘health expectancies’ (HE) and ‘lifespan inequality’ (LI)) that, so far, have developed independently from each other. The overarching objective of the HEALIN project is to bring together these research avenues into a coherent whole to get a more comprehensive understanding of contemporary population health dynamics. To attain this goal, I put forward the new concept of ‘healthy lifespan inequality’ (HLI), which is designed to investigate the extent to which healthy lifespans are unequally distributed across the population. The HEALIN project will (i) investigate the trends and determinants of HLI, (ii) assess whether the specific ages and causes that drive changes in HLI are the same ones determining the changes in LE, HE and LI indicators, and (iii) investigate how these indicators behave across and within countries and socio-economic groups. In addition, the project aims at making innovative contributions to the measurement of co-morbidity and to our understanding on how the latter can in turn influence the measurement of health expectancy and healthy lifespan inequality. To attain these objectives, the project will develop path-breaking analytical methods inspired in the models applied for the study of inequality and multidimensional poverty. Besides traditional socio-economic and health data sources, the project will complementary draw from the vastly underutilized health registers for the entire population in Catalonia (7.5 million residents). Their huge size and micro-level design allow investigating trends in HLI and co-morbidity with unprecedented detail.

Iñaki Permanyer – Centre d’Estudis Demogràfics (CED) 
CoG2020 – Social Sciences & Humanities (SH3)

The world is awakening to alarming environmental costs and geopolitical consequences of the ongoing Digital and Green revolution, which are replacing our reliance on fossil fuels with the one on critical raw materials (CRMs). Governments are anxiously searching for alternative sources of supply, and the importance of technology leadership in the recovery of CRMs and other valuable elements from secondary sources is evident. ELECTROmonoLITH project will develop a new technology for selective recovery of lithium and other valuable metals (e.g., cobalt, nickel, copper) from complex waste streams and natural/anthropogenic brines such as battery recycling wastewater, e-waste leachate, and geothermal brines. Long-standing challenges of electrochemically switched ion exchange – poor material stability, low recovery rates and capacities, insufficient selectivity, and high energy costs, will be overcome by developing monolith electrodes with mass transfer-enhancing structure, tailored for highly selective capture of specific metals from multi-component solutions using surface-imprinted ion-selective recognition units. Highly ordered electrode architectures with accessible active sites for metal ion cycling will endow the monolith electrodes with high space-time yields, minimize the pressure drop and thus hydraulic energy requirements, and enable the production of large volumes of high purity CRM concentrates in a more energy-efficient way. Given the inherent modularity of electrochemical systems, their scalability, autonomous operation and easy coupling to renewable energy sources, as well as the possibility to integrate electro-extraction of target metals with electrooxidation of organic pollutants, ELECTROmonoLITH project has the potential to provide a platform technology for both resource recovery and wastewater treatment, and to respond to major challenges of the water-energy nexus.

Jelena Radjenović – Institut Català de Recerca de l’Aigua (ICRA)
CoG 2022 – PE8

The goal of this proposal is to build tools to better understand the economic impacts of the rapid transformation of electricity markets, and to help better design electricity markets going forward. I propose to develop and implement novel statistical tools and structural models that contribute to our understanding of this rapid transformation. The proposed research focuses both on firm strategic responses and investment (supply-side), as well as consumer behavior and welfare and distributional impacts (demand-side). The proposal presents several projects and methodologies that examine these issues in detail with unique high-frequency micro-data on firms and households. The tools and models developed in this proposal can help understand the impacts of the energy transition, both on the supply and the demand side. Among the expected methodological contributions, I plan to combine machine learning tools with more standard structural modeling. On the supply side, the proposal emphasizes the need to understand how strategic behavior interacts with market design in the presence of intermittent resources. On the demand side, the proposal highlights the importance of understanding the distributional implications of such changes with special attention to the residential sector and the most vulnerable socio-economic households.

Mar Reguant– Institut d’Anàlisi Econòmica (IAC-CSIC)
CoG 2020 – Social Sciences & Humanitites (SH1 – Individuals, Markets & Organizations)

The growing occurrence of antimicrobial-resistant infections, compounded with the stalling development and approval of new antibiotic drugs, has created a therapeutic gap, threatening a global health crisis. Resistance emerges when bacteria mutate their molecular targets for antibiotics, evading their action. Is it conceivable to design synthetic cells assembled from abiotic synthetic macromolecules, capable of mimicking the most salient features of phagocytosis —Nature’s most selective, effective, and advanced strategy to eradicate pathogens? The aim of PhagoSynCell is to create Phagocytic Synthetic Cells (PSCs) that selectively recognize, capture, engulf and kill antibiotic-resistant bacteria without generating selection pressure for resistance. Firstly, we will develop the membrane of the PSCs by the simulation-aided synthesis of novel macromolecular amphiphiles (Janus dendrimers and amphiphilic comb polymers) self-assembled into vesicle libraries with functional diversity and phenotype programmability. We will then study novel methods to facilitate engulfment of micro-objects by leveraging principles of mechanical actuation programmed at the molecular level. We will introduce superselectivity to artificial membranes to selectively capture bacteria. Furthermore, we will develop an antimicrobial strategy triggered and activated by engulfment that disrupts the bacterial membrane —an element highly unsusceptible to evolution. Finally, we will demonstrate the efficacy of PSCs against pathogenic antibiotic-resistant strains and show their biosafety in cells, organoids, and advanced tissue models as proof-of-concept for future applications. PhagoSynCell will unveil the underlying principles of Artificial Phagocytosis, delivering synthetic cells able to selectively recognize and kill bacteria. Ultimately, this will provide the steppingstone towards the use of synthetic cells as a quasi-living therapeutic —a field I envision will revolutionize medicine.

César Rodriguez-Emmenegger – Institut de Bioenginyeria de Catalunya (IBEC)
CoG 2024 – PE5 – Physical Sciences & Engineering – Synthetic Chemistry & Materials

The concept of diffusion is ubiquitous in the physical sciences. From the mathematical point of view, its study started in the early 19th century with the development of PDE theory, and has many connections to Physics, Probability, Geometry, and Functional Analysis. This project aims to answer several outstanding questions related to the mathematics of diffusion.

The proposal is divided into two blocks. The first one corresponds to the study of stable solutions to reaction-diffusion PDE, and more precisely the classification of global stable solutions in the physical space (i.e., in 3D) for a general class of problems including the Allen-Cahn, the Alt-Phillips, or the thin Alt-Caffarelli equations. We will also investigate the same question for complex-valued solutions in 2D, which arises in the construction of travelling waves for the Gross-Pitaevskii equation. The second block corresponds to nonstandard diffusions. In particular, we will study the Boltzmann equation (a fundamental model in statistical mechanics), nonlocal diffusions (deeply related to Lévy processes and “anomalous diffusions”), as well as the porous medium equation (a classical nonlinear PDE that arises in various physical models in which diffusion is “slow”). The highly ambitious goals of the project are motivated by some recent results obtained by the PI in these areas.

Xavier Ros-Oton – Universitat de Barcelona (UB)
CoG 2022 – PE1

Studying the collective behaviour of enzyme nanobot swarms

Inspired by flocks of birds and schools of fish, researchers in the nanorobotics field are focussing on achieving the same movement complexity and implementing swarm behaviours in artificial systems. So far, artificial nanobots have been explored at an individual level. The study on how nanobots propel themselves, navigate and communicate in biologically relevant environments has received little attention. To study their cooperative behaviour, the EU-funded i-NANOSWARMS project will develop enzyme-powered nanobot swarms capable of self-propelling using biocompatible and bioavailable fuels. The project will be a proof-of-concept of the pertinence of intelligent nanoswarms to biomedical applications, enhanced drug delivery and medical imaging.

Objective of the project:

In nature, systems composed of self-propelling agents display complex behaviors such as signal interpretation, propagation, amplification and engage in collective motion mediated by interactions between different agents and their environment. Examples range from swarming bacteria to schooling fish and flocking birds. These self-organized systems have served as an inspiration for researchers seeking to achieve complexity in artificial systems composed of synthetic agents. A class of agents that has recently been demonstrated is of synthetic nanomachines (nanobots) that can self-propel thanks to the conversion of chemical energy, harvested from the environment, into motion. While most of the artificial nanobots have been explored at individual level, their collective emergent behavior, arising from inter-particle interactions through chemical and hydrodynamic fields, and through environment mediated interactions is yet to be properly studied. Understanding collective effects will be especially useful in biologically relevant environments, where a number of applications for these nanobot systems have been envisioned.

i-NANOSWARMS aims to realize enzyme-powered nanobot swarms capable to self-propel using biocompatible and bioavailable fuels and display collective and cooperative behaviours through communication among them as well as with the host environment. The proposal is divided in three working packages. In WP1, I will create a toolbox of nanobots based on a library of enzymes and nanoparticle architectures to study communication and long-range signal propagation using enzyme cascades. WP2 will be devoted to the collective behavior of nanobot swarms, exploiting biomimetic strategies such as chemotaxis and stigmergy to guide and recruit other nanobots. WP3 aims at studying, as a proof-of-concept of the applicability of intelligent nanoswarms for biomedical applications, cooperative behavior among nanoswarms for enhanced drug delivery and medical imaging.

Samuel Sánchez Ordóñez – Institut de Bioenginyeria de Catalunya (IBEC)
CoG2019 – PE8 -Physical Sciences Engineeering – Products & Processes Engineering

Cell types are the basic constituents of animal multicellularity, with each type defined by a gene regulatory program that specifies cell function and structure. Thus, understanding cell type diversity is key to explaining animal adaptation and evolution. However, despite recent advances in the molecular characterization of cell types, the phylogenetic relationships between animal cell types remain obscuremainly because we do not understand how the different elements of a cell type identity program (e.g. transcription factors and regulatory sequences) change over time and how these changes translate into cellular novelties.

This project will bridge the gap between cell type micro- and macroevolution, focusing on Cnidaria as a model to study cell type evolutionary processes. We will measure and compare cell identity characters across divergent timescales: from intraspecies variation between sea anemone populations, to cross-species comparisons within Cnidaria, to cross-phyla cell phylogenies. By combining single-cell and functional genomics experiments with advanced computational methods, we will: (i) build whole-organism genotypephenotype maps at cellular resolution, to explain the genetic basis of cell type evolution; (ii) model the evolutionary processes underlying the diversification, novelty, and functional adaptation of cell types across the cnidarian phylum; and (iii) study the evolutionary conservation and divergence rates of cell type regulatory characters to resolve the phylogenetic relationships between animal cell types (e.g. neurons, gland, epidermal, and sensory cells).

The expected results will offer a multi-level, quantitative, and phylogenetic perspective on animal cell types, allowing us to test long-standing hypotheses about cell type evolution. Our novel comparative framework will lay the foundations of cell systematics and provide transformative insights into a fundamental question in biology: how do cell types originate and diversify?

Arnau Sebé-Pedrós – Centre de Regulació Genòmica (CRG)
CoG 2024 – Life Sciences (LS8 – Environmental Biology, Ecology & Evolution)

SuperComp – Unconventional Superfluids in Quantum Gases with Competing Interactions

Unconventional superfluids, where frictionless flow appears combined with features such as topological excitations or crystalline order, are some of the most surprising collective quantum phases of matter. Although the corresponding topological superfluids and supersolids were originally predicted in condensed matter, ultracold quantum gases provide a more controlled experimental approach to these phases, and promise microscopic access to their exotic properties. A key mechanism towards unconventional superfluidity is the competition in the same system of interactions of different origins, a situation naturally addressed by multicomponent gases. When these interactions have opposite signs, new and surprising phases emerge. A prime example is the ultradilute quantum liquid phase recently observed by my group in a mixture of Bose-Einstein condensates, which is most likely only the first item in a long list of new unconventional phases. The goal of SuperComp is to exploit the full potential of quantum gases with competing interactions to unlock the observation of unconventional superfluid phases that have until now defied experimental realization. To this end, I will explore three distinct mechanisms resulting in unconventional superfluid behavior: quantum fluctuations, engineered dispersion relations, and interactions with non-zero orbital angular momentum. Exploiting combinations of bosonic and fermionic potassium atoms, I will realize novel types of ultradilute quantum liquids, supersolid-like gases and liquids, density-dependent artificial gauge fields, elastic multi-body interactions, and investigate a new approach towards the long-sought px+ipy topological superfluid phase of 2D Fermi gases. These experiments will deepen our understanding of the mechanisms responsible for unconventional superfluidity, and impact not only the field of quantum gases, but also the much broader range of disciplines where unconventional superfluids or superconductors play a key role.

Leticia Tarruell – Institut de Ciències Fotòniques (ICFO)
CoG2020 – Physical Sciences & Engineering (PE2)

Is the human mind an evolutionary one-off? Or does it reflect a ‘universal mind’ in which similar cognitive mechanisms repeatedly evolve via convergent evolution? Avian cognition offers a powerful model system for answering this fundamental question about the nature of our mind, because birds last shared a common ancestor with humans 312 million years ago and have evolved brains with a very different structure. However, to unlock the potential of this model system we need to robustly test whether mechanistic convergence has occurred between the minds of birds and humans (the convergent mind hypothesis) and rule out cognitive similarities between birds and humans due to shared ancestry (the ancestral mind hypothesis). UNI PROB takes advantage of decades of research on probabilistic inference, a central, but imperfect aspect of human cognition, to overcome these challenges. To test for mechanistic convergence, UNI PROB will use the cognitive biases and errors humans show in their probabilistic inferences (e.g. the conjunction fallacy, base rate neglect and the hot hand fallacy) as diagnostic signatures for the presence of a similar cognitive system in a species demonstrating the best performances on probabilistic inference tasks of any animal tested to date: the kea parrot. To test for shared ancestry, UNI PROB will present novel, non-verbal probabilistic inference problems not only to humans and kea, but also to a phylogenetic control for shared ancestry: rats. If convergent evolution has occurred, then only humans and kea will solve these problems while showing the same cognitive biases and errors. By testing for the convergent evolution of this cognitive system, UNI PROB can generate conclusive evidence that probabilistic biases are adaptive features of the human mind and discover if there is a new frontier in cognitive science, namely a universal mind that evolves repeatedly via convergent evolution.

