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

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 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

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

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

Climate change has revived the debate on growth-vs-environment which may intensify in coming years. This project studies to what extent concerns about economic growth, ranging from pro- to anti-growth, hamper social-political support for ambitious climate policy, and how this can be amended. Using surveys, experiments and interviews, it assesses whether beliefs about growth-vs-environment affect policy opinions of distinct stakeholders (voters, policymakers, journalists, etc.), and if this is moderated by preferences regarding instrument types, such as standards, taxes or subsidies. The project further tests the role of information by comparing the effect of distinct beyond-GDP metrics on views about growth vs climate policy. In addition, it studies how growth concerns relate to the design of pledges in the Paris Agreement, as these demarcate national climate policies.
Based on collected data and derived insights, the project then undertakes system-dynamics and agent-based modelling to study the co-dynamics of climate-policy design and support. This will create models of the “dynamic policy-support cycle” (DPSC), comprising policy design, economic and emission impacts, opinion dynamics (i.e. support/resistance), and policy adaptation. It involves comparing growth strategies and climate policies using distinct beyond-GDP metrics, and connecting this to stakeholder opinion dynamics.
Informed by the model results, in a third part the project explores whether an agrowth strategy, which is precautious towards both economic and climate risks, can increase support for ambitious climate policy. Given stakeholder diversity, we perform interviews to decide about tailored strategies in this respect. Similar proposals to agrowth, notably under the label of “post-growth”, will be examined as well. The ultimate aim is to learn about dynamic packages with climate-policy instruments and a/post-growth measures that culminate in majority support for ambitious climate policy.

Jeroen van den Bergh – Universitat Autònoma de Barcelona (UAB)
AdG 2022 – SH7

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, the Netherlands
• Philipp Homan, University of Zurich, Switzerland
• Brita Elvevåg, UiT The Arctic University of Norway in Tromsø, Norway

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

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

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)
PoC2- 2022 -3rd

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

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 – 2022-3rd

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

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

Aftermath – The aftermath of the East Asian war of 1592-1598

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)

MIRAGE –Independence and Quality of Mass Media in the Internet Age

The Internet was expected to make citizens considerably more informed and better able to hold politicians and powerful interests accountable. Many predicted it would also effectively complement traditional media and improve news reporting. These expectations have not been met. There is no evidence that citizens have become more informed; they have, however, become more ideologically polarized, possibly due to online media overexposing users to like-minded content.

At the same time, traditional media are struggling: competition from online platforms has slashed advertising revenues forcing newspapers to close or downsize. These changes risk undermining the quality of reporting and making media more vulnerable to capture by special interests. My project examines how the Internet has transformed the way news is produced and disseminated, both directly and through its influence on traditional media, and its ultimate effect on media independence and content quality.

To this end, I tackle three distinct but intertwined questions:

First, I study how lower advertising revenues affect newspapers’ organization and content quality by exploiting the staggered introduction of advertising platform Craigslist across the US.
Second, I examine how media dependence on advertisers influences news bias by testing the relationship between advertising spending by car manufacturers and coverage of car safety recalls in US newspapers.
Finally, I study how the dependence of media on banks affects coverage of financial issues; focusing on Europe’s sovereign debt crisis, I test whether newspapers linked to banks with higher exposure to risky debt endorsed different crisis-management measures. My results will shed light on the deep transformations the media industry is undergoing and their implications for the quality of democracy.

Ruben Durante – Universitat Pompeu Fabra (UPF)
StG2017 – Social Sciences & Humanitites (SH1)

RAINDROPS – Resilience and Adaptation in Drylands. Identifying past water management practices for drought-resistant crops

RAINDROPS will investigate cultivation practices that support human resilience and adaptation in drylands, by developing an innovative and reliable methodology for the identification of water management practices from archaeobotanical remains. Irrigation, river floods or permanent water sources are often deemed necessary for cultivation to be practised in drylands. However, there are modern examples that testify to the existence of successful rain-fed cultivation systems, even in hyper-arid environments.

Quantification of the extent of these practices in the past has the potential to dramatically change our understanding of human adaptation and agriculture. By establishing a protocol for the accurate identification of rain-fed cultivation, RAINDROPS will pave the way for the investigation of this practice in the past. Highly controlled data on phytolith ratios, and carbon, oxygen and silicon isotopes from macro- and micro-remains from experimental fields of finger millet [Eleusine coracana (L.) Gaertn.] and sorghum [Sorghum bicolor (L.) Moench] will be validated with ethnographic evidence before being applied to selected key archaeological case studies. RAINDROPS will advance research in: (a) archaeobotanical methodology; (b) resilience theory; (c) physiology of drought-resistant crops; and (d) TEK of cultivation systems in drylands. This will for the first time allow a thorough evaluation of the relative importance of different water management practices in dryland cultivation in the past, and their significance for human adaptation to arid environments. The experimental work on finger millet and sorghum, at present two of the most important dryland crops, will provide valuable information on cultivation practices and plant physiology that will also inform current research on improvements of drought-resistant species –thereby contributing to work on improving the livelihood for over two billion people currently at risk from arid or changing environmental conditions.

