ERC Grants

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

Arnau Sebé-Pedrós – Centre de Regulació Genòmica (CRG)
CoG 2024 – LS8

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)

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)
AdG 2023 – Physical sciences & engineering (PE2 – Fundamental Constituents of Matter)

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)
AdG 2023 – Social sciences & humanities (SH6 – The Study of the Human Past)

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)

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

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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

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 

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

Aftermath seeks to understand the legacy of the East Asian War of 1592-1598. This conflict involved over 500,000 combatants from Japan, China, and Korea; up to 100,000 Korean civilians were abducted to Japan. The war caused momentous demographic upheaval and widespread destruction, but also had long-lasting cultural impact as a result of the removal to Japan of Korean technology and skilled labourers. The conflict and its aftermath bear striking parallels to events in East Asia during World War 2, and memories of the 16th century war remain deeply resonant in the region. However, the war and its immediate aftermath are also significant because they occurred at the juncture of periods often characterized as “medieval” and “early modern” in the East Asian case.

What were the implications for the social, economic, and cultural contours of early modern East Asia?
What can this conflict tell us about war “aftermath” across historical periods and about such periodization itself?

There is little Western scholarship on the war and few studies in any language cross linguistic, disciplinary, and national boundaries to achieve a regional perspective that reflects the interconnected history of East Asia. Aftermath will radically alter our understanding of the region’s history by providing the first analysis of the state of East Asia as a result of the war. The focus will be on the period up to the middle of the 17th century, but not precluding ongoing effects.

The team, with expertise covering Japan, Korea, and China, will investigate three themes: the movement of people and demographic change, the impact on the natural environment, and technological diffusion. The project will be the first large scale investigation to use Japanese, Korean, and Chinese sources to understand the war’s aftermath. It will broaden understandings of the early modern world, and push the boundaries of war legacy studies by exploring the meanings of “aftermath” in the early modern East Asian context.

Rebekah Clements – Universitat Autònoma de Barcelona (UAB)
StG2017 – Social Sciences & Humanitites (SH6 – Cultures & Cultural Production)

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 – Social sciences and humanities (SH5)

This proposal concerns two sets of projects that tackle theoretical challenges raised by the data broker and online advertisement industry. 1-Strategic Uncertainty (SU) in Economic Environments: By assuming that individuals have correct beliefs about others’ behavior, the equilibrium approach in economics assumes away SU. But SU is central to many settings. Testament to this is the existence of a data broker industry, in which data on agents’ behavior are traded: this information would have no value without SU. Within game theory, non-equilibrium concepts such as rationalizability and models of level-k reasoning have been developed to study SU. But these models have had a limited impact on broader economics. This is partly due to the weakness and limited tractability of these concepts.

Part 1 tackles SU in order to favor a better integration within economics. From a behavioral perspective, I propose axiomatic foundations that justify modeling individuals’ reasoning as stemming from a cost-benefit analysis, and investigate (theoretically and experimentally) how these ideas shed light on the occurrence of equilibrium coordination under SU, i.e. as the result of purely subjective reasoning. From a classical perspective, I develop uniqueness and monotone comparative statics results for non-equilibrium concepts, to favor a better integration of SU in standard economics. Applications include problems of information disclosure of strategic datasets and identification in models of social interactions.

2-Online Auctions with Digital Marketing Agencies (DMA): I study the role of DMA in the auctions used to sell advertisement space on the web. I analyze how collusive bidding can emerge from bid delegation to a common DMA and how this undermines both revenues and efficiency of the auctions used by key players in the industry such as Facebook, Google and Microsoft-Yahoo!. Implications and extensions include business, policy and economics methodology.

Antonio Penta – Universitat Pompeu Fabra (UPF)
StG2017 – Social Sciences & Humanitites (SH1 – Macroeconomics; monetary economics; economic growth, labour economics)

EXTREME – The Rise and Fall of Populism and Extremism

In the recent years in advanced democracies there has been a wave of electoral successes of populist politicians supporting extreme messages. Is populism caused by negative economic shocks? If so, what are the mechanisms? What explains heterogeneity in responses to such shocks? In this project, I will test empirically if personal experiences, information environment, and their interaction with aggregate economic shocks shape people’s political decisions.
The project consists of three parts.
First, I will study how personal employment histories, potentially affected by globalization and technological shocks, individual predispositions, and information environment influenced voting for Trump. I will use a unique database of more than 40 million resumes for the period 2010-2016, the largest available repository of resumes of job-seekers in the US, which was not previously used in academic research, and match it with zipcode-level economic and voting variables.
Second, I will study how negative social experiences during the formative years affect subsequent labor market outcomes, antisocial behavior, and the support of populist agenda. I will examine how corporal punishment in schools in UK affected subsequent educational attainment, employment, antisocial behavior, and voting for UKIP and Brexit. I will digitize archival records on regulations and practice of corporal punishment in different educational authorities in the UK during 1970-80s, combining it with contemporary outcomes.
Third, I will examine what makes people actively resist extremist regimes even when it is associated with high personal costs. I will study a historical example of resistance to Nazi regime in Germany during the WWII, which provides unique methodological opportunity to study determinants of resistance to extremism in a high stake environment. I will use a self-collected dataset on treason cases to measure resistance, combining it with data on bombing and exposure to foreign propaganda.