Alex Taylor – Universitat Autònoma de Barcelona (UAB)
CoG2021 – Social Sciences & Humanities (SH4 – The Human Mind and its Complexity)

CERQUTE – Certification of quantum technologies

Given a quantum system, how can one ensure that it (i) is entangled? (ii) random? (iii) secure? (iv) performs a computation correctly? The concept of quantum certification embraces all these questions and CERQUTE’s main goal is to provide the tools to achieve such certification. The need of a new paradigm for quantum certification has emerged as a consequence of the impressive advances on the control of quantum systems. On the one hand, complex many-body quantum systems are prepared in many labs worldwide. On the other hand, quantum information technologies are making the transition to real applications. Quantum certification is a highly transversal concept that covers a broad range of scenarios –from many-body systems to protocols employing few devices– and questions –from theoretical results and experimental demonstrations to commercial products–.

CERQUTE is organized along three research lines that reflect this broadness and inter-disciplinary character:
(A) many-body quantum systems: the objective is to provide the tools to identify quantum properties of many-body quantum systems;
(B) quantum networks: the objective is to characterize networks in the quantum regime;
(C) quantum cryptographic protocols: the objective is to construct cryptography protocols offering certified security. Crucial to achieve these objectives is the development of radically new methods to deal with quantum systems in an efficient way.

Expected outcomes are:
(i) new methods to detect quantum phenomena in the many-body regime,
(ii) new protocols to benchmark quantum simulators and annealers,
(iii) first methods to characterize quantum causality,
(iv) new protocols exploiting simple network geometries
(v) experimentally-friendly cryptographic protocols offering certified security.

CERQUTE goes at the heart of the fundamental question of what distinguishes quantum from classical physics and will provide the concepts and protocols for the certification of quantum phenomena and technologies..

Antonio Acín – Institut de Ciències Fotòniques (ICFO)
AdG2018 – Physical Sciences & Engineering (PE2)

NovoGenePop – Deciphering de novo gene birth in populations

Genes are fundamental units of life and their origin has fascinated researchers since the beginning of the molecular era. Many of the studies on the formation of new genes in genomes have focused on gene duplication and subsequent divergence of the two gene copies. But, in recent years, we have learnt that genes can also arise de novo from previously non-genic sequences. The discovery of de novo genes has become possible by the sequencing of complete genomes and the comparison of gene sets between closely related species. Here we wish to test a novel hypothesis, we propose that de novo gene formation dynamics in populations results in substantial differences in gene content between individuals. If they exist, these differences would be not be visible by the current methods to study gene variation, which are based on the comparison of the sequences of each individual to a common set of reference genes. To test our hypothesis, we will need to develop novel computational approaches to first obtain an accurate representation of all transcripts and translated open reading frames in each individual, and then integrate the information at the population level. We propose to apply these methods to two very distinct biological systems, a large collection of Saccharomyces cerevisiae world isolates and a human lymphoblastoid cell line (LCL) panel. For this, we will collect and generate RNA (RNA-Seq) and ribosome profiling (Ribo-Seq) sequencing data. In order to identify de novo originated events occurred within populations, as opposed to phylogenetically conserved genes that have been lost in some individuals, we will also generate similar data from a set of closely related species in each of the two systems. Combined with genomics data, we will identify the spectrum of mutations associated with de novo gene birth with an unprecedented level of detail and uncover footprints of adaptation linked to the birth of new genes.

Mar Albà – Institut de Recerca Hospital del Mar
AdG2021 – LS8 – Environmental Biology, Ecology & Evolution

A closer look at the Catholic Church’s environmental history

Fifty years ago, historian Lynn White Jr. criticised the Judeo-Christian tradition for exploiting nature. Recently, Pope Francis released an environmental manifesto, advocating against climate change. Has the Catholic Church embraced environmentalism? What challenges has it faced? The ERC-funded CATCH project will document the environmental history of the Catholic Church from the 1960s to the 2000s, highlighting its global influence on environmental issues. The project will explore how the Church has shaped environmental visions and politics. It will explore the Church’s role in environmental governance at international conferences and UN debates, as well as regional case studies in the Americas, Europe, Asia, and Africa. It will produce multiple academic publications and a documentary.

Objective of the project:

Fifty-six years ago, historian Lynn White Jr. published his “J’accuse” against the Judeo-Christian tradition, blaming it for fostering a culture that exploited nature. Half a century later, Pope Francis published an environmental manifesto, positioning himself as a champion against climate change. Has the Catholic Church (CC) embraced environmentalism? What have been its key environmental interventions, turning points, and internal and external frictions?
CATCH will provide the first comprehensive environmental history of the CC from the 1960s—when Vatican II intertwined with the hopes of the 1960s—to the 2000s, with the election of Bergoglio. Scholars have explored the intersection of religion and the environment from theological and philosophical perspectives, leaving historical relationships unexamined. This oversight is significant given the CC’s global influence, including its participation in major environmental conferences and its potential impact on 1.5 billion people. In what ways has the CC shaped environmental visions, politics, and realities?
CATCH aims to address this gap by researching the Church’s environmental engagement across multiple scales. Globally, it will examine its role in environmental governance at international conferences and UN debates. Regionally, it will analyze the CC’s diverse experiences of engagement with environmental issues through case studies in South and North America, Europe, Asia, and Africa.
The PI, with a strong background in environmental history and political ecology, will lead this groundbreaking research. The team will include 5 PhD students, 1 postdoc, and 1 research assistant, supported by 4 senior researchers—each an expert in one of the case studies—and an ethical advisory board with two leading theologians. The project will produce 5 PhD dissertations, a monograph, an edited volume, a special issue, 13 peer-reviewed articles, an open-access oral history repository, and a documentary.

Marco Armiero – Universitat Autònoma de Barcelona (UAB)
AdG2024 – SH6 – Social sciences & humanities – The Study of the Human Past

ALiEN – Autonomous Linguistic Emergence in neural Networks

Deep neural networks (DNNs) are specialized computational models lacking a standard interface. If a complex task requires different DNNs, an ad-hoc connection must be laboriously designed. Inspired by human language, ALiEN wants to replace such ad-hoc interfaces with generic communication protocols optimized for ease of learning by DNNs that might have different architectures and functions. ALiEN “languages” are not hand-crafted: they emerge by training DNNs to share information through communication, offering the scalability and robustness to noise that is an asset of learned systems. A first set of experiments will study, in tightly controlled settings, the impact of input, training community size and communication channel on the expressiveness and ease of acquisition of emergent protocols. The emergence of general protocols will be encouraged by a training environment characterized by varied inputs and interaction among numerous DNNs. The best emerged protocols will also be taught in a supervised way to new DNNs, with the final aim of establishing a “universal” DNN language. Next, I will explore how emergent protocols can help interfacing out-of-the box, state-of-the-art DNNs, only requiring the addition of light input and output layers to existing pre-trained models. Finally, a simplified home automation use case will demonstrate the usefulness of emergent protocols in a scenario that features some of the complexities to be expected in real-life applications. The project will also thoroughly analyze the emerging protocols, with the concurrent aims of i) identifying and favoring features that make them more expressive and easier to learn; ii) enhancing interpretability; and iii) gathering scientific insights into communication emergence in a non-human “species”. All in all, ALiEN will take a first bold step towards enabling autonomous DNN interaction, and thus genuinely adaptive AI systems.

Marco Baroni – Universitat Pompeu Fabra
AdG 2020 – PE6

residualCRC – Mechanisms Behind Residual Disease in Colorectal Cancer and Modellinf of Therapies that Prevent Relapse

Disease relapse is a major complication in colorectal cancer (CRC). At the time of diagnosis, the majority of patients will present with locoregional disease that can be effectively resected by surgery. This intervention is sufficient to cure the primary disease in most cases. Yet, over the course of the following months or years, around 40% of the patients that underwent resection of the primary tumor with curative intention will relapse, generally in the form of metastatic disease. As these metastases eventually interfere with the function of vital organs such as the liver and lungs, patients that undergo relapse have poor prognosis. Recurrent cancer arises from clinically occult tumor cells that have disseminated to foreign organs (disseminated tumor cells or DTCs) before surgical removal of the primary CRC. Although the time window between surgery and relapse offers a good opportunity to prevent metastasis, current therapies are not effective at eliminating DTCs. Thus, there is an important unmet need to develop strategies to target residual disease. Advances in this area will benefit a large proportion of patients. Despite its clinical relevance, the study of residual disease in CRC has been largely neglected and the principles that govern the behavior of DTCs remain unknown. The main reason for this important knowledge gap is that residual tumor cells are difficult to study in patients, as they remain clinically occult. We have recently generated a unique set of compound mutant mice and organoids that reproduce key features of human metastatic CRC. We propose to leverage these new models to study the biology of residual disease. We will characterize the features of DTCs using single cell transcriptional profiling, analyze the influence of driver mutations on DTC behavior, explore mechanisms of immune evasion during the latency phase, and model DTC latency in vivo and in vitro. Our ultimate goal is to design therapies that prevent disease relapse in CRC.

Eduard Batlle – Institut de Recerca Biomèdica (IRB Barcelona)
AdG 2019 – LS4

CONDJUST – Conservation Data Justice

CONDJUST will create a new research field, Conservation Data Justice, that bridges three distinct areas of enquiry: conservation prioritisation, political ecology and Data Justice. The former uses data which risk marginalising rural peoples. The latter does not yet examine conservation data. Meanwhile political ecologists do not yet consider Data Justice approaches when tackling conservation prioritisation. CONDJUST will interrogate conservation data and models, and explore the epistemic communities producing them, to develop new theories of socially just, data-driven conservation. It will challenge the colonising tendencies of prioritisation work and seek decolonising alternatives.

CONDJUST is timely because ambitious new global targets seek to safeguard 30% of the planet for conservation by 2030 (and more afterwards). These plans pose risks for rural people because the data and modelling they use can contain diverse forms of bias, exclusion and omission. These risks will grow as more social media data are used in conservation prioritisation. We need insights from Data Justice to understand these dangers, and how they might be counter-acted.

This project has four objectives, each with a corresponding work package. These are:

1. Systematically examine the sources of bias and distortion in conservation data used in global prioritisation work.
2. Use Data Justice thinking in new analyses of biodiversity conservation, and increase our understanding of socially just conservation prioritisation.
3. Critically explore the construction of different epistemic communities in conservation prioritisation, and political ecology, to understand what inhibits and enhances learning between them.
4. Examine how policies responding to prioritisation are shaped by, or resist, the new measures proposed.

These work packages will be pursued by an interdisciplinary team led by the PI and composed of three post-doctoral researchers, two PhDs, an administrator and an advisory board.

Dan Brockington – Universitat Autònoma de Barcelona (UAB)
AdG2021 – SH7 – Human Mobility, Environment & Space

ARTSOUNDSCAPES – The sound of special places: exploring rock art soundscapes and the sacred

The ARTSOUNDSCAPES project deals with sound, rock art and sacred landscapes among past hunter-gatherers and early agricultural societies around the world. The potential of sound to stimulate powerful emotions makes it a common medium for conferring places with extraordinary agency. Ethnographic and ethnohistorical sources indicate that these sites are often endowed with a sacred significance and, in many cases, they also receive special treatment, including the production of rock paintings. Despite the aural experience being an integral component of the human condition and a key element in ritual, archaeology has largely been unable to study it systematically. Rock art landscapes are no exception and, although some studies have been made, they have largely been reproached for their lack of scientific rigour and subjectivity. ARTSOUNDSCAPES will fully address this weakness by investigating the perception of sound in rock art landscapes from an interdisciplinary approach. Borrowing methods developed in acoustic engineering, the project will assess, from an objective and quantitative perspective, the acoustic properties of rock art landscapes in selected areas around the world: the Western/Central Mediterranean in Europe, Siberia in Asia, Namibia in Africa and the Sonoran Desert in North America.

Human experiences associated with altered or mystical states invoked by the identified special sonic characteristics of these landscapes will be further tested by exploring the psychoacoustic effects these soundscapes have on people and their neural correlate to brain activity. The project will also thoroughly survey ethnographic attitudes to sacred soundscapes based on both current premodern societies and ethnohistorical sources. The groundbreaking combination of this array of interdisciplinary approaches will facilitate the ultimate aim of the project: to propose a phenomenological understanding of sacred soundscapes among late hunter-gatherers and early agriculturalists around the world.