Carla Lancelotti – Universitat Pompeu Fabra (UPF)
StG2017 – Social Sciences & Humanities (SH6)

SUEE – Strategic Uncertainty in Economic Environments

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)

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)

ELECTRON4WATER – Three-dimensional nanoelectrochemical systems based on low-cost reduced graphene oxide: the next generation of water treatment systems

The ever-increasing environmental input of toxic chemicals is rapidly deteriorating the health of our ecosystems and, above all, jeopardizing human health. Overcoming the challenge of water pollution requires novel water treatment technologies that are sustainable, robust and energy efficient. ELECTRON4WATER proposes a pioneering, chemical-free water purification technology: a three-dimensional (3D) nanoelectrochemical system equipped with low-cost reduced graphene oxide (RGO)-based electrodes. Existing research on graphene-based electrodes has been focused on supercapacitor applications and synthesis of defect-free, superconductive graphene. I will, on the contrary, use the defective structure of RGO to induce the production of reactive oxygen species and enhance electrocatalytic degradation of pollutants. I will investigate for the first time the electrolysis reactions at 3D electrochemically polarized RGO-coated material, which offers high catalytic activity and high surface area available for electrolysis. This breakthrough approach in electrochemical reactor design is expected to greatly enhance the current efficiency and achieve complete removal of persistent contaminants and pathogens from water without using any chemicals, just by applying the current. Also, high capacitance of RGO-based material can enable further energy savings and allow using intermittent energy sources such as photovoltaic panels. These features make 3D nanoelectrochemical systems particularly interesting for distributed, small-scale applications.

This project will aim at:
i) designing the optimum RGO-based material for specific treatment goals,
ii) mechanistic understanding of (electro)catalysis and (electro)sorption of persistent pollutants at RGO and electrochemically polarized RGO,
iii) understanding the role of inorganic and organic matrix and recognizing potential process limitations, and
iv) developing tailored, adaptable solutions for the treatment of contaminated water.

Jelena Radjenović – Institut Català de Recerca de l’Aigua (ICRA)
StG2016 – Physical Sciences & Engineering (PE3)

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

HYPER-INSIGHT – Hypermutated tumors: insight into genome maintenance and cancer vulnerabilities provided by an extreme burden of somatic mutations

Mutations are the fuel of any evolutionary process, and this also applies to carcinogenesis. The advent of affordable DNA sequencing has enabled mutagenic processes in the human soma to be quantified genome-wide, revealing a striking occurrence of hypermutated tumors. They exhibit an extreme load of somatic changes, often harbouring hundreds of single-nucleotide variants and/or indels per megabase. The HYPER-INSIGHT project is organized into three objectives, which aim to take advantage of the unique opportunity provided by genome sequences of hypermutated and ultramutated tumors. In particular, this work planned in this project aims to further our knowledge on (i) the regional organization of the DNA replication and repair program in human cells, and the determinants thereof, (ii) the extent of selection which acts on somatic variants in various pathways or complexes and (iii) opportunities for selectively targeting DNA repair deficiencies that manifest as hypermutation. Methodologically, our work will employ a three-pronged approach. First, we will perform a multitude of rigorous statistical analyses that draw on the rich and still-expanding resources provided by cancer genomics consortia. Second, we will perform exome and genome sequencing, focusing on ultramutated tumors caused by specific defects in the DNA maintenance machinery. Third, the project involves conditional essentiality screens on cancer cell lines with hypermutant backgrounds. Their goal is to discover synthetic lethality relationships, useful for targeting hypermutating cells, while sparing healthy ones. In summary, one of the promises of cancer genome sequencing projects was to elucidate the mechanisms underlying mutational processes in the human soma, advancing our understanding of this important facet of cancer biology. We will work towards realizing this promise, thereby strengthening the EU’s position in the global scientific endeavour.

Fran Supek – Institut de Recerca Biomèdica (IRB Barcelona)
StG2017 – Life Sciences (LS2)

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)

CheSSTaG – Chemotactic Super-Selective Targeting of Gliomas

I propose here a research program aimed to the design a completely new platform for drug delivery. I will combine our existing repertoire of molecular engineering tools based around our established approach to design responsive nanoparticles known as Polymersomes to integrate new features using clinically safe and biodegradable components that will make them super-selective and chemotactic toward glucose gradients so to deliver large therapeutic payload into the central nervous systems and the brain in particular targeting cancer cells harbouring within the healthy. We will do so by engineering components using supramolecular interaction inspired by biological complexity equipping carriers with the ability to self-propelled as a function of glucose gradient. I will complement our proposed design with advanced biological characterisation associating functional information arising form the physiological barrier to structural parameters integrated into the final carrier design.