Maria Petrova – Universitat Pompeu Fabra (UPF)
StG2018 – Social Sciences & Humanitites (SH1)

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

MAPMODERN– Social Networks of the Past: Mapping Hispanic and Lusophone Literary Modernity, 1898-1959

Data mining and big data approaches are changing the ways in which we create knowledge, access information and preserve our cultural heritage. This research applies cutting-edge technology to analyse a neglected aspect of European and non-European social and cultural life of the 20th century: the impact of Hispanic and Lusophone literary networks and cultural mediators in international modernity between 1898 and 1959. The project pursues three central goals: 1) to retrieve the lost history of Iberoamerican mediators in modernist intercultural and multilingual networks and reappraise their role; 2) to narrow the knowledge divide in terms of access and production in the Iberoamerican field by generating and making freely available new and reliable data that addresses the lack of documented cultural heritage, and 3) to offer an innovative and reproducible model that can be applied across periods, languages, and disciplines to analyse cross-border phenomena, under-examined mediators and networks and overshadowed geographical scales in their relations to the wider world. These goals will be achieved by a twofold methodology: i) an open and collaborative research tool providing a data source for quantitative and qualitative analysis on Iberoamerican mediators, and ii) four subprojects on key cultural transformation processes distinctive of modern societies (the institutionalization of Iberoamerican cultures, the rise of translated literature in key Iberoamerican modernist journals, the position of Iberoamerican women in the cultural field, and the role of Iberoamerican mediators in new forms of mass media). By combining computational methods, cultural, literary history, translation, sociology, gender and media studies, I will lead an interdisciplinary team of 6 researchers that will fill the gap in modernist studies and will offer an original, reproducible and empirically tested method for studying social human interaction within a global, cultural and decentred approach

Diana Roig-Sanz –  Universitat Oberta de Catalunya (UOC)
StG2018 – Social Sciences & Humanities (SH5)

EllipticPDE – Regularity and singularities in elliptic PDE’s: beyond monotonicity formulas

One of the oldest and most important questions in PDE theory is that of regularity. A classical example is Hilbert’s XIXth problem (1900), solved by De Giorgi and Nash in 1956. During the second half of the XXth century, the regularity theory for elliptic and parabolic PDE’s experienced a huge development, and many fundamental questions were answered by Caffarelli, Nirenberg, Krylov, Evans, Nadirashvili, Friedman, and many others. Still, there are problems of crucial importance that remain open. The aim of this project is to go significantly beyond the state of the art in some of the most important open questions in this context. In particular, three key objectives of the project are the following. First, to introduce new techniques to obtain fine description of singularities in nonlinear elliptic PDE’s. Aside from its intrinsic interest, a good regularity theory for singular points is likely to provide insightful applications in other contexts. A second aim of the project is to establish generic regularity results for free boundaries and other PDE problems. The development of methods which would allow one to prove generic regularity results may be viewed as one of the greatest challenges not only for free boundary problems, but for PDE problems in general. Finally, the third main objective is to achieve a complete regularity theory for nonlinear elliptic PDE’s that does not rely on monotonicity formulas. These three objectives, while seemingly different, are in fact deeply interrelated.

Xavier Ros-Oton – Universitat de Barcelona (UB)
StG2018 – Physical Sciences & Engineering (PE1)

OPTNETSPACE – Optimal Transport Networks in Spatial Equilibrium

Every year, the world economy invests a large amount of resources to improve or develop transport infrastructure. How should these investments be allocated to maximize social welfare? In this proposal, I propose to develop and apply new methods to study optimal transport networks in general-equilibrium models of international trade, urban economics and economic geography. The methodology will build on recent work (Fajgelbaum and Schaal, 2017), in which my coauthor and I studied the network design problem in a general neoclassical trade framework. In the first project, I develop a new framework to analyze optimal infrastructure investment in an urban setting. The model features people commuting between residential areas and business districts as well as a choice over the mode of transportation. We plan to evaluate the framework to historical data about specific cities. In the second project, I propose and implement an new algorithm to compute optimal transport networks in the presence of increasing returns to transport, a likely prominent feature of real-world networks. The algorithm applies a branch-and-bound method in a series of geometric programming relaxations of the problem. In the third project, I study the dynamic evolution of actual transport networks using satellite data from the US, India and Mexico. In the spirit of Hsieh and Klenow (2007), I use the model to measure distortions in the placement of roads between rich and poor countries. In the fourth project, I study the inefficiencies and welfare losses associated with political economy frictions among governments and planning agencies. I use the model to identify inefficiencies and relate them to measures of institutions and political outcomes. In the final project, I propose a new explanation behind the Zipf’s law distribution of city sizes. I show that Zipf’s law may result from particular topological properties of optimal transport networks that allocate resources efficiently in space.