Facebook: www.facebook.com/artsoundscapes

Web page: www.archaeoacoustics.ub.edu

Margarita Díaz-Andreu – Universitat de Barcelona (UB)
AdG2017 – Social Sciences & Humanities (SH6)

MARKET POWER – Labor Market Risk and Skill Diversity: Implications for Efficiency, Policy, and Estimation

In the last four decades, there have been a number of significant secular trends in the advanced economies around the world. Wage inequality has risen sharply, and most of the wage gains have been appropriated by the top 1%. In addition, labor market dynamism and new startups have declined, the labor share of total output has fallen, low skilled wages have stagnated, and there has been reallocation of production from small to superstar firms. During the same four decades, there has also been a sharp secular increase in market power. Firms set higher prices, profit rates are higher, and scale economies are up. In this proposal, I address the question whether these secular trends are related. Specifically, I ask whether the rise of market power has caused these profound macroeconomic changes. The objective is to uncover economic mechanisms that help understand this fundamental transformation and the implications for efficiency and welfare. I propose to investigate both the causes of the rise in market power and its macroeconomic consequences. I distinguish between causes that stem inherently from the market structure (such as antitrust enforcement and Mergers & Acquisitions) and those that result from technological change (economies of scale, intangible assets, and network externalities). Methodologically, this research proposal aims to contribute to the literature on three fronts: 1. the measurement of markups, 2. to derive theoretical results linking market power and macroeconomic consequences, 3. to estimate and quantitatively evaluate these models. The close link between the macroeconomic consequences and the causes of market power renders this a research proposal at the intersection of macro/labor, industrial organization and law & economics. The objective is to inform the policy debate: how to keep market power under control in order to remediate its macroeconomic consequences that were hitherto considered independent.

Jan Eeckhout – Universitat Pompeu Fabra (UPF)
AdG 2019 – Social Sciences & Humanities (SH1)

When market power tilts the balance and shapes inequality

In advanced economies, a handful of firms have captured an ever-growing share of profits, while workers’ share of income declines. This is what economists call ‘market power’. It is the ability of large firms to set prices, wages, and the rules of the game. The ERC-funded MACRO_POWR_DISTRBUTN project aims to explain how this power shapes inequality. Using data from Belgium and the USA, the project will study firm size, financial constraints, and automation to determine how these factors influence wages, profits, and investment. The project’s goal is to explain why some companies enjoy higher profits but pay proportionally less to labour and how smarter policies could restore balance between efficiency and fairness.

Objective of the project:

Market power is about the distribution of economic surplus between firms, customers and workers. In this proposal, I use modern heterogeneous agents macro tools that incorporate heterogeneity in firm productivity, in preferences, and in market structure. I investigate the macroeconomic mechanisms that link market power and distributional characteristics and formulate welfare-improving policies that lead to efficiency gains and re-distribution.

I propose a unifying framework of market power and distribution in general equilibrium, and use unique data to address the following 3 questions:

1. How does firm size determine monopsony power? Large firms have lower markups yet higher markdowns. This is a key determinant behind the lower labor share in superstar firms, but we have no mechanism that explains why. I propose to use the unifying framework and Belgian VAT transaction data combined with matched employer-employee data to quantify the economic mechanism by which markdowns vary in the firm size distribution.

2. How do financial frictions influence market power? Low productivity firms tend to face tighter financial constraints, leading to higher dispersion in the distribution of capital and technology. This in turn increases market power. I have access to data from a private bank (Caixabank) on a representative sample of firms’ payroll, accounts, as well as credit. Within the unifying framework I aim to quantify the impact of financial frictions on the distribution of market power.

3. How does labor-saving technological change affect the distribution of the labor share and market power? Technology adoption is driven by the firm’s attempt to increase profitability. Incorporating general equilibrium effects and market power, I propose to analyze the substitution patterns within and between firms with the introduction of new technologies. I will use US Census data to quantify the distributional effects of labor-saving technological change.

Jan Eeckhout – Universitat Pompeu Fabra (UPF)
AdG2024 – SH1 – Social sciences & humanities – Individuals, Markets & Organisations

Ultrafast electron microscopy relies on the spatial, spectral, and temporal manipulation of free electrons with nm/meV/fs precision to map the structural dynamics as well as the vibrational and electronic ground and excited states of nanomaterials. With QUEFES I will introduce a conceptually disruptive approach to capitalize on the quantum nature of free electrons and their interactions with matter and radiation fields aiming to obtain previously inaccessible information on the atomic-scale dynamics of such materials, to reveal hidden properties of the quantum vacuum, and to control the many-body state of quantum matter.
I will address five challenges of major scientific relevance: (i) the spatiotemporal control over the density matrix of free electrons by interaction with suitably designed optical fields to overcome the current limits of space/time/energy resolution in time-resolved electron spectromicroscopy; (ii) a disruptive approach to map the nanoscale quantum fluctuations and the out-of-equilibrium state associated with optical near fields in vacuum and polaritonic excitations in nanomaterials; (iii) a Fourier-transform-inspired method to image the spatiotemporal evolution of atomic structures, charge carriers, and dynamical screening; (iv) the use of free electrons to flexibly read and write the many-body quantum state of trapped Rydberg atoms and quantum gases; and (v) the realization of all-electron pump-probe spectroscopy combined with the formation of dynamically screened multiple free-electron bound states for lossless charge transport in a semiconductor.
I will pursue these research frontiers by relying on the strong interdisciplinary theoretical background of my group at the intersection between electron-light-matter interactions and nanophotonics, introducing a change of paradigm in the use of free electrons to break the current limits of spectromicroscopy and having the potential for revolutionizing our ability to image and manipulate the nanoworld.

F. Javier García de Abajo – Institut de Ciències Fotòniques (ICFO)
AdG2023-  Physical & Engineering Sciences (PE3) – Condensed Matter Physics)

Processions were quintessentially performative acts that infused a sense of identity among the urban community by linking the emblematic topography of the city and creating performative spaces of enhanced ritual activity and distinctive auditory landscapes. The premise of Soundspace is that hermeneutic study of the procession as performance affords insight into the dynamic workings of society and the experience of urban life. It aims to go beyond this to assess the impact of urban ritual on participants and ear-witnesses through analysis of the social and cultural processes that lay behind that experience, and of the perceptual discourses that gave it meaning and significance for all those present. The procession formed a moving intersensory experience that also mobilised the emotions of the urban community: but how did this work in practice in the historical past? How can the historian enter into the performative moment to understand the emotional impact of sound in acoustic space? The project aims to interrogate the multi-faceted relationship between sound, space and society by scrutinising the interstices between collective experience, social expectations and memory through the prism of historical sound studies, an umbrella term here used to combine a cross-disciplinary approachurban studies, sensory history and history of the emotionsand DH tools: Virtual Reality, digital cartography and semantic discourse analysis. It will forge a new theoretical framework by combining concepts of acoustic and emotional communities to analyse the social and cultural processes involved in the preparation, performance, reception and impact of the procession and the prevailing discourses that forged the significance of processional expression for the urban community. The main objective is to open up new ways to explore the impact of intangible but key features of processions such as acoustic space, soundscape competence, density of sensory experience and emotional response.

Tess Knighton – Universitat Autònoma de Barcelona (UAB)
AdG2023-  Social Sciences & Humanities (SH5 – Cultures & Cultural Production)

NOVOFLAT – Escaping from Flatland by “de novo” Catalytic Decarboxylation Techniques

Although cross-coupling reactions have become one of the pillars of modern chemical synthesis, the ability to forge sp3–sp3 bonds with improved flexibility, practicality, predictable site-selectivity, preparative utility, stereocontrol and with nearly zero-generation of waste has eluded chemists for decades, remaining a major challenge and an uncharted cartography in catalytic endeavours. The successful realization of this goal will represent a paradigm shift from the standard logic of organic synthesis in both basic and applied research, as increasing the number of sp3-hybridized carbon atoms has become a necessary goal in the drug discovery pipeline. NOVOFLAT offers a pioneering approach for forging sp3–sp3 linkages via a triple catalytic cascade that enables an unprecedented intramolecular decarboxylation of simple and available carboxylic acid esters with CO2 as the sole byproduct. As ester derivatives simply derive from naturally-occurring carboxylic acids and alcohols, this proposal will allow to rapidly access sp3–sp3 linkages with different electronic and steric requirements, thus providing an invaluable opportunity to streamline the discovery of important architectures with applications across the molecular sciences. Preliminary results demonstrate the feasibility to provide “a la carte” predictable tool that chemists could use to control the site where the sp3–sp3 bond-formation takes place in both aliphatic and cyclic frameworks, even at remote sp3 sites. In addition, our general principle offers an unrecognized opportunity to simultaneously construct sp3–sp3 linkages and control the stereochemistry at remote sp3 sites. In this manner, NOVOFLAT will not only provide new dogmas in retrosynthetic analysis by fundamentally altering the way sp3–sp3 bonds are made, but also open new vistas in “chain-walking” reactions, as the incorporation of chirality throughout the alkyl side-chain constitutes “terra incognita” in these technologies.

Ruben Martin – Institut Català d’Investigació Química (ICIQ)
AdG 2019 – Physical Sciences & Engineering (PE5)

MiniEmbryoBlueprint – The mammalian body plan blueprint, an in vitro approach

The development of an embryo requires the spatially structured emergence of tissues and organs. This process relies on the early establishment of a coordinate system in the form of three orthogonal axes that act as a reference for laying down the body plan, a template for the organism. Genetic analysis of this process has revealed an underlying transcriptional blueprint that links the coordinate system and the body plan. However, the way in which the gene products contribute to the emergence of the body plan remains an open question. A reason for this is that this process involves feedbacks and integration between the activity of Gene Regulatory Networks (GRNs) and the mechanics of multicellular ensembles, and that probing this relationship is experimentally challenging. In the case of mammalian embryos, which are particularly important as models for human development, our gaps in knowledge of these events are larger than in other organisms. This is partly due to the challenges associated with uterine development but also, and increasingly, because of the cost of mice and the difficulty of obtaining large numbers of embryos, as required for mechanistic experiments. In this project we shall use gastruloids, a novel and versatile Pluripotent Stem Cells based experimental system that we have developed for the study of mammalian development, to gain insights into the molecular and cellular basis underlying the emergence of the mammalian body plan. Gastruloids lack anterior neural structures and over a period of five days become organized in the fashion of a midgestation mouse embryo. We shall use the experimental versatility of the Gastruloid system to probe into the functional relationships between the mechanical activities of multicellular ensembles and the dynamics of GRNs that underlie the emergence of the mammalian body plan.

Alfonso Martínez Arias – Universitat Pompeu Fafra (UPF)
AdG2018 – Life Sciences (SL3)

CLIPOFF-CHEM – Clip-off Chemistry: Design and Synthesis of New Materials via Programmable Disassembly of Reticular Materials

Historically, innovations in synthetic methods and reactions have changed the way scientists think about designing and synthesizing materials and molecules. Indeed, novel synthetic methods not only unlock access to previously unattainable structures, but also inspire new concepts as to how we design and build materials to address global social, economic and industrial needs. The project that I propose here, CLIPOFF-CHEM, centers on the demonstration of a novel synthetic methodology that I have named Clip-off Chemistry. Unlike most state-of-the-art synthetic approaches, which use bottom-up strategies to link atoms and molecules through the formation of new bonds, Clip-off Chemistry is based instead on the selective cleavage of existing bonds in reticular materials, providing precise spatial control over bond cleavage. In reticular materials, this cleavage can be programmed to enable the synthesis of limitless materials varying by composition (from organic to metal-organic), dimensionality (from 3-D to 0-D) and size-scale (from macro- to nanoscale). Accordingly, in CLIPOFF-CHEM, I will employ clip-off synthesis to prepare a diverse collection of new materials and molecules, including new 3-D metal-organic frameworks (MOFs), low-dimensional (2-D and 1-D) materials, organic polymers, metal-organic polyhedra (MOPs), complexes and macrocycles. Our work will encompass 1) synthesis of the reticular material precursors (MOFs, COFs and MOPs) that incorporate non-cleavable and cleavable (alkene/alkyne) groups in precise positions of their structures; and 2) cleavage of alkene/alkyne groups through ozonolysis to produce the targeted materials. As the resultant products will be novel, we will also endeavor to identify and characterize any unprecedented structural or functional properties of them. I believe that CLIPOFF-CHEM will provide the global scientific community with an innovative methodology for the design and synthesis of new functional molecules and materials.

Daniel Maspoch – Institut Català de Nanociència i Nanotecnologia
AdG 2020 – PE5

Understanding the physics behind gravitational waves

Gravitational waves, first detected in 2015, have opened a new window into the universe. Future detectors like the Einstein Telescope and space-based missions such as LISA promise to discover many more, from events as far back as the early universe. However, understanding the physics behind these waves is a huge challenge, especially when quantum matter interacts with gravity. Traditional approaches struggle with these complex, out-of-equilibrium conditions. In this context, the ERC-funded HoloGW project aims to tackle this by using holography, a powerful theoretical tool, to study phenomena like neutron star mergers, phase transitions, and spacetime singularities. This work will help bridge the gap between theory and the upcoming wave of gravitational discoveries.

Objective of the project:

The revolution unleashed by the discovery of gravitational waves will gradually unfold over the coming decades. The detection of a neutron star merger by LIGO and Virgo opened a new era in multi-messenger astronomy. Future ground-based interferometers, such as the Cosmic Explorer and the Einstein Telescope, will extend the range of detection to the entire Universe, and the frequency to millions of detections per year. Space-based missions like LISA may discover gravitational waves from phase transitions in the early Universe.

Reaping the benefits of this experimental revolution requires a theoretical understanding of quantum matter coupled to dynamical classical gravity. The fact that the relevant physics is often out-of-equilibrium and/or strongly coupled makes this a challenging regime for conventional approaches. The purpose of this project is to use holography, also known as gauge/string duality, to make essential contributions in this direction. I have recently pioneered and provided proof of concept that this line of research is both powerful and feasible. In the next five years I will turn these initial investigations into a fully-fledged research program to improve our understanding of: (i) Cosmological phase transitions, in particular of bubble dynamics and baryogenesis; (ii) Neutron stars, with a focus on out-of-equilibrium physics in binary mergers; (iii) Spacetime singularities, specifically in the presence of quantum matter effects.

These three main objectives are interconnected by two horizontal lines: (i) Identification of universal observables, which hold the best potential to make contact with experiment; (ii) Communication with other fields, which is crucial for the success of an interdisciplinary proposal.

David Mateos – Universitat de Barcelona (UB)
AdG2023 – PE2 – Physical Sciences & Engineering – Fundamental Constituents of Matter

The formation and properties of exoplanetary systems is a fascinating question, which has been at the heart of our quest to define mankind and the conditions for life to develop in a broader context.

Recent astronomical observations have deeply modified our paradigm of planet formation, as they suggest the so-called “”proto-planetary disks surrounding T-Tauri stars may actually already host planets. Moreover, we have obtained some of the first observational clues that the dust particles contained in the pristine disk-forming reservoirs that are the embedded protostars may already have significantly evolved from the submicronic dust populating the interstellar medium. These results suggest that dust evolves significantly
already during the first 0.5 Myrs of the star formation process, and highlight the prime importance of understanding the properties and evolution of dust in young protostars.

The PEBBLES project aims at developing a thorough methodology to characterize the properties of dust in embedded protostars, where we know the star and its disk are forming concomitantly. Using an innovative methodology combining cutting edge observational datasets, dust models and numerical models, we aim to transform our understanding of:
1) The nature of the dust incorporated in the youngest disks, a key for models of disk evolution towards planetary systems
2) The processes at work for dust evolution in young protostars, from envelopes to disk scales
3) The efficiency of magnetic fields to couple to the star/disk forming material, and set the disk properties

By shedding light on early dust evolution, we will not only address one of the oldest and most challenging question regarding the initial conditions for planet formation in disks around solar-type stars, but also provide new insight to the conditions reigning and their impact on physical processes during the main accretion stage, during which stars acquire most of their properties.

Anaëlle Maury – Institut de Ciències de l’Espai (ICE – CSIC)
AdG 2022 –  Physical Sciences & Engineering (PE9 – Universe Sciences)

Field-SEER will develop magnetic sensors with combined spatial, temporal, and field resolution beyond what is possible with existing sensing approaches. The “energy resolution” of a sensor describes this combined performance, and determines a sensor’s ability to detect weak, localized and transient signals. In today’s best-developed sensors, the energy resolution is known to be limited by a combination of intrinsic quantum noise and self-interaction effects. Field-SEER will develop sensors that evade such limits, and in doing so establish a new paradigm for extreme field sensing. The immediate fruits of this new approach will be sensors for two exceptionally demanding contemporary applications: First, a spinor Bose-Einstein condensate co-magnetometer will be developed to search for short-range forces predicted by several models of physics beyond the standard model. Second, optically-addressed nuclear spin ensembles will be developed as high-density vapor-phase magnetometers for next-generation magnetic brain imaging. In both cases, orders-of-magnitude improvement are predicted both for the energy resolution and for application-specific metrics. Field-SEER will also study how spin squeezing, predicted to play an important role in these sensors due to their extraordinary coherence properties, can be harnessed for optimal sensing in this new regime of exceptional energy resolution.

Morgan W. Mitchell – Institut de Ciències Fotòniques (ICFO)
AdG 2022 – PE2

How daily life shaped colonial legacies

The early Modern Era was a crucible for globalisation, driven by the translocation of people, goods, and ideas. Yet, the interplay between material culture, daily life, and gender in this period remains underexplored. In this context, the ERC-funded MaGMa project aims to bridge this gap by examining how gendered ideologies and maintenance activities, such as caregiving and food processing, shaped and resisted colonial globalisation from the 16th to the 18th centuries. By integrating archaeology, history, anthropology, and gender studies, MaGMa will scrutinise cultural shifts in the Mariana Islands, uncovering hidden aspects of how daily practices influenced and resisted the emergence of new colonial norms. This pioneering approach promises a comprehensive understanding of early modern global transformations.

Objective of the project:

The proposed project will be the first to investigate the intimate connection between material culture, quotidian life, and gender in the making of and resistance to early modern colonial globalization. The 16th, 17th, and 18th centuries witnessed the rise of historical processes vital to moulding the world to its present shape. While scholars have extensively studied the worldwide translocations of people, goods and ideas, the fact that this globalization also took shape through the cross-continental circulation of engendered ideologies, policies, knowledge, material culture, technologies and skills has not been sufficiently explored; equally under-investigated has been how this same constellation worked in resisting globalization. Through a synergistic transdisciplinary approach, MaGMa will fully address these weaknesses by examining the material worlds constructed at the crossroads of Modern Colonialism, Gender Systems, and Maintenance Activities. The latter is a concept born in Spanish archaeology to highlight the foregrounding nature of a set of structural everyday practices (e.g. care-giving, food-processing, weaving, hygiene and health, the socialization and rearing of children, and the arrangement of living spaces) essential to social continuity and community wellbeing.

Bringing into focused dialogue prehistoric and historical archaeology; history; anthropology, geography; and postcolonial, anticolonial, decolonial, and gender studies, and binding archaeological science, archaeological fieldwork, and archival research, MaGMa will analyse cultural changes and continuities in the Mariana Islands revealing otherwise undetected cultural features. The ground-breaking combination of this array of disciplines and methods will facilitate the ultimate goal of the project: a sound and holistic understanding of how maintenance activities and gender transformations became structural in configuring early modern colonial “new normalities” across the globe.

Sandra Montón Subías – Universitat Pompeu Fabra (UPF)
AdG2023 – SH6 – Social Sciences & Humanities – The Study of the Human Past

Excited aims to advance fundamental understanding to light-initiated reactions in molecular sensitizers that can display quantumcoherent behaviour in their excited state dynamics at room temperature. Moreover, it will focus also on the investigation of quantum coherent contributions to the solar-to-energy conversion efficiency in solar cells.
Understanding the importance of quantum-coherent dynamics in biological systems has been key to assess whether this phenomenon is not just present but key for the control, and command, of the energy transport in molecular based systems. It is of utmost importance to validate models in which these quantum phenomena can be translated to materials that provide efficient solar to power conversion technologies.
Excited is not only a project where molecular solar cells will be fabricated and their physical properties will be measured. Excited goes well beyond that, and will pave the way for the development of solar cells that will be tailor-made to make use of quantum coherence, molecular hybridization and orbital coupling effects to increase the solar to energy conversion efficiency. It is clear that this challenge can only be successful under the scope of a multidisciplinary perspective open to new and feasible reasonable hypothesis. Therefore, I will make use of the research group knowledge on synthetic chemistry that has allowed us to obtain numerous sensitizers for solar cells applications, as well as, for semiconductor metal oxides. Moreover, I will take advantage of our experience in advanced experimental time-resolved techniques to study quantum coherent effects and solar cells under operando conditions. Excited will have a key impact on several fields, from biology to chemistry and physics and will bring paramount breakthroughs in the use of modified interfaces leading to the optimization of novel thin film solar cell technologies taking advantage of the quantum coherence phenomena and orbital coupling effects.

Emilio Palomares – Institut Català d’Investigació Química (ICIQ)
AdG 2022 – PE8

My research project proposes studying the origin of state capacity, democracy and political dynasties using the colonial conquest of Latin America as a natural experiment. Much of the recent work on comparative politics and development uses large historical events as fruitful experimentation laboratories. However, the colonial experience looks more similar to a “”bundle treatment”” than a single treatment. It is difficult to disentangle the role of differences in legal origin from the influences of human capital, etc. To try to overcome this problem, past empirical approaches use a variety of methods like case studies, panel data, country-fixed effects, and instrumental variables. I will try to move one step further in this debate by considering the initial years of the Spanish colonization of Latin America as a natural experiment.
My methodological approach has four advantages. First, since I only analyse the initial years of colonization, my empirical strategy is based on the fact that the initial conquerors had no knowledge of the land that they intended to conquer. The second advantage is that, in working with the colonization of Latin America, we only have one colonial power, Spain, which avoids the traditional problems of diversity of legal origins. The third advantage is that the contracts (Capitulaciones), that the conquerors signed with the King before embarking to America, and before even knowing anything about the land that he would conquer, and other documents from the Archivo de Indias, provide very rich details on the rules that governed the early institutions (power to tax and rule, the use of military power, the treatment of indigenous groups, etc.). Finally, these documents contain information to locate the initial settlements at the subnational level. The colonization of the Americas and the information contained in the Capitulaciones found in the Archivo de Indias provides a unique opportunity to advance the debate on these crucial questions.

Marta Reynal-Querol – Universitat Pompeu Fabra (UPF)
AdG 2021 – Social Sciences & Humanities (SH1 – Individuals, Markets & Organizations)

How animals emerged from their unicellular ancestors remains a major evolutionary question. Work done on diverse unicellular relatives of animals demonstrated that the unicellular ancestor of animals had a larger repertoire of genes associated with multicellularity than previously thought. These include “animal-specific” genes such as protein tyrosine kinases, integrins and Brachyury. This suggests a latent genetic potential in place at the origin of animals and hints at a much more gradual transition in their emergence. However, a comparison of extant early-branching animals and their unicellular relatives still reveals an abrupt difference between protists and the body plans of extant animals. This gap could be due to intermediate lineages going extinct, or that descendants of key lineages have not been found yet. Recent DNA environmental surveys suggest the latter, revealing several novel kingdom-level lineages that branch close to animals and remain unknown.

We will not make progress in understanding the origin of animals until we have explored the real diversity of animals’ closest relatives and isolated the major lineages that remain uncharacterized. Indeed, some of the answers to animal origins that we can not currently address with our taxon sampling are likely hiding in hindsight in those unsampled lineages. Notably, a targeted survey of animal relatives has not been done. I propose to do this by exploiting recent developments in long-read metabarcoding. We will screen different environments and isolate the novel lineages using fixation-free labeling methods. We will culture them and get their genomes.

We will provide a complete picture of the diversity among animal relatives, which will also be relevant to ecologists. Notably, the novel lineages will allow us to address fundamental questions about the origin of animals that cannot be answered with the current taxon sampling, including the origin of embryogenesis and spatial cell differentiation.

Iñaki Ruiz-Trillo – Institut de Biologia Evolutiva (IBE-CSIC)
AdG 2022 – LS8

Emulating viscoelasticity could reveal mechanisms of stem cell differentiation

Many diverse signals modulate the fate and function of cells in living organisms. Mechanical stimuli arising from the surrounding extracellular matrix and neighbouring cells are among these. Most research studying the effects of the mechanical properties of substrates on mesenchymal stem cell (MSC) differentiation has used purely elastic materials. Tissues are viscoelastic and respond in a time-dependent way to force. Thus, viscoelasticity may play a critical role in the differentiation of MSCs and hence in the design of regenerative biomaterials. The ERC-funded devise project will test this hypothesis via a new family of cell-laden viscoelastic hydrogels, using Brillouin microscopy to follow the temporal evolution of their local viscoelastic properties.

Objective of the project:

Tissues are viscoelastic materials whose mechanical properties evolve with time and yet this important property has not been incorporated in the design of regenerative biomaterials. Mechanical properties of biomaterials are known to influence fundamental cellular process, including cell migration, cell growth and cell differentiation. However, most of the work to understand the mechanical properties of substrates on mesenchymal stem cell (MSC) differentiation has made use of pure elastic materials. Cells probe their environment by pulling forces and receiving mechanical feedback through membrane receptors. Since viscoelastic materials respond with a time dependent process to force, we hypothesise that viscoelasticity will play a fundamental role in the differentiation of mesenchymal stem cells and hence in the design of regenerative biomaterials. This project will develop (a) a new family of viscoelastic hydrogels with controlled properties that include biochemical functionalities (recapitulating the properties of the extracellular matrix in vivo), extreme mechanical properties (i.e. very low/high elastic and viscous properties) and mechanical gradients; and (b) Brillouin microscopy to follow the evolution of the local viscoelastic properties of these cell-laden materials as a function of time. we will use viscoelastic materials to promote bone regeneration in vivo using our critical-sized defect in the mouse radius model and, in a major attempt to move the field forward, we will further develop Brillouin microscopy to monitor the viscoelastic properties of regenerative microenvironments in vivo.

Manuel Salmerón – Institut de Bioenginyeria de Catalunya (IBEC)
AdG2021 – PE11 – Physical sciences & engineering – Materials Engineering

Lung diseases are a leading cause of mortality worldwide. Dysregulation of immunomodulatory molecules plays a key role in many pulmonary diseases, including lung cancer, idiopathic pulmonary fibrosis (IPF) and infections. In IPF acute or chronic inflammation results in senescence of the alveolar cells with telomere shortening and/or dysregulation of miRNAs. Modulating the immune response directly or its downstream repercussions could be a possible way to help treat lung diseases. Systemic treatment with immunomodulatory molecules however, can have several drawbacks and include toxic side effects in other organs, the need for continuous delivery and a high cost of production. Similarly, treating immunomodulatory repercussions such as telomere shortening or abnormal miRNA expression in target cells is not easy due to the lack of a technology that efficiently and specifically delivers RNA. Furthermore, viral transformation can result in toxicity and is associated with high costs. To circumvent these problems, we aim to engineer the genome-reduced lung bacterium Mycoplasma pneumoniae as a vector to locally express immunomodulatory proteins, and/or to deliver protein¬–RNA complexes into alveolar cells (Mycovector). M. pneumoniae does not have a cell wall, it directly releases secreted biomolecules into the medium, it does not recombine, it has a unique genetic code that prevents the transfer of genes to other bacteria and we have a non-pathogenic engineered version of it. To design this Mycovector, we will combine our experience in this organism with our know-how in protein design (http://foldxsuite.crg.eu/). We will use our Mycovector expressing different combinations of active biomolecules to treat bleomycin-induced IPF in mice. This project will not only offer new insights into the treatment of a currently incurable disease, but also show that bacterial chassis can be used in other organs different from the gut paving the way to other applications in human health.