Edouard Schaal – Centre de Recerca en Economia Internacional (CREI)
StG2018 – Social Scieces & Humanities (SH1)

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

MiMus – Ioculator seu mimus. Performing Music and Poetry in medieval Iberia

What was the role played by courtly musicians and poets in fostering a performative dimension of cultural life in the late Middle Ages? How did this contribute to the social value of the poet and musician as an artist? In the late medieval period the Crown of Aragon was a political and cultural crossroads, a coveted destination for artists of various kinds who attended the refined court of the Catalan kings. Musicians and performing entertainers with skills in the verbal and non-verbal domains were among the most sought after. This project will review and expand the corpus of documentary evidence informing us about musical activity and performing artists at the court of Aragon in the late medieval period, with the aim to analyse what this tells us about similar activity at other European courts. Thus, it will examine the professional profiles, cultural backgrounds and networks of patronage behind the minstrels who thrived in the Catalan court between 1235 and 1435.

The main source of information will be the Archive of the Crown of Aragon in Barcelona and the Archive of Valencia. The project will also consider the debt of Catalan poetry to foreign musicians, with the aim to establish whether any intertextuality exists between Catalan poetry and the poetry produced in the regions adjacent to the territories of the Crown of Aragon that was specifically mediated by the presence of foreign musicians at the Catalan court.

Specific objectives of the project will be:
1) to establish whether the ideas of minstrelsy passed down to us by literature and scholarship fit the real profiles of minstrels provided by medieval documents;
2) to evaluate the impact, where appropriate, of contacts between religious and ethnic communities in the profession of minstrelsy in late medieval Iberia;
3) to assess the role of queenship in musical and poetic patronage;
4) to clarify the influence of foreign musical traditions on Catalan poetry.

Anna Alberni – Universitat de Barcelona (UB)
CoG2017 – Social Sciences & Humanities (SH5)

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)

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)

The traditional view is that species and their genomes evolve only by vertical descent, leading to evolutionary histories that can be represented by bifurcating lineages. However, modern evolutionary thinking recognizes processes of reticulate evolution, such as horizontal gene transfer or hybridization, which involve total or partial merging of genetic material from two diverged species. Today it is widely recognized that such events are rampant in prokaryotes, but a relevant role in eukaryotes has only recently been acknowledged. Unprecedented genomic and phylogenetic information, and recent work from others and us have shown that reticulate evolution in eukaryotes is more common and have more complex outcomes than previously thought. However, we still have a very limited understanding of what are the impacts at the genomic and evolutionary levels. To address this, I propose to combine innovative computational and experimental approaches. The first goal is to infer patterns of reticulate evolution across the eukaryotic tree, and relate this to current biological knowledge. The second goal is to trace the genomic aftermath of inter-species hybridization at the i) long-term, by analysing available genomes in selected eukaryotic taxa, ii) mid-term, by sequencing lineages of natural fungal hybrids, and iii) short-term, by using re-sequencing and experimental evolution in yeast. A particular focus is placed on elucidating the role of hybridization in the origin of whole genome duplications, and in facilitating the spread of horizontally transferred genes. Finally results from this and other projects will be integrated into emerging theoretical frameworks. Outcomes of this project will profoundly improve our understanding of reticular processes as drivers of eukaryotic genome evolution, and will impact other key aspects of evolutionary theory, ranging from the concept of orthology to the eukaryotic tree of life.

Toni Gabaldón – Barcelona Supercomputing Centre – Centre Nacional de Supercomputació (BSC-CNS)
CoG 2016 – Life Sciences (LS8 – Environmenta Biology, Ecology & Evolution)

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)

FRAGMENT – FRontiers in dust minerAloGical coMposition and its Effects upoN climaTe

Soil dust aerosols are mixtures of different minerals, whose relative abundances, particle size distribution (PSD), shape, surface topography and mixing state influence their effect upon climate. However, Earth System Models typically assume that dust aerosols have a globally uniform composition, neglecting the known regional variations in the mineralogy of the sources. The goal of FRAGMENT is to understand and constrain the global mineralogical composition of dust along with its effects upon climate. The representation of the global dust mineralogy is hindered by our limited knowledge of the global soil mineral content and our incomplete understanding of the emitted dust PSD in terms of its constituent minerals that results from the fragmentation of soil aggregates during wind erosion. The emitted PSD affects the duration of particle transport and thus each mineral’s global distribution, along with its specific effect upon climate. Coincident observations of the emitted dust and soil PSD are scarce and do not characterize the mineralogy. In addition, the existing theoretical paradigms disagree fundamentally on multiple aspects. We will contribute new fundamental understanding of the size-resolved mineralogy of dust at emission and its relationship with the parent soil, based on an unprecedented ensemble of measurement campaigns that have been designed to thoroughly test our theoretical hypotheses. To improve knowledge of the global soil mineral content, we will evaluate and use available remote hyperspectral imaging, which is unprecedented in the context of dust modelling. Our new methods will anticipate the coming innovation of retrieving soil mineralogy through high-quality spaceborne hyperspectral measurements. Finally, we will generate integrated and quantitative knowledge of the role of dust mineralogy in dust-radiation, dust-chemistry and dust-cloud interactions based on modeling experiments constrained with our theoretical innovations and field measurements.