Luis Serrano – Centre de Regulació Genòmica (CRG)
AdG 2021 – Life Sciences (LS9 – Biotechnology & Biosystems Engineering)

With the advent of Big Data, information is facing new, potentially more damaging, security threats. The current trend to enhance data protection is to use increasingly complex mathematical algorithms to encrypt information. This approach requires exponentially growing amounts of data, time and power resources. REMINDS proposes a radically new concept to boost data security: to act directly at material level, i.e. in the way information is stored. The project is built on the disruptive idea of using voltage to activate/deactivate magnetism via strain or ion migration effects and it tackles novel strategies to control the mutual interactions between ferromagnetic (FM), antiferromagnetic (AFM) and ferroelectric (FE) materials. While data written in ferromagnets can be read using conventional heads, AFM and FE materials are invisible to magnetic sensors due to their lack of magnetic stray fields (methods to read sub-200 nm AFM or FE domains are complex and often destructive). REMINDS will develop advanced engineering protocols to (i) transfer information from FM to AFM or FE materials, (ii) keep the data hidden in the AFM or FE layers while the FM state is switched off and (iii) retrieve the information whenever deemed necessary. Neuromorphic-inspired layouts will be used to selectively apply these protocols to specific memory units that will incorporate stochastic physical phenomena. This will be the basis of new energy-efficient proof-of-concept data protection designs whose working principle will be tested at lab scale for potential applications in anti-counterfeiting and anti-hacking technologies. REMINDS is expected to revolutionize magnetoelectricity, exploiting voltage-programmable magnetism to an unprecedented extent and forging an entirely new paradigm in data security. Its outcomes will bring ground-breaking scientific contributions to the fields of magnetism, spintronics, piezotronics and flexible electronics, and will have a huge socio-economic impact.

Jordi Sort – Universitat Autònoma de Barcelona (UAB)
AdG 2021 – (PE11 – Materials Engineering)

Even though the MYC oncogene is a “most-wanted” target in cancer therapy, no MYC inhibitor has yet reached clinical approval. The applicant has developed Omomyc, the first MYC-inhibiting mini-protein to have successfully completed a Phase Ia clinical trial. The goal of this proposal is to maximise the use of this compound, as both a therapeutic and study tool, opening new lines of research in different aspects of MYC biology.
To start with, since Omomyc cannot efficiently cross the blood brain barrier, excluding it from use in brain malignancies or brain metastases, in Aim 1, we propose to validate its efficacy when delivered intracranially by different means, including osmotic pumps and hydrogels, as well as to test its delivery by intracarotid injection, in glioblastoma and brain metastases.
Then, in Aim 2 and 3, we will explore its combination with personalized medicine, namely PARPi and KRASi, respectively. These 2 aims are derived from two pillars of MYC biology: its role in DNA damage response and the paradigm of oncogene cooperation. Aim 2 will allow us to shed light on the role of MYC in homologous recombination and resistance to PARPi, while Aim 3 will deliver on the molecular mechanisms underlying the cooperation of RAS and MYC in multiple tumour types, where their combined inhibition could represent an unprecedented therapeutic opportunity.
Finally, Aim 4 will focus on the characterisation of cancers such as Small Cell Lung Cancer and Gastrointestinal Stromal Tumours that have the peculiarity of being defective for MAX – MYC’s natural partner – but that recapitulate a MYC-dependent tumour phenotype, likely driven by other members of the MYC network, whose function could also be hindered by Omomyc treatment.
Notably, each of the aims explores new aspects of MYC biology, tracing new lines of research around the most deregulated oncogene in human tumours as well as having immediate translational applicability in upcoming clinical trials of Omomyc.

Laura Soucek – Vall d’Hebron Institut de Recerca (VHIR)
AdG 2023 – Life Sciences (LS7 – Prevention, Diagnosis and Treatment of Human Diseases)

GAPT – Geometric Analysis and Potential Theory

This project aims to solve several long standing questions in geometric analysis by combining techniques from harmonic analysis, geometric measure theory, and free boundary problems. These questions deal with harmonic measure and caloric measure, square functions and rectifiability, and some related free boundary problems. A common feature is that their study involves multiscale methods from Littlewood-Paley theory and quantitative rectifiability. Harmonic measure is a basic tool for the solution of the Dirichlet problem for the Laplace equation. The study of this notion is an old question which goes back to the 1910’s, at least. Recently there have been some striking advances on this topic, in part motivated by the deeper understanding of the connection between Riesz transforms and rectifiability. However, there are still related open compelling questions that this project aims to explore. The main one consists of finding a sharp bound for the Hausdorff dimension of harmonic measure. Other challenging questions arise in the parabolic setting, where the connection between the caloric measure associated with the heat equation and parabolic rectifiability is not well understood. Also, the study of the Lipschitz removability for the heat equation is more difficult than in the case of the Laplace equation. Another exciting topic that will be studied by this project deals with the relationship between rectifiability, square functions, and some free boundary problems. An important question concerns the characterization of the L^2 boundedness of Riesz transforms in terms of the Jones-Wolff potential, essential to understand the behavior of Lipschitz harmonic capacity under bilipschitz maps. Square functions, techniques of quantitative rectifiability, and monotonicity formulas from free boundary problems also appear in the study of the blowups of the singular set in the two phase problem for harmonic measure and in problems of unique continuation at the boundary.

Xavier Tolsa – Universitat Autònoma de Barcelona
AdG 2020 – PE1

EpiFold – Engineering epithelial shape and mechanics: from synthetic morphogenesis to biohybrid devices

All surfaces of our body, both internal and external, are covered by thin cellular layers called epithelia. Epithelia are responsible for fundamental physiological functions such as morphogenesis, compartmentalization, filtration, transport, environmental sensing and protection against pathogens. These functions are determined by the three-dimensional (3D) shape and mechanics of epithelia. However, how mechanical processes such as deformation, growth, remodeling and flow combine to enable functional 3D structures is largely unknown. Here we propose technological and conceptual advances to unveil the engineering principles that govern epithelial shape and mechanics in 3D, and to apply these principles towards the design of a new generation of biohybrid devices. By combining micropatterning, microfluidics, optogenetics and mechanical engineering we will implement an experimental platform to (1) sculpt epithelia of controlled geometry, (2) map the stress and strain tensors and luminal pressure, and (3) control these variables from the subcellular to the tissue levels. We will use this technology to engineer the elementary building blocks of epithelial morphogenesis and to reverse-engineer the shape and mechanics of intestinal organoids. We will then apply these engineering principles to build biohybrid devices based on micropatterned 3D epithelia actuated through optogenetic and mechanical control. We expect this project to enable, for the first time, full experimental access to the 3D mechanics of epithelial tissues, and to unveil the mechanical principles by which these tissues adopt and sustain their shape. Finally, our project will set the stage for a new generation of biohybrid optomechanical devices. By harnessing the capability of 3D epithelia to sense and respond to chemical and mechanical stimuli, to self-power and self-repair, and to secrete, filter, digest and transport molecules, these devices will hold unique potential to power functions in soft robots.

Xavier Trepat – Institut de Bioenginyeria de Catalunya (IBEC)
AdG 2019 – Physical Sciences & Engineering (PE8)

EVOCLIM – Behavioral-evolutionary analysis of climate policy: Bounded rationality, markets and social interactions

Distinct climate policies are studied with incomparable approaches involving unique criteria and impacts. I propose to unite core features of such approaches within a behavioral-evolutionary framework, offering three advantages: evaluate the effectiveness of very different climate policy instruments in a consistent and comparative way; examine policy mixes by considering interaction between instruments from a behavioral as well as systemic perspective; and simultaneously assessing policy impacts mediated by markets and social interactions. The key novelty is linking climate policies to populations of heterogeneous consumer and producers characterized by bounded rationality and social interactions. The resulting models will be used to assess the performance of policy instruments – such as various carbon pricing and information provision instruments – in terms of employment, equity and CO2 emissions.

The approach is guided by 5 goals:

(1) test robustness of insights on carbon pricing from benchmark approaches that assume representative, rational agents;
(2) test contested views on joint employment-climate effects of shifting taxes from labor to carbon;
(3) examine various instruments of information provision under distinct assumptions about social preferences and interactions;
(4) study regulation of commercial advertising as a climate policy option in the context of status-seeking and high-carbon consumption; and
(5) explore behavioral roots of energy/carbon rebound.

The research has a general, conceptual-theoretical rather than a particular country focus. Given the complexity of the developed models, it involves numerical analyses with parameter values in realistic ranges, partly supported by insights from questionnaire-based surveys among consumers and firms. One survey examines information provision instruments and social interaction channels, while another assesses behavioral foundations of rebound. The project will culminate in improved advice on climate policy.

Jeroen van den Bergh – Universitat Autònoma de Barcelona (UAB)
AdG2016 – SH2 – Social Sciences & Humanitites – Human Mobility, Environment & Space

FastTrack – Photons and Electrons on the Move

The conversion of sunlight photons to electrons is the essence of the natural photosynthesis that powers life. Dedicated antennas funnel the sun’s energy towards reaction centres. Amazingly, nature reaches almost perfect photon-to-electron conversion efficiency, while it regulates down at high light level for protection and survival.
How does nature dynamically re-organize the membrane architecture, its packing, order, diffusion, on light stress? Which pathways are taken to charge separation? What is the role of fluctuations, coherences, color and vibrations?
My group recently succeeded in first detection of the fs spectral progression of a single exciton, the nanoscale tracking of electron transport and reveal energy disorder of a single photosynthetic complex. These pioneering results, together with our expertise in fs pulse control and nanoimaging, set the grounds to now address photosynthetic light-to-charge transfer in real nanospace and ultrafast. Specific objectives are:
Energy transport on the nanoscale: tracking spatiotemporal membrane transport by super-resolved transient optical microscopy and nanophotonic light localization: to reveal disorder and quantify diffusion.
Light to charge: photo-current detection of the energy flow: by ultrafast photo-thermoelectric graphene and photo-electrochemical detection I will probe charge separation of the reaction center directly, quantify rate and efficiency.
Multidimensional spectra on the nanoscale: by collinear 2D spectroscopic imaging with photocurrent and fluorescence detection, I will map the development of the energy landscape, at special membrane spots, ultimately on a single complex.
Functional imaging: visualize the dynamic light-response of the membrane architecture, the changes in packing density, (dis)order, diffusion and pathways to charge separation.
The novel tool-set of FastTrack and the insights on nature’s energy strategies are directly relevant for artificial photosynthesis and solar technology.

Niek van Hulst – Institut de Cièncis Fotòniques (ICFO)
AdG2021 – PE4 – Physical Sciences & Engineering – Physical & Analytical Chemical Sciences

A grammar of collocations

The language of native speakers is highly idiosyncratic. Especially collocations (natural word pairings such as ‘make a decision’ or ‘strong tea’) dominate our speech. In lexicology, collocations are typically seen as prefabricated units that must be memorised by language learners. Yet small-scale studies have shown that their being prefabricated does not mean that their construction is ad hoc. The ERC-funded MaPPLexiC project employs deep neural models for collocation recognition and classification as cognitive models, analysing their internal patterns to uncover a ‘grammar of collocations’. With a multilingual scope spanning Germanic, Romance, Finno-Ugric and Slavic languages, MaPPLexiC seeks to identify both universal and language-specific rules. Its findings will advance linguistic theory, enhance learning and translation tools, and help support under-resourced languages.

Objective of the project:

MaPPLexiC aims to fill the gap in modern language theories concerning the interpretation and description of one type of idiosyncratic word constructions that stands out in terms of its frequency of use and as a measure of language proficiency, namely lexical collocations, and refute the wide-spread assumption that their production is ad hoc and therefore cannot be described in systematic terms. Inspired by the dramatic advances in Deep Neural Networks (DNNs) MaPPLexiC considers a lexical collocation identification and classification DNN as a cognitive model, whose internal neuron activation vectors during the assessment of the collocation status of a given word combination can be translated into interpretable semantic, contextual, and socio-cultural features of the collocation elements and generalized into “collocation production principles” that dictate which features lexical items must possess to form a lexical collocation. In other words, what MaPPLexiC targets is a lexical collocation grammar. For this purpose, the Project will adapt and advance state-of-the-art techniques for the derivation of interpretable features from DNN’s activation vectors of individual lexical collocation samples and neural clustering techniques that will facilitate the generalization of the obtained “profiles” for the individual samples to more generic collocation production principles. Considering that collocation construction differs from language to language, the Project has a strong multilingual orientation. The investigation will be carried out on pairs of Germanic (English, German), Romance (French, Spanish), Finno-Ugric (Finnish, Hungarian), and Slavic (Czech, Russian) languages. The collocation profiles of translation-equivalent collocation samples and the language-specific collocation production principles will be contrasted with the goal to develop cross-language collocation production transfer techniques, which will highly benefit collocationally under-resourced languages.