Carlos Pérez García-Pando – Barcelona Supercomputing Centre – Centro Nacional de Supercomputación (BSC – CNS)
CoG2017 – Physical Sciences & Engineering (PE10)

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)

ICON-BIO – Integrated Connectedness for a New Representation of Biology

The aim of the project is to develop a comprehensive framework for generalizing network analytics and fusion paradigms of non-negative matrix factorization to medical data. Heterogeneous, interconnected, systems-level omics data are becoming increasingly available and important in precision medicine. We are seeking to better stratify and subtype patients into risk groups, discover new biomarkers for complex and rare diseases, personalize medical treatment based on genomics and exposures of an individual, and repurpose known drugs to different patient groups. Existing methodologies for dealing with these big data are limited and a paradigm shift is needed to achieve quantitatively and qualitatively better results. The project is motivated by the recent success of non-negative matrix tri-factorization (NMTF) based methods for fusion of heterogeneous data in biomedicine. Though these methods have been known for some time, the availability of large datasets, coupled with modern computational power and efficient optimization methods, allowed for creation and efficient training of complex models that can make a qualitative breakthrough. For example, NMTF has recently achieved unprecedented performance on exceptionally hard problems of simultaneously utilizing the wealth of diverse molecular and clinical data in precision medicine. However, research thus far has been limited to special variants of this problem and used only fixed point methods to address these exciting examples of hard non-convex high-dimensional non-linear optimization problems. The ambition of the project is to develop general data fusion methods, from mathematical models to efficient and scalable software implementation, and apply them to the domain of biomedical informatics. The project will lead to a paradigm shift in biomedical and computational understanding of data and diseases that will open up ways to solving some of the major bottlenecks in precision medicine and other domains.

Natasa Przulj – Barcelona Supercomputing Centre – Centre Nacional de Supercomputación (BSC-CNS)
CoG2017 – Physical Sciences & Engineering (PE6)

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 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

i-NANOSWARMS – Cooperative Intelligence in Swarms of Enzyme-Nanobots

Samuel Sánchez Ordóñez – Institut de Bioenginyeria de Catalunya (IBEC)
CoG2019 – Physical Sciences Engineeering (PE8)

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

We have recently identified metastasis-initiating cells (MICs) in several types of tumors (Nature, 2017)1. Intriguingly, MICs: (i) are exclusive in their ability to generate metastases when transplanted; (ii) express the fatty acid channel CD36 and have a unique lipid metabolic signature; (iii) are exquisitely sensitive to the levels of fat in circulation, thus providing a link between the predisposition of metastasis and dietary fat; (iv) are highly sensitive to CD36 inhibition, which almost completely abolishes their metastatic potential. We still do not know how MICs promote metastasis or how MICs are influenced by dietary fat. In particular: (A) where are MICs located within the tumor, and does this location influence their behavior? How and where do they attach and expand at metastatic sites? (B) Why are MICs so sensitive to specific dietary lipids, and how do these lipids promote metastasis at the molecular and cellular levels? (C) Is the prolonged consumption of a high-fat diet a risk factor for developing metastatic tumors? If so, what are the underlying genetic and epigenetic causes for this effect? Can we revert these causes? To answer these questions, we will combine state-of-the-art in vivo functional models of metastasis, with quantitative metabolomics and proteomics, epigenetic and geographical position (3D) single-cell transcriptomic studies, as well as integrative computational analyses, using preclinical models and patientderived carcinomas of melanoma, oral cancer and breast cancer. We expect our project to provide fundamental insights into the mechanisms of metastasis, and how they are influenced by diet. This is highly relevant as 1) large quantities of fatty acids are typically consumed in Western diets; and 2) metastasis is the leading cause of cancer-related deaths. We also tackle a timely medical unmet need by exploring the therapeutic anti-metastatic potential of targeting fatty acid metabolism in cancer patients.

Salvador Aznar-Benitah – Institut de Recerca Biomèdica (IRB Barcelona)
AdG2017 – Life Sciences (LS4)

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

Chemical and material sciences are key drivers of our modern economy with transformative impact at all levels of society. In particular, the ability to synthesize and to tailor substances and materials with specific function is all-pervading into modern society. Vital is a firm understanding of structural transformations of molecules and phase transitions of solids as they are omnipresent, e.g. as formation and breakage of molecular bonds, proton motion and isomerization, and as collective phenomena in phase transitions. Gaining insight into the ultrafast correlated dynamics is highly challenging and requires revolutionary methodologies and innovative approaches to capture the dynamics from its onset.

TRANSFORMER will provide unprecedented insight into the real-time electronic and nuclear dynamics of molecular transformations and phase transitions with advanced new methodologies and a multi-faceted approach to the investigation. The project exploits our pioneering achievements in attosecond soft X-ray spectroscopy (XAFS) and laser-induced electron diffraction (LIED) to pinpoint in real-time which electronic states participate at which nuclear configuration. The proposal consists of three objectives:

• We will establish the methodical boundaries of LIED for space-time imaging of isolated molecules.
• We will extract simultaneous and real-time electronic and nuclear information, thus gain insight into the underlying many-body quantum correlations.
• We will use our methodology to realize resolving both, molecular isomerization and a solid’s metal-to-insulator phase transition, in its electronic and nuclear degrees of freedom and in real time.

If successful, TRANSFORMER would undoubtedly provide an unprecedented view into electronic and nuclear dynamics, thereby reaching far beyond the state of the art with clear potential to surpass current limits in molecular and material sciences.

Jens Biegert –Institut de Ciències Fotòniques (ICFO)
AdG2017 – Physical Sciences Engineering (PE4)

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)

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)

NOQIA – NOvel Quantum simulators – connectIng Areas

Quantum simulators (QS) are experimental systems that allow mimic hard to simulate models of condensed matter, high energy physics and beyond. QS have various platforms: from ultracold atoms and ions to superconducting qubits. They constitute the important pillar of quantum technologies (QT), and promise future applications in chemistry, material science and optimization problems. Over the last decade, QS were particularly successful in mimicking topological effects in physics (TEP) and in developing accurate quantum validation/certification (QVC) methods. NOQIA is a theory project, aimed at introducing the established field of QS+TEP+QVC into two novel areas: physics of ultrafast phenomena and attoscience (AS) on one side, and quantum machine learning (ML) and neural networks (NN) on the other. This will open up new horizons/opportunities for research both in AS and in ML/NN. For instance, in AS we will address the question if intense laser physics may serve as a tool to detect topological effects in solid state and strongly correlated systems. We will study response of matter to laser pulses carrying topological signatures, to determine if they can induce topological effects in targets. We will design/analyze QS using trapped atoms to understand and detect TEP in the AS. On the ML/NN side, we will apply classical ML to analyze, design and control QS for topological systems, in order to understand and optimize them. Conversely, we will transfer many-body techniques to ML in order to analyze and possibly improve performance of classical machine learning. We will design and analyze quantum neural network devices that will employ topology in order to achieve robust quantum memory or information processing. We will design/study attractor neural networks with topological stationary states, or feed-forward networks with topological Floquet and time-crystal states. Both in AS and ML/NN, NOQIA will rely on quantum validation and certification protocols and techniques.

Maciej Lewenstein –Institut de Ciències Fotòniques (ICFO)
AdG2018 – Physical Sciences Engineering (PE2)

Albert Marcet – Centre de Recerca en Economia Internacional (CREI)
AdG2017 – Social Sciences & Humanities  (SH1 – Individuals, Markets & Organizations)

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

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

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)

The environment we live in is both complex and time varying. Examples of recent instabilities include the recent financial crises as well as the more recent COVID-19 pandemic and the war in Ukraine, which have substantially altered our world. Currently, however, the way researchers implement forecasts as well as the way they estimate the effects of economic policies is based on methods that either impose restrictive assumptions on the nature of instabilities or quickly become computationally demanding in the presence of instabilities.

This project proposes to develop a local projection-based estimator for time-varying parameter models and their impulse response functions in unstable environments, which we refer to as the “time-varying parameter local projection” estimator (or “TVP-LP” in short). The proposed estimator is expected to provide a feasible approach to conveniently and flexibly estimate economic models in unstable environments as well as, more broadly, forecasting and assessing the effects of economic policies. The proposed estimator can be generalized to include instrumental variables as well as be applied in vector autoregressive models with external instruments while being robust to the presence of instabilities. The proposed methodology is expected to have widespread applicability given the increasing interest in using convenient local projection estimators and the substantial evidence of instabilities in macroeconomic models.

In contrast to conventional time-varying parameter VAR models, the proposed time-varying parameter local projection estimator is robust to the presence of non-invertibility due to omitted variables and misspecification and its estimation is less computationally challenging.

The advantages of the methodology will be illustrated in terms of forecasting ability as well as the evaluation of the effects of economic policy (in particular, fiscal policy).