Leo Wanner – Barcelona Supercomputing Center (BSC)
AdG2024 –  SH4 – Social sciences & humanities – The Human Mind and its Complexity

The overarching goal of the GravNet project is to develop, test and deploy a novel experimental platform that could enable the first detection of gravitational waves (GWs) in the frequency range of MHz to GHz, thereby providing a new and unique window into astrophysical processes that have so far eluded observation. The first detection of gravitational waves by LIGO in 2015 ushered in a new era of fundamental physics. Since then, a network of ground-based GW interferometers has probed the frequency range from 10 Hz to 10 kHz, detecting nearly a hundred mergers of black-hole and neutron-star binaries. In 2023, a signal at much lower frequency, in the nHz band, was detected by timing radio signals from pulsars. The race is now on to explore other bands. Of particular interest in this context is access to the MHz-GHz range, as in this range signals may be generated copiously by events such as primordial-black- hole-merger, by the dynamics of ultra-light dark matter overdensities or violent phenomena in primordial cosmological times – all processes related to some of the most pressing open questions about our Universe.

The use of cavities in strong magnetic fields has been identified as one of the most promising techniques to search for high-frequency gravitational waves. So far, efforts were focused on cavities with small volumes that are tuned to search for axion-like particles. By contrast, the GravNet scheme is based on combining different technologies and methodological approaches to measure synchronously cavity signals from multiple devices in magnetic fields operated as a network across Europe, increasing the sensitivity to high frequency GWs (HFGWs) by several orders of magnitude compared to current approaches. In this way, GravNet will open up a new, vast parameter space for gravitational-wave searches and might be the enabling step towards the first detection of HFGWs – with the potential to revolutionize our understanding of the Universe.

Diego Blas – Institut de Física d’Altes Energies (IFAE)
SyG 2024

Together with:

• Matthias Schott, Rheinische Friedrich-Wilhelms-Universität Bonn, Germany
• Dmitry Budker, Johannes Gutenberg-Universität Mainz, Germany
• Claudio Gatti, Istituto Nazionale di Fisica Nucleare, Italy

Focal brain disorders, including stroke, trauma, and epilepsy, are the main causes of disability and loss of productivity in the world, and carry a cumulative cost in Europe of about 500 billion euro/year. Now, physicians diagnose and treat these conditions as if they were caused by local dysfunction due to the pathological process. However, there is growing evidence that, in most neurological and psychiatric disorders, clinical symptoms reflect widespread network abnormalities. Normalization of such network abnormalities through “circuit-based” stimulation would therefore improve function. However, this form of therapy is currently limited by numerous factors: lack of knowledge about the underlying mechanisms and their behavioural relevance; inability to map these abnormalities onto single patients; and, most importantly, a principled understanding of where and how to stimulate the brain to produce functional recovery.

‘NEMESIS’, from Ancient Greek as “give what is due”, aims to “give an injured brain what is missing”, i.e., restore through stimulation normal activity in dysfunctional brain circuitries. By synergizing people, concepts, and technologies, NEMESIS will first characterize the effects of focal injury at multiple spatial and temporal scales (from whole brain to local circuits). Through the combination of observational (e.g., fMRI, EEG, calcium imaging, LFPs) and causal methods (e.g., electro-magnetic stimulation, optogenetics) NEMESIS will test the hypothesis that disconnected networks lie in a “sleep-like state” that impairs communication. Thirdly, NEMESIS will create whole brain models of structure/function to predict the effect of individual lesions and simulate novel stimulation protocols aimed at “re-awakening” the disconnected brain. Finally, proof-of-concept interventions that combine circuit-based stimulation and behavioural training, guided by modelling and animal studies, will be tested to restore normal activity, and so give back what is due.

Gustavo Deco – Universitat Pompeu Fabra (UPF) & Mavi Sánchez – Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
SyG 2022

Endothelial cells (ECs) form a dynamic monolayer lining the lumen of vessels. While single-cell data have revealed high degrees of heterogeneity amongst ECs at the inter- and intra-organ levels, the prevailing notion has long been that vessels themselves are composed of largely similar ECs.
Instead, data from our labs challenge this view by showing that vessels are built of highly diverse ECs displaying different behavioral properties, a feature we term intravessel EC behavioral mosaicism. While these findings are promising, there is still much to learn about the range of behavioral variability among ECs within vessels and how this intricate mosaic of behaviors is orchestrated to optimize vascular function.
Building on our past achievements, we now aim towards novel directions- to push forward a fresh conception of vessels, as mosaic composites of specialized ECs. Here, we will integrate our synergistic expertise in live imaging, sophisticated genetic approaches, and spatial omics to map EC behaviors in zebrafish and mice. In addition, we will harness oncogenic mutations causing vascular malformations in humans to investigate how they alter the behavioral map. Finally, we will decode mechanisms of vessel tolerance and co-optation in response to stochastic expression of mutations to understand how vessels cope with EC mosaic behaviors. The important and unique aspects of our approach are the focus on in vivo dynamics and the cross-animal and organ comparisons, which will provide much needed knowledge on vessel architecture and function, making substantial advances at the frontier of vascular biology. Overall, we envision that shifting the paradigm of vessel heterogeneity to behavioral mosaicism will provide a better understanding of vascular-related pathologies and will lay the foundation for improving vascular therapies by targeting specific EC subsets. Moreover, we expect to offer means to understand other diseases involving mosaic responses, including cancer.

Mariona Graupera – Institut de Recerca contra la Leucèmia Josep Carreras (IJC)
SyG 2024

Together with:

• Karina Yaniv, Weizmann Institute of Science, Israel
• Valentina Greco, Yale University, USA

Mapping the path from immune cell to cancer

B-cells are highly dynamic lymphocytes in the immune system. When B-cells bind with an antigen, a chemical signal tells them to divide many times, resulting in an army of B-cells that ultimately produce thousands of antibodies in seconds. B-cells are also at the root of chronic lymphocytic leukaemia (CLL), the most common form of leukaemia in Western countries. CLL is characterised by abnormal growth and proliferation of neoplastic B-cells. EU-funded scientists are studying the maturation of thousands of healthy and diseased B-cells with the ambitious goal of characterising CLL molecular biology throughout the course of the disease process.

Objective of the project:

Unbiased analyses of the molecular make up of single cells are revolutionizing our understanding of cell differentiation and cancer. Over the last years, our groups have characterized the molecular features of normal B-cell subpopulations and of pools of leukemic cells from chronic lymphocytic leukemia (CLL), the most frequent leukemia in the Western world. These analyses have revealed that CLL subtypes are related to different B-cell maturation stages, and that they can show a complex subclonal architecture. Such subclonality is dynamically modulated during the course of the disease, and has deep implications in CLL biology, clinical aggressiveness and treatment responses. In this scenario, BCLL@las aims at deciphering the origin and molecular anatomy of CLL during the entire life history of the disease by generating genetic, transcriptional and epigenetic maps of hundred-thousands of single cells across locations, time points and individuals. We plan to fulfill four major objectives: 1) To generate a comprehensive atlas of normal B-cell maturation, 2) To understand the initial steps of neoplastic transformation through the analysis of minute B-cell monoclonal proliferations in healthy individuals, 3) To decipher the cellular diversity and clonal architecture of CLL at diagnosis, and 4) To characterize the single-cell subclonal dynamics of CLL during disease evolution and treatment response. To reach these goals, BCLL@las gathers together four teams with complementary expertise in B-cell biology, clinics and pathology of CLL, genomics, transcriptomics, epigenomics, sequencing technologies, single-cell profiling and computational biology. This, together with the richness of the available CLL samples and the technical and analytical depth of BCLL@las shall lead to unprecedented insights into the origin and evolution of cancer in the precision medicine era.

Holger Heyn – Centre Nacional d’Anàlisi Genómica (CNAG), Spain
Iñanki Martín-Subero – Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (FRCB – IDIBAPS), Spain
SyG 2018

Together with:

• Elias Campo, Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (FRCB – IDIBAPS), Spain
• Ivo Gut, Centre Nacional d’Anàlisi Genómica (CNAG), Spain

While mental states are constantly fluctuating, these fluctuations are usually mild. For approximately 22 million people in Europe, however, they can tip into unpredictable turbulence, resulting in psychotic episodes that often recur. A team of international researchers, based in the Netherlands, Norway, Spain and Switzerland, hypothesizes that this mental turbulence is reflected by what they call “the delta of language” – measurable changes in language and the brain. With the help of large language models, which give computers the ability to comprehend and interpret human language, and with high-frequency brain imaging, they want to repeatedly measure the linguistic and neurobiological changes during different states of psychosis – from the acute phase to remission.

The aim of their project DELTA-LANG is to build a personal and neurobiologically plausible index of phase-change: when people with psychotic episodes go from a remission to a psychotic relapse. The capacity to understand and detect such phase-changes early enough, similar to our capacity to forecast a thunderstorm, would be a major advance in public health – since unlike thunderstorms, psychosis can be prevented. Moreover, a breakthrough in this field could potentially have wide-ranging implications not only for managing recurring psychotic episodes but also for other mental diseases.

Wolfram Hinzen – Universitat Pompeu Fabra (UPF)
SyG 2023

Together with:

• Iris Sommer, University Medical Center Groningen (UMC Groningen), Netherlands
• Philipp Homan, Universität Zürich (UZH), Switzerland
• Brita Elvevåg, UiT Norges arktiske universitet, in Tromsø, Norway

How can we sustain human well-being within planetary boundaries? What policies and provisioning systems could enable societies to prosper without growth? What politics and alliances are necessary for seeing post-growth policies through, and how can the public be engaged in them? What new scientific paradigm could answer such questions?

Societies face multiple intertwined crises. Bold alternatives are sorely needed. This project develops frameworks for ‘Post-Growth Deals’, from empirical research through to practical applications. First, we develop equitable North-South convergence scenarios, modelling human well-being achievement in all countries within planetary boundaries. Second, we articulate post-growth policy packages for the Global North and South, assessing their political acceptability and modelling their effects. Third, we develop models of provisioning systems to ensure future populations have adequate energy, food, shelter, health and social security. Fourth, we learn from political movements, studying politics and alliances that could bring post-growth transitions forward. Fifth, we identify practical steps to bring Post-Growth Deals to life, working with four representative communities to co-produce knowledge and action on the ground.

The potential gains of this research are immense: post-growth transitions may unlock a far more ecologically stable and socially prosperous future than current trajectories lead to. REAL brings a paradigm shift moving post-growth science from economics to sustainability studies. We propose a new trans-disciplinary ‘5Ps of post-growth’ science, grounded in resource/energy modelling, political-economy and socio-political analysis – a skill-set that no single researcher or team presently possesses. The PIs are leaders in their fields and bring complementary expertise in: modelling of provisioning systems (JST), political economy and North-South relations (JΗ), and the politics of socio-environmental transformations (GK).

Giorgos Kallis and Jason Hickel –  Institut de Ciència i Tecnologia Ambientals de la Universitat Autònoma de Barcelona (ICTA-UAB)
SyG 2022

Together with:

• Julia Steinberger, University of Lausanne, Switzerland

The goal of SKIN2DTRONICS is to demonstrate the large scale integration (LSI, transistor count larger than 1000) of soft and thin (skin-like) electronic devices on ultra-flexible substrates, capable of conformally adapting to any rough and curved surface. This vision will be realized by atomically thin two-dimensional materials (2DMs) that possess compelling properties for this application: high electronic performance, environmental stability, low toxicity and cytoxicity, and extreme resilience to mechanical deformations.  With the increasing pressure towards ubiquitous electronics (wearables, Internet-of-Things, smart patches, etc.) it is urgent to develop electronics that can be easily integrated on the surface of everyday objects and, in the case of health monitoring applications, on a variety of rough biological surfaces. Today’s conformal electronics is mainly based on conformal sensors with flexible and stretchable electrodes interfaced to bulky silicon chips, responsible for processing. This approach is prone to mechanical failures, especially at the solderings, as the connection between the conformal and solid components remains very challenging.  The research will rely on the complementary conjuncture of four fields: sensors, 2D-based electronics, flexible electronics and biomedical engineering that the PIs of the consortium bring, each of them recognized experts in their respective fields and with a valuable experience in leading ERC projects.

Kostas Kostarelos – Institut Català de Nanociència i Nanotecnologia (ICN2)
SyG 2024

Together with:

• Gianluca Fiori, Università di of Pisa, Italy
• Andrés Castellanos-Gómez, Insntituto de Ciencias de Materiales de Madrid (ICMM – CSIC), Spain
• Andres Kis, École Polytechnique Fédérale de Lausanne (EPFL), Switzerland 

LiquOrg – Do liquid crystal-like phases of proteins organize membrane compartments?