Barbara Rossi – Universitat Pompeu Fabra (UPF)
AdG 2022 – SH1

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

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 – Social Sciences & Humanitites (SH2)

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 & Analytical Chemical Sciences

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

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[1]growth policies through, and how can the public be engaged in them? What new scientific paradigm could answer such questions? Our 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[1]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 – Universitat Autònoma de Barcelona (UAB)
SyG 2022

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

BCLLatlas – Single-cell genomics to comprehensively understand healthy B-cell maturation and transformation to chronic lymphocytic leukemia

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.

Iñaki Martin-Subero – Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
SyG 2018 – SyG3LSb

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

Understanding the establishment of an animal body plan is an important challenge of modern biology. Progress has been mainly limited by (1) a separation of research fields studying genetic and biophysical mechanisms, and (2) a lack of approaches to mimic multicellular tissue organization from first principles. In a cross- disciplinary effort, we will focus on the earliest stages of animal development, when the first steps of cell differentiation define the primary body axis through spatial symmetry breaking, laying the foundation for the future body plan. Our goal is to identify the fundamental mechanisms controlling this symmetry breaking process. To this end, we will study the mechanisms that connect global tissue geometry (shape, size, dimension and physical boundary conditions) with mechano-chemical interactions at the single-cell level. We address the following questions: (i) How do global shape and size control local cellular states and interactions? (ii) How do local cellular states and interactions induce robust symmetry breaking at the tissue level? (iii) To what extent can geometry control cell fate specification in a species-independent manner? To overcome previous limitations, we will establish a comprehensive methodological toolbox of synthetic bottom-up approaches and functional ex vivo assays. We use embryonic stem cells from mouse, zebrafish, and ultimately human as model systems. This will be combined with advanced biophysical techniques and theoretical modeling to systematically dissect the mutual coupling between genetic patterning mechanisms and morphogenetic processes, thereby revealing the multicellular dance underlying tissue symmetry breaking. Our results will shed new light on the long-standing question of how complex biological forms are robustly built from a single fertilized egg, impacting our understanding of organism development and maintenance, and opening new directions for the controlled design of artificial tissues and organs.

Verena Ruprecht – Centre de Regulació Genòmica (CRG)
SyG 2022

BIOMECANET – Integration of the Biochemical and Mechanical Networks of Cell Division

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

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

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 (i.e., protein palmitoylation). Furthermore, our unpublished data indicates that blocking a specific protein involved in the lipidation machinery is sufficient to significantly reduce tumor growth and metastatic progression. Thus, targeting this particular lipid signaling machinery may represent an unexplored solution to combat metastasis. However, there is little information on this target regarding metastasis and no specific clinical-grade inhibitors are available. Using high-throughput screening (HTS) methods, PalmitoMET aims to identify novel molecules capable of inhibiting the activity of this enzyme 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)
PoC – 2023

We propose here the development of novel nanomedicines to identify anti-inflammatory therapies. We will optimise novel synthetic procedures to control polymer primary sequence, nanomedicine size, and degradation profiles to determine the formulations that target most selectively macrophages and have the most potent anti-inflammatory effect using high-content in vitro screening. We will follow these by appropriate in vivo testing using several models of inflammation in collaboration with specialised research groups. We plan to patent the methodology synthesis and possibly two or more new compounds that will be identified to protect intellectual property (IP). Alongside we will develop a business plan for product development, manufacturing, and commercialisation. Depending on the IP strategy, we envisage the establishment of a new venture either alone, via an appropriate investment campaign, or in collaboration with already established ventures that will bring the nanomedicine as close as possible to clinical evaluation.

Giuseppe Battaglia – Institut de Bioenginyeria de Catalunya (IBEC)
PoC – 2023

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

SWIRL – Short-wave Infrared Light emitters based on Colloidal Quantum Dot Technology

Optical sensing and imaging has evolved from taking digital images to a powerful metrology, imaging and data acquisition technique by expanding the spectral coverage from the visible to the short-wave infrared (SWIR). SWIR sensing and imaging is the cornerstone of advanced imaging techniques for 3D visualization, night vision, imaging though adverse weather conditions, biomedical imaging, spectroscopy for food quality and health monitoring, just to name a few. The huge market size of such applications, especially by entering volume markets including consumer electronics and automotive, has led to the first commercial appearances of low cost CMOS compatible SWIR photodetectors and image sensors. Yet for the realization of the afore-mentioned technologies the optical source is an equally important and crucial component to be considered at system level. To date, there is a lack of infrared optical sources that are CMOS compatible, low-cost with competitive performance over the standard costly epitaxial III-V light emitters. Moreover high cost and epitaxial growth manufacturing processes have limited the size and form factor of those sources to small and rigid elements preventing their use as high power and large area illumination sources. SWIRL will undertake this challenge to develop high performance low-cost SWIR optical sources with tunable emission peaks and spectral bandwidths across the eye-safety SWIR window, exploiting colloidal quantum dot technology. By leveraging engineering at the nanoscale and solution processed materials we will develop in TRL4/5 SWIR optical emitters that are low-cost, high efficiency, even rivalling their epitaxial counterparts, and spectrally versatile across the SWIR. We will further demonstrate their use in key applications related to automotive industry as optical sources for active SWIR imaging and in-cabin monitoring in the eye-safety infrared window.

Gerasimos Konstantatos – Institut de Ciències Fotòniques (ICFO)
PoC – 2022

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

Monitoring gases and particles through the use of smart sensors has a crucial role in a wide range of applications, from environmental control to breath analysis for diagnostics. With the information provided by these sensors, we are able to predict, prevent and act in potentially dangerous situations. In order for the data to be effectively transferred, the gas sensors must be integrated into portable devices with wireless connectivity, and must be miniaturized concurrently. To meet this requirement, the sensors must possess high sensitivity, selectivity, speed, ultra-low power consumption, and compatibility with silicon technology. However, currently no existing technology on the market fulfils all of these criteria. POLARSENSE aims out to develop an optical (infrared) gas sensor demonstrator chip based on a novel graphene electro-polaritonic platform that is designed to address all of the aforementioned technical and commercial requirements. This will be demonstrated through its functionality and performance, with the capability of detecting multiple gases in a scalable, CMOS compatible system with a sensitivity of 0.1 ppm, alongside specific optically active elements and an electrical detector all integrated within one single device. The result is a highly compact and efficient sensing platform that does not require an external photodetector. To achieve this, POLARSENSE will simulate, design, and fabricate a demonstrator chip in accordance with the specifications of our industrial partners, and test with a compact interferometer with a broadband infrared source to evaluate the performance.
We will then validate the sensing performance of the demonstrator system with acetone gas in a matrix containing different concentrations of ethanol and/or water vapor that are typically present in breath analyzer and environmental monitoring applications.

Frank Koppens – Institut de Ciències Fotòniques (ICFO)
PoC – 2023 – PE3 – Condensed Matter Physics

Anti-CD19 immunotherapies based on Bi-specific T-cell Engagers (BiTE) or chimeric antigen receptor (CAR)-expressing T-cells have revolutionized the treatment of refractory/relapse (R/R) B-cell acute lymphoblastic leukemia (B-ALL). However, despite initial impressive complete response (CR) rates, many patients relapse few months after anti-CD19 immunotherapy; in many cases with CD19 antigen loss. Such relapses are devastating, and patients are left with virtually no further treatment options. Dual targeting of the pan-B antigens CD19 and CD22 has been proposed as a therapeutic strategy to distribute the antigenic pressure over two molecules and to reduce immune escape by covering practically all B-ALL blast subclones. CD19/CD22-directed dual CARs have in fact been proposed to overcome B-ALL immunoediting during CAR T-cell therapy but, unfortunately CD19/CD22 dual CAR-treated R/R B-ALL patients showed CR rates not sustained over time and relapse with limited CAR T-cell expansion. In contrast to CAR T-cells, BiTEs-secreting T-cells represent a unique strategy capable of redirecting bystander T-cells to tumor cells because T-cell-produced BiTEs will be continuously secreted and will decorate, through the CD3scFv, the cell surface of practically all circulating and ex vivo manufactured bystander T-cells. Our overarching goal is to provide a novel and innovative T-cell redirecting immunotherapy for the treatment of R/R B-ALL by dual targeting both CD22 and CD19 with T-cells modified to simultaneously secrete CD22xCD3 BiTEs and express CD19 CAR (referred to BiTECAR). This strategy harnesses the biological advantages of both CARs and BiTEs while minimizing their limitations and will circumvent the potential low transduction efficiencies of the BiTECAR construct because the CD22-BiTE secreted by transduced T-cells will decorate the bystander (untransduced) T-cells boosting the durability and strength of T-cell responses.

Pablo Menéndez – Institut de Recerca contra la Leucèmia Josep Carreras (IJC)
PoC – 2022-2nd-2

Catalysts are able to reduce activation barriers of reactions making them possible at lower pressure an temperatures. Enzymes are the most efficient, specific, and selective catalysts known. Green chemistry has emerged as a new area focusing on use of environmentally friendly, non-hazardous and efficient solvents and catalysts in the synthesis of new products. Enzymes are non-toxic, and capable of operating under mild biological conditions, which makes them green catalysts offering an attractive alternative to traditional catalysis. However, their application in industry is rather limited as most industrial processes lack a natural enzyme. The solution is the routine design of enzymes, but this task has not yet been achieved due to several limitations, such as the high complexity of enzyme catalysis, the lack of accurate computational approaches for designing and estimating the catalytic potential of the new variants, and the inability to identify potential mutation sites far away from the active site of the enzyme. GREENZYME provides a new protocol able to capture this high complexity and design new enzymes capable of predicting active site and distal mutations, thus achieving high levels of activity (as it would occur in nature). This is achieved by integrating current Shortest Path Map-Ancestral Sequence Reconstruction (SPM-ASR)-based computational protocol developed in previous projects such as the ERC-StG NetMoDEzyme with deep learning techniques. Thanks to a well-thought-out exploitation and communication strategy, will make possible the premise of routine enzyme design. This will have a large-scale socio-economic impact, as it will reduce the production costs of many drugs and will allow industries to use environmentally friendly alternatives in line with new European policies.