We are in the midst of a revolution in our understanding of the internal organization of cells. In the 1950s we learned that lipid bilayer-based membranes serve as containers (organelles) within the cytoplasm. Now we are learning that liquid-like “membrane-less” organelles i.e. without any container, self-assemble based on “liquid-liquid” phase separations. We propose the seemingly radical idea that membrane-bounded organelles– like their membrane-less counterparts- are stabilized or even templated by analogous phase separations of their surface proteins into largely planar liquids akin to liquid crystals. Our unique Synergy team is organized specifically to test this “liquid crystal hypothesis” on the cell’s secretory compartments – ER exit sites (ERES) and the Golgi stack – by employing our complementary skills in physics, physical chemistry, biochemistry and cell biology. We hypothesize based on pilot experiments evidence that the ERES and Golgi self-organize as a multi-layered series of adherent liquid crystal-like phases of “golgin” and similar proteins which surround and enclose their membranes. Their differential adhesion and repulsion would specify the topology and dynamics of the membrane compartments. If this is true, it will literally rewrite the history of cell biology. We will test the ‘liquid crystal’ hypothesis directly, systematically, and quantitatively on an unprecedented scale to either modify/disprove it or place it on a firm rigorous footing. Experiments (Aim 1) with 13 pure golgins in cis and trans pairwise combinations will establish their foundational physical chemistry. Surgically engineered changes in golgins/ERES proteins will alter the rank order (hierarchy) of their affinities for each other and link phase separation physics to cell biology (Aim 2) and be used to establish the structural basis of phase separations and their specificity, and the potential for self-assembly of wholly synthetic biological organelles (Aim 3).

Vivek Malhotra – Centre de Regulació Genòmica (CRG)
SyG 2020

Successful defence against invaders is critical for survival of eukaryotic cells. Microbes have developed many strategies to subvert host organisms which, in turn, evolved several innate immune responses to counterattack. As major lipid storage organelles of eukaryotes, lipid droplets (LDs) are an attractive source of nutrients for invaders. Pathogens induce and physically interact with LDs and the current view is that they ‘hijack’ LDs to draw on substrates for host colonisation. We recently challenged this dogma by demonstrating that LDs are endowed with a regulated protein-mediated antibiotic activity. Our work intro-duced the new concept that dependence on host nutrients is a generic ‘Achilles’ heel’ of intracellular pathogens and LDs a chokepoint harnessed by innate immunity to organise a front-line defence. Here, we have formed a multidisciplinary group combining complementary knowledge and transdiscipli-nary expertise to investigate the hypothesis that LDs are innate immunity hubs sensing infection and di-rectly confronting invaders. We will characterise, in cells and animals, how LDs efficiently coordinate and precisely execute a plethora of immune responses such as killing, signalling and inflammation. High-throughput proteomics and lipidomics will identify defensive players. 3D electron tomography and confo-cal microscopy will be combined with proximity labelling strategies and biochemical methods to get un-precedented understanding of host LD-pathogen dynamics. The successful pathogen Mycobacterium tuber-culosis will be used to test the medical significance of our findings and unravel bacterial mechanisms of resistance to LD-mediated defences. Characterisation of these novel innate immune systems will be paradigm-shifting in immunology, physiol-ogy and cell biology. In the age of antimicrobial resistance and viral pandemics, unravelling how eukaryot-ic LDs fight and defeat dangerous microorganisms will inspire new anti-infective therapies.

Albert Pol – Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
SyG 2022

Do the laws of quantum physics hold for massive objects of arbitrary size? Q-Xtreme will address this very important question by testing the quantum superposition principle at unprecedented macroscopic scales: we will place a levitated object in two locations at once, separated by a distance comparable to its size. Experimental confirmations of macroscopic quantum superpositions started as early as 1927, using electrons, and have today reached the size of organic molecules containing thousands of atoms. Q-Xtreme will bring macroscopic quantum physics to an entirely new level by preparing macroscopic quantum superpositions of objects containing billions of atoms, pushing current state-of-the-art by at least five orders of magnitude in mass.

This goal will be achieved by using a radically new approach: quantum controlling the center-of-mass motion of a levitated nanoparticle (a solid-state object of few hundred nanometers) in ultra-high vacuum by using optical, electrical and magnetic forces. Q-Xtreme requires cutting-edge expertise in photonics, nanotechnology, optoelectronics, and quantum technology, which this Synergy Group uniquely combines. The achievements of Q-Xtreme are only possible by the combined proficiency in both fundamental science and engineering of this Synergy Group.

The implications of Q-Xtreme are far-reaching. Testing the quantum superposition principle at unprecedented mass regimes opens the door to experimentally study the interplay of quantum physics and gravity, as well as dark matter and dark energy models. These macroscopic quantum superpositions will also give rise to ultrahigh sensing accuracies, with applications in inertial force sensing, measurements of short-range interactions and gravitational physics.

Oriol Romero Isart – Institut de Ciències Fotóniques (ICFO)
SyG 2020

Together with:
Lukas Novotny, Swiss Federal Institute of Technology Zurich (ETH Zurich)
Markus Aspelmeyer, Swiss Federal Institute of Technology Zurich (ETH Zurich)
Romain Quidant, University of Vienna

CARBOCENTRE – Activity-Based Profiling of Glycoprocessing Enzymes for Human Health and a Sustainable Society

Enzymes that produce and degrade oligosaccharides and glycoconjugates are present in all kingdoms of life. The ability to visualize, modulate and understand these carbohydrate-active enzymes (CAZymes) therefore offers great potential for human health and sustainable industries. To provide a “disruptive” shift in our understanding, we adopt in this proposal a multidisciplinary approach combining structural biology, enzymology, computational chemistry, organic synthesis, and chemical biology, with major leaders in these fields part of our CARBOCENTRE Synergy Team. Three fundamental strands will specifically target and ‘capture’ glycoprocessing enzyme active sites. Biochemical and 3-D structural analyses will inform computational dissection of the reaction coordinate of key enzymes for human health and biotechnology processes. Building on our founding work on retaining glycosidases we will also target inverting glycosidases and glycosyltransferases. Following fundamental analyses, our probes will feed research in two major application domains of human health and biotechnology: 1. To provide visualization, diagnosis, and inhibitor assays and clinical lead compounds for enzymes in cancers and genetic diseases (lysosomal storage disorders). 2. To explore the natural diversity of CAZymes and to discover, quantify and optimize new enzymes for food and household applications and for biomass conversion to biofuels. In an iterative cycle, structural biology and enzymology (Davies, York), will inform, through structures of enzymes and enzyme-inhibitor complexes, theoretical and computational chemistry (Rovira, Barcelona), which in turn will guide the design and synthesis (Overkleeft, Leiden), of inhibitors and activity-based probes for ensuing chemical biology studies in the domains of biomedicine and biotechnology.

Carme Rovira i Virgili – Universitat de Barcelona (UB)
SyG 2020

Rebuilding life’s most important mechanism

A cell first goes through a radical transformation before it splits. Cell division is one of the most fundamental processes in life. The ERC-funded BIOMECANET project will study this mechanism that involves out-of-equilibrium chemistry of many components. It will rebuild the mechanism, reassembling the engine of division. Specifically, the project’s goal is to unravel this interplay by re-engineering it in vitro and by modelling it in silico. It will analyse the emergence of complex life-like biological functions by combining these reconstituted networks, integrating temporal control and mechanical forces. This will elevate the scale and scope of in vitro reconstitutions.

Objective of the project:

Cellular and sub-cellular organisation at the micrometre length scale ultimately reflects the activity of molecular networks that harness chemical energy to perform precise mechanical work, create functional spatial gradients, and sustain timely temporal changes in molecular activities. In eukaryotic cell division, the biochemical oscillations of the cell cycle drive dramatic morphological changes of the cytoskeleton necessary for bi-orientation of chromosomes and for their subsequent delivery into two daughter cells. This mechanism is at the heart of biology, but it is poorly understood and hard to address because it involves out-of-equilibrium chemistry of many components and Brownian mechanics of the cytoskeleton. BIOMECANET’s extraordinarily ambitious goal is to unravel this interplay by re-engineering it in vitro and by modelling it in silico. To achieve this, BIOMECANET will mobilize an unrivalled catalogue of purified human proteins to reconstitute four fundamental and interlinked biochemical and mechanical protein networks: 1) the cell cycle oscillator with the spindle assembly checkpoint; 2) the metaphase spindle; 3) the chromosome bi-orientation machinery of kinetochores; and 4) the central spindle and its links with the actin cytoskeleton required for cell fission. Then, BIOMECANET will combine these reconstituted networks, integrating temporal control and mechanical forces to analyse the emergence of complex life-like biological function, thus elevating scale and scope of in vitro reconstitutions to an entirely new level. Crucial to the attainment of BIOMECANET’s long-term goals is the synergetic alliance of two biochemists having pioneered different types of biochemical reconstitutions in the complementary areas of cell cycle and chromosome biology (Musacchio) and the cytoskeleton (Surrey), and a theoretician having pioneered physically faithful modelling and simulation of intracellular systems (Nédélec).

Thomas Surrey – Centre de Regulació Genòmica (CRG)
SyG 2020

Together with:

• Andrea Musacchio, Max Planck Society, Germany
• Francois Nedelec, University of Cambridge, United Kingdom

Alternative splicing (AS) of mRNA precursors plays important roles in tissue-specific gene regulation and biological regulatory mechanisms, as it can radically alter protein expression, cell phenotypes and physiological responses. Altered splicing also contributes to disease mechanisms, ranging from neurodegeneration to cancer. Drugs modulating AS have recently provided the first therapy for Spinal Muscular Atrophy, a common genetic disorder, illustrating the huge potential for treating many other diseases of unmet need, if only we understood the mechanisms controlling splice site selection and how to regulate them with small molecules.

Unfortunately, despite decades of research, a comprehensive understanding of the mechanisms that control specificity of AS is lacking. This gap in basic knowledge prevents opportunities to harness splicing modulators as tools to study gene function, novel therapeutics, or other biotech applications. This Project addresses head-on the major technical challenges that have limited progress in the AS field. Building on extensive preliminary data, we will use a multidisciplinary approach that combines chemical, structural, cellular, systems biology and machine learning to characterize mechanisms of splice site selection and identify targets for modulating these mechanisms using tool compounds. The outcomes will define key regulatory sequences, splicing factors and molecular interactions involved, thereby illuminating how the splicing machinery efficiently accommodates, yet also discriminates between, a wide range of splice site sequences. This will enable future applications harnessing splice site selection. Our primary goal is to answer the central question, ‘Is it generally possible to modulate splicing with high specificity using small molecules?’ Success will transform our basic understanding of human gene expression and unleash major opportunities for Pharma to develop new therapeutics.

Juan Valcárcel – Centre de Regulació Genòmica (CRG)
SyG 2022

SmolSUB is a key tool in the progress of organic electronic devices (OEs). SmolSUB promotes the creation/discovery of new OEs, basic skeletons in organic field-effect transistors, (bio)sensors, organic light-emitting diodes (OLEDs), organic solar cells (OSCs), soft-robotics, among others. SmolSUB presents a new, greener, and low-cost vision (in terms of materials, waste and energy required) in the testing of organic electronic materials on substrates of interest, using a simple methodology, applicable at different scales (basic laboratories and industry), inclusive with other existing ones and of fast execution, projecting a profound change in how to create, analyse and apply new OEs (from the combination of materials to their applications).
SmolSUB is based on strategically designed sublimation devices, which under mild and eco-friendly conditions, allow the direct deposition of useful organic molecules on substrates of all kinds. The project foresees its usefulness in the creation of wearable electronics, imperceptible electronics, and smart packaging, among other applications, and will enhance the creation of new devices with flexibility and stretchability properties, born from the molecule+substrate synergy.
SmolSUB seeks the validation of this methodology and the launch and real projection of commercialisation of the products presented here (through spin-offs or agreements with companies).

Núria Aliaga – Institut de Ciències de Materials de Barcelona (ICMAB-CSIC)
PoC – 2023 PE4

Cities in the Global North are increasingly adopting nature-centered and other green infrastructure interventions to respond to climate risks and impacts and enhance their adaptation and resilience capacity. Yet, plans for such green infrastructure (GI) and other urban greening interventions tend to underestimate risks of displacement for lower-income and minority residents – what myself and others have previously called green climate gentrification. Despite increasing recognition of this process and concerns for the displaced, few municipal green interventions are coupled with social provisions (such as social housing; resident-driven economic development schemes) to protect residents from displacement. Yet, predicting and preventing green gentrification is the only way to build a green resilience agenda that upholds the stated social and environmental goals of such plans and avoid green paradoxes born out of urban renaturing projects and which municipalities have expressed commitment to avoid.
In this POC, I propose to further analyze the social equity impacts of climate adaptation and green resilience efforts and build on my GreenLULUs ERC in order to (a) create a replicable, interactive community- and policy-driven predictor index, tool, and analysis for green gentrification in the context of planned green climate-centered infrastructure and (b) test the early development of an actionable, pilot municipal policy and planning instrument, such as a climate-adaptation focused community land trust, a municipal green bond program for equitable climate resilience, a community-based stewardship fund, or green minority-owned green business seed grants (among others) to prevent green climate gentrification. These tasks will be decided and built in partnership with municipal governments and community groups based on pilot cities included in my finishing ERC project – Barcelona and Boston – so that this POC can support them in their work for more just green cities.

Isabel Anguelovski – Universitat Autònoma de Barcelona (UAB)
PoC – 2022 SH3

Targeting lipid metabolism for metastasis treatment

The spread of cancer cells from a primary site to distant organs accounts for 90 % of cancer-related deaths and remains largely incurable. Emerging evidence highlights the critical role of lipids in metastasis, which provide energy, membrane components, and activate signalling pathways that drive tumour progression. Notably, palmitic acid uniquely promotes metastasis by inducing lipid metabolism reprogramming and epigenetic remodelling. Beyond fuelling cancer cells, fatty acids also regulate protein lipidation, a key process in metastasis. The ERC-funded PalmitoMET project aims to develop inhibitors that target this lipid signalling pathway to treat metastasis. These inhibitors could become first-in-class drugs with significant therapeutic potential against metastases.