Sílvia Osuna – Universitat de Girona (UdG)
PoC – 2022

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

Poly- and perfluoroalkyl substances (PFAS) have been used since the 1940s and are known as “forever chemicals” due to their extreme persistency to advanced (waste)water treatment strategies. Due to the strength of the C-F bond, each released molecule of PFAS remains in the environment. Today there are more than 9,000 known PFAS, majority of them being extremely resistant to any kind of degradation, and with high bioaccumulation potentials and toxicities.
Electrochemical processes can address the challenge of PFAS presence in water, provided that the anode material is low cost and can break the C-F bond without forming toxic byproducts. Graphene sponge anode developed by our team is the first material to fulfill both requirements. In this project, we will aim at upscaling the electrochemical treatment based on graphene sponge electrodes and testing its long-term performance in degrading PFAS from complex residual streams. This will enable us to answer key scientific and technical questions required for further technology adoption by the water industry, many of them related to the fundamental mechanisms of electrochemical C-F bond breakage and features of anodically polarized graphene. Based on the results achieved to date at lab-scale, GRAPHEC technology has a strong potential to evolve into a sustainable, chemical-free destruction technology for PFAS-laden wastewaters and achieve their complete destruction at ambient temperature and pressure, in modular units, with low capital and operational cost.
Finally, this project also aims at keeping the existing intellectual property and engaging early technology adopters in Europe and beyond to form a mature network of future clients and reach a technology readiness level (TRL) 6 at the end of the project. The project will deliver a new platform technology for the removal of toxic and persistent chemicals from water and is likely to play a key role in the EU´s Green Deal Agenda for securing a toxic-free environment.

Jelena Radjenovic –  Institut Català de Recerca de l’Aigua (ICRA)
PoC – 2022-3rd

Type 1 Diabetes (T1DM) results from autoimmune destruction of pancreatic insulin-producing -cells. Nowadays, insulin injections remain the leading therapeutic option. However, injection treatment fails to emulate the highly dynamic insulin release that -cells provide. During the last years, 3D cell-laden microspheres have been proposed as a major platform for bioengineering insulin-secreting constructs for tissue graft implantation and a model for in vitro drug screening platforms.
Current microsphere fabrication technologies have several drawbacks: the need for an oil phase containing surfactants, diameter inconsistency of the microspheres, and high time-consuming processes, among others. These technologies have widely used alginate for its rapid gelation, high processability, and low cost. However, its low biocompatible properties do not provide effective cell attachment. To overcome these limitations, Uniink proposes a high-throughput 3D bioprinting methodology that employs an ECM-like microenvironment for effective cell-laden microsphere production. Crosslinking the resulting microspheres with tannic acid (TA) prevents collagenase degradation and enhances spherical structural consistency while allowing the diffusion of nutrients and oxygen. In addition, the approach allows customization of microsphere diameter with extremely low variability. In conclusion, we will develop in Uniink a novel bio-printing procedure to fabricate large amounts of reproducible microspheres capable of secreting insulin in response to extracellular glucose stimuli. We expect that Uniink will represent a valid alternative to islet transplantation in T1DM patients, thus bringing cell therapy closer to the application in humans.

Javier Ramón-Azcón –  Institut de Bioenginyeria de Catalunya (IBEC)
PoC – 2022

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

Cytodesign – Novel engineered cytokines for human therapy

Cytokines are biomolecules of great potential interest for human therapy. They modulate the immune system and play an important role in cancer, inflammation, immune response and tissue regeneration. Despite their great potential, there are only a handful of cytokines approved for therapeutic purposes. This is because many of them can have adverse side effects as they usually target different cell types, which adds to their low serum half-life, high production costs, or lack of physiological efficacy. Different methods have been proposed to improve the pharmacodynamics and pharmacokinetics of selected cytokines. However, other properties do also need improvement, such as achieving effective local concentration at the target site; promoting the right activity in cytokines with dual functionality and decreasing toxicity by removing binding to unwanted cell types. To help solving these issues, we have developed a new protein design strategy that can be applied to all helix-bundle cytokines, many of which have been shown to be therapeutically relevant. The resulting products are uniquely modified cytokines with improved properties. Amongst such properties, our products show increase stability, higher affinity and specificity for their target receptors and should have reduced toxicity, all of which translate into greater safety and efficacy. We have initial evidence both (in vitro and in vivo) of the superiority of our designs over conventional cytokines, and in this project we will fully validate our technological platform and advance in the development of a business plan following the advice of several venture capital and pharma companies contacted to date, with the idea of laying the basis for the creation of a new start-up company.

Luis Serrano – Centre de Regulació Genòmica (CRG)
PoC2- 2022

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