Objective of the project:

Despite recent breakthroughs in immunotherapy and cancer research, metastasis continues to be responsible for 90% of cancer related deaths. While surgical resection and adjuvant therapy can cure localized tumors, once tumor cells metastasize, cancer remains largely incurable. Increasing evidence indicates that lipids play a crucial role in the metastatic process by providing energy and membrane components required for cell migration and outgrowth, and also by triggering specific signaling cascades that prime cancer cells into a metastatic program (Martin-Perez et al., Cell Metabolism 2022). Importantly, we have found that palmitic acid, but not other fatty acids, promotes metastasis in a large number of tumors, and that metastatic initiating cells require a lipid metabolism reprogramming driven by an epigenetic remodeling (Pascual et al. Nature 2017; Pascual et al. Nature 2021). We have solid evidence that fatty acids not only promote metastasis by providing energy to metastatic cells (Delauney et al. Nature 2022), but also by specifically modulating protein lipidation. Thus, targeting this particular lipid signaling machinery may represent an unexplored solution to combat metastasis. PalmitoMET aims to identify novel molecules capable of inhibiting specific protein lipidation to treat metastasis in preclinical models, with the aim to bring them closer to the clinic. Inhibitors found during this project have the potential to become first-in-class drugs, making this project a high risk but high gain project, considering the very large and growing market we are addressing.

Salvador Aznar Benitah – Institut de Recerca Biomèdica (IRB Barcelona)
PoC2023 – LS4 – Life Sciences – Physiology in Health, Disease & Ageing

Novel nano-medicines to reduce chronic inflammation

Inflammation is a biological response to injury, infection and even threats like toxic chemicals. However, when the inflammation persists, or occurs in the absence of a threat, it can cause damage to cells and tissues and is associated with a wide range of chronic inflammatory diseases. The ERC-funded MAIN project aims to create new nano-medicines that will be used to identify anti-inflammatory treatments. The team will optimise the synthetic process enabling control of the primary sequence of the polymer, the nanomedicine’s size and its degradation processes. Candidates will be screened in vitro for selective targeting of macrophages and effective anti-inflammatory activity. The most promising will then be tested in vivo.

Objective of the project:

Our proposal is to create new nanomedicines for identifying anti-inflammatory therapies. Through the optimisation of synthetic procedures, we aim to control the primary sequence of the polymer, the size of the nanomedicine, and degradation profiles. High-content in vitro screening will be utilised to determine which formulations can most selectively target macrophages and have the strongest anti-inflammatory effect. To test the effectiveness of these formulations, we will collaborate with specialised research groups to conduct appropriate in vivo testing using various models of inflammation.

Giuseppe Battaglia – Institut de Bioenginyeria de Catalunya (IBEC)
PoC2023 – PE5 – Physical sciences & engineering – Synthetic Chemistry & Materials

A closer look at covalent drug design

The pharmaceutical industry has seen a surge in approved covalent drugs over the past 20 years. These drugs are designed to form stable, often irreversible bonds with specific disease targets, and rely on ‘chemical warheads’, electrophilic groups that react with amino acids in proteins, either reversibly or irreversibly. However, the effectiveness and safety of these warheads vary, necessitating the search for new options. The ERC-funded Cyclo-warhead project aims to explore a novel chemical warhead for developing kinase inhibitors – drugs that could revolutionise treatments for cancers and other diseases by targeting enzymes involved in cell growth and survival. This project could pave the way for the next generation of precision medicines.

Objective of the project:

Over the past two decades, the pharmaceutical industry has witnessed an exponential growth in approved covalent drugs. The majority of such drugs incorporate a chemical warhead, a mild electrophilic reactive functional group that forms covalent bonds in a reversible or irreversible manner with nucleophilic aminoacid residues. The aim of this proposal is to assess the viability of a new chemical warhead in the discovery of novel kinase inhibitors.

Marcos Gracía Suero – Institut Català de Investigació Química (ICIQ)
PoC2024 – PE5 – Physical sciences & engineering – Synthetic Chemistry & Materials

Recent advances in Next-Generation Sequencing (NGS) of nucleic acids (i.e. DNA or RNA) have transformed biology and medicine.
Today NGS is one of the main pillars of research in various biological disciplines, and it has already pervaded numerous fields of
applications ranging from clinics to the biotechnological industry. Given its versatility and high demand, the global market for
NGS is rapidly expanding, with the number of sequenced samples doubling every two years. However, while major advances in NGS
were mainly related to a rapid increase in sequencing throughput per machine, the preparation of sequencing libraries – the other
integral step of NGS, has largely remained unchanged. Currently, this step is the major financial and operational bottleneck for
sequencing projects, limiting the widespread adoption and utility of NGS. Current state-of-the-art solutions for overcoming these
problems either require high upfront costs and/or are laborious. We are developing a bioinformatics solution to these problems,
which minimizes the cost and time of library preparation. Our approach, called MultiSeq, allows designing a multiplexing strategy to
reduce the number of libraries followed by computational demultiplexing. We plan to extend the experimental proof of concept of
our method by applying it to broadly sequenced species. In addition, we will integrate our algorithms into a versatile computing
framework and develop a pilot project in an industrially relevant context. In parallel, we will perform market analysis and evaluate the
most suitable IP protection and commercialization strategies of our technology. If successful, MultiSeq will be a game-changing
approach that will impact sequencing technology and related industries by further democratizing the field of NGS and benefiting
both the scientific community and society.

Toni Gabaldón – Institut de Recerca en Biomedicina (IRB Barcelona) & Barcelona Supercomputing Centre (BSC)
PoC – 2023

6th generation (6G) mobile broadband communications will transform the communications industry, leading to high speed networks capable of linking integrated communication, sensing, and computing capabilities to fuse the physical, biological, and cyber worlds. However, 6G infrastructure will require a significant increase in data transfer rate (>10 times larger than current standards), ultra-low power consumption (<1pj/bit), and high reliability. 5G technology, originally designed for data rates up to 20 Gbps, cannot fulfill these requirements. The sub-THz spectrum (~100GHz-300GHz) could provide the required capacity for 6G short-range wireless links. On the other hand, Multiple-Input-Multiple-Output (MIMO) systems, consisting of multiple transmitting/receiving antennas, are a key element of 5G tech, dramatically increasing the spectral efficiency of the wireless link, multiplying the data transfer rate of the single TX/RX antenna system by the number of implemented channels. Developing a technology that can combine the advantages of the sub-THz spectrum and MIMO systems could yield short-range 6G wireless connectivity, significantly enhancing data rates, power consumption, and reliability. ICFO’s patented Antenna-integrated-Graphene-THz-Detector (AGTD) technology, providing ultrabroadband frequency operation, high speed (potentially >100GHz), high sensitivity, small footprint and low power consumption, represents an ideal solution able to meet all the requirements for the realization of a MIMO system operating at unprecedented frequencies. TERACOMM envisions the realization and the demonstration of the receiver module of a graphene-based wireless MIMO system able to reach data rates >100Gbps for short range applications. Industrial links, protection of intellectual property, and commercial exploitation will lie at the heart of the project from the outset, in order to maximize the potential for this technology to realize a significant social and economic impact.

Frank Koppens – Institut de Ciències Fotòniques (ICFO)
PoC – 2022 – PE3 – Condensed Matter Physics

Enzymes exhibit high efficiency, specificity, selectivity, biodegradability, non-toxicity, and the ability to function effectively under gentle biological conditions. These qualities render enzymes a sustainable and eco-friendly substitute for traditional catalysts within industrial settings. However, harnessing enzymes for industrial applications often necessitates extensive and costly experimental engineering efforts. Computational methods hold promise as potential solutions, but these have not yet demonstrated the ability to rapidly design highly efficient enzymes that mimic those found in Nature. As opposed to other methods, our computational approach developed in the previous ERC-STG can introduce active site and distal mutations that modulate the enzyme conformational dynamics, achieving increases in catalytic efficiency of up to 1000-fold. This project aims to exploit the proprietary technology developed in ERC-STG and ERC-POC for generating a set of patentable rationally designed enzyme kits focused on stereoselective carbon-carbon bond formation. KITZYME aims to create a spin-off for the exploitation of the new set of rationally designed enzyme kits as well as the proprietary technology developed for enzyme optimization. Both the enzyme kits and our technology are the cornerstone of the project, and will provide industries with a cost-effective, scalable, and environmentally sustainable solution.

Sílvia Osuna – Universitat de Girona (UdG)
PoC – 2023

Mucus is a defensive barrier that protects the underlying cells from pathogens and toxic compounds, although it also hinders the delivery of drugs whenever they are administered locally. There are different types of mucus-secreting tumours, such pseudomyxoma peritonei (PMP), that could benefit from more efficient transmucosal delivery of anti-cancer drugs. PMP is a rare disease and the most mucinous tumour type, thus it will be used as a proof of concept for this project. In fact, it is characterised by the production of abundant mucus in the peritoneal cavity and is treated with cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy, usually Mitomycin C. This approach has extended patient survival in some cases, but there is a significant proportion of recurrence, most probably due to the shielding effect of mucus. Therefore, there is an urgent need to offer new therapeutic strategies to PMP patients. Recently, Dr. Palmer’s lab has established a biobank of PMP patient-derived organoids and xenografts and has shown that some PMP patients present oncogenic BRAFV600E mutations, introducing a new druggable targeted mutation. In this proposal, Dr. Sánchez’s lab (IBEC), in collaboration with Dr. Palmer’s research group (VHIO), aims to use nanobots that will be loaded with Mitomycin C or Encorafenib (BRAF inhibitor) to treat PMP. These nanobots will not only act as drug carriers but will also disrupt the mucus layer and self-propel to their target site, thus overcoming the barrier. A comparative study will be performed to assess the treatment’s efficacy compared to the standard of care, and medical advice will be received from Dr. Élez (VHUH) to ensure the translation of the results to the clinic. We believe that using an all-in-one system will certainly enhance the delivery and efficacy of the active therapeutic compound, thus potentially improving current treatments.

Samuel Sánchez Ordóñez –  Institut de Bioenginyeria de Catalunya (IBEC)
PoC – 2023 PE8

Arthritis, a widespread inflammatory condition, affecting millions globally, necessitates urgent advancements in therapeutic approaches. Predominantly characterized by osteoarthritis (OA), this debilitating condition causes joint pain and stiffness, notably impacting the knee, hand, and hip joints. OA, a chronic degenerative disease, intensifies with age, imposing a significant economic burden on healthcare systems. The insufficiency of current treatments highlights the need for innovative therapies. Tissue engineering and regenerative medicine offer promising avenues, with platelet-rich plasma therapy (PRP) emerging as a forefront contender. PRP harnesses the regenerative potential of growth factors (GFs) to stimulate tissue repair processes, particularly in cartilage and bone cells. However, clinical application faces hurdles, notably the rapid degradation of GFs within the intricate synovial fluid (SF) environment, limiting their therapeutic efficacy and distribution. To overcome these challenges, scientists explore advanced drug delivery systems utilizing nanoparticles (NPs) as carriers. Although promising, passive NPs diffusion through viscous biological barriers, such as joint fluids, remains a significant obstacle. In response, OrthoBots introduces enzyme-powered NPs, termed nanobots, as active carriers of GFs within SF. By utilizing enzymatic propulsion, nanobots aim to enhance GF transport and distribution, facilitating targeted cartilage regeneration. This innovative approach holds transformative potential, potentially revolutionizing arthritis therapy by overcoming current limitations and offering more effective and personalized treatment strategies. Through systematic in vitro studies and in vivo proof-of-concept demonstrations, OrthoBots will pave the way for the next generation of arthritis therapeutics, addressing the unmet clinical needs and improving patient outcomes.

Samuel Sánchez Ordóñez –  Institut de Bioenginyeria de Catalunya (IBEC)
PoC – 2024

Antibodies have become major players in the pharmaceutical industry and were valued at 0.16 US billion in 2023. Traditionally, antibodies are obtained after immunisation of different animals and then produced in relevant cells for use in research, diagnostics and therapy. In recent years, there is a growing public opinion in Europe to ban the use of animals for biomedical research, and therefore there is an increasing pressure to move from animal produced antibodies to design and produce them in vitro. Antibody engineering has another important advantage, which is the possibility of targeting a precise epitope and not rely on serendipity as when injecting an animal with an antigen. In recent years, there have been significant advances in protein design based on the use of artificial intelligence and precise force fields. Despite this, the majority of the companies that work on antibody design combine rational engineering with massive proprietary screening methods, and so far, there are no reported cases of fully de novo design of an antibody with nM affinity against a defined epitope. Using an interleukin receptor as a case study, we have shown that we can indeed fully design de novo a nanobody that recognizes the target with nM affinity, using our proprietary protein design software FoldX and ModelX. Experts consulted to date indicate that the results obtained so far are truly impressive, prompting us to continue validating and optimising our process. Our proposal has two main objectives: First, to fully automate our pipeline that involves epitope selection, antibody framework selection and docking, backbone move and side chain search. Second, demonstrate that our optimised pipeline can design fully de novo nanobodies against a defined target in a fast and cost-effective way. Success in both objectives will open the way to fully de novo antibodies with desired properties, and position ourselves in the search for funding and spin-off incorporation.

Luis Serrano – Centre de Regulació Genòmica (CRG)
PoC- 2024