Giuseppe Battaglia – Institut de Bioenginnyeria de Catalunya (IBEC)
CoC2018 – (PE5) Physical Sciences & Engineering

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 – (PE2) Physical Sciences & Engineering

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)

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Maria Escudero –
CoG 2021 – Social Sciences & Humanities (SH6)

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Maria Escudero –
CoG 2021 – Social Sciences & Humanities (SH6)

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Maria Escudero –
CoG 2021 – Social Sciences & Humanities (SH6)

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Maria Escudero –
CoG 2021 – Social Sciences & Humanities (SH6)

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)

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)

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)

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)

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)

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)

LICCI – Local Indicators of Climate Change Impacts. The Contribution of Local Knowledge to Climate Change Research

In the quest to better understand local climate change impacts on physical, biological, and socioeconomic systems and how such impacts are locally perceived, scientists are challenged by the scarcity of grounded data, which has resulted in a call for exploring new data sources. People with a long history of interaction with the environment have developed complex knowledge systems that allow them to detect local impacts of climatic variability, but these insights are absent in climate change research and policy fora. I will bring insights from local knowledge to climate research by 1) providing data on local climate change impacts on physical (e.g., shrinking glaciers) and biological systems (e.g., phenological changes) and on perceptions of climate change impacts on socioeconomic systems (e.g., crop failure due to rainfall patterns change) and 2) testing hypotheses on the global spatial, socioeconomic and demographic distribution of local climate change impacts indicators. Research will last five years.

The first 18 months, Preparation, I will train a team who will develop and implement a data collection protocol and design a web-based platform where citizens can enter information on local climate change impacts indicators.

During the following two years, Data collection, we will train 40 external PhD students to collect project’s data in data-deficient regions and disseminate the platform.

During the last 18 months, Analysis, the core team will use spatial matching and multivariate analysis to test hypotheses related to the spatial, socioeconomic, and demographic distribution of local climate change impacts indicators. External PhD students will analyse local data. Dissemination will be transversal to the project. This project will fill theoretical and spatial gaps on climate change impacts research. It will also improve local capacity to respond to climate change impacts and help bridge epistemological differences between local and scientific knowledge systems.

www.licci.eu

Victoria Reyes-García – Universitat Autònoma de Barcelona  (UAB)
CoG2017 – Social Sciences & Humanities (SH2)

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

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

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)

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)

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Mar Albà – IMIM
AdG2021 – ?

LIPOMET – Dietary Influences on Metastasis: How, When, and Why

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

TRANSFORMER:  Structural transformations and phase transitions in real-time

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)

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Dan Brockington – Universitat Autònoma de Barcelona (UAB)
AdG2021 –

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)

eNANO – Free electrons as ultrafast nanoscale probes 

With eNANO I will introduce a disruptive approach toward controlling and understanding the dynamical response of material nanostructures, expanding nanoscience and nanotechnology in unprecedented directions. Specifically, I intend to inaugurate the field of free-electron nanoelectronics, whereby electrons evolving in the vacuum regions defined by nanostructures will be generated, guided, and sampled at the nanoscale, thus acting as probes to excite, detect, image, and spectrally resolve polaritonic modes (e.g., plasmons, optical phonons, and excitons) with atomic precision over sub-femtosecond timescales. I will exploit the wave nature of electrons, extending the principles of nanophotonics from photons to electrons, therefore gaining in spatial resolution (by relying on the large reduction in wavelength) and strength of interaction (mediated by Coulomb fields, which in contrast to photons render nonlinear interactions ubiquitous when using free electrons). I will develop the theoretical and computational tools required to investigate this unexplored scenario, covering a wide range of free-electron energies, their elastic interactions with the material atomic structures, and their inelastic coupling to nanoscale dynamical excitations. Equipped with these techniques, I will further address four challenges of major scientific interest:

(i) the fundamental limits to the space, time, and energy resolutions achievable with free electrons;
(ii) the foundations and feasibility of pump-probe spectral microscopy at the single-electron level;
(iii) the exploration of quantum-optics phenomena by means of free electrons; and
(iv) the unique perspectives and potential offered by vertically confined free-electrons in 2D crystals.

I will face these research frontiers by combining knowledge from different areas through a multidisciplinary theory group, in close collaboration with leading experimentalists, pursuing a radically new approach to study and control the nanoworld.

F. Javier García de Abajo – Institut de Ciències Fotòniques (ICFO)
AdG2017 –  Physical & Engineering Sciences (PE3)

NANO-MEMEC – Membrane-based nano-mechanobiology: Role of mechanical forces in remodelling the spatiotemporal nanoarchitecture of the plasma membrane

Through evolution, cells have developed the exquisite ability to sense, transduce and integrate mechanical and biochemical signals (i.e. mechanobiology) to generate appropriate responses. These key events are rooted at the molecular and nanoscale levels, a size regime difficult to access, hindering our progress towards mechanistic understanding of mechanobiology. Recent evidence from my Lab (and others) shows that the lateral nanoscale organisation of mechanosensitive membrane receptors and signalling molecules is crucial for cell function. Yet, current models of mechanosensing are based on force-induced molecular conformations, completely overlooking the chief role of mechanical forces on the nanoscale spatiotemporal organisation of the plasma membrane.
The GOAL of NANO-MEMEC is to provide mechanistic understanding on the role of mechanical stimuli in the spatiotemporal nanoarchitecture of adhesion signalling platforms at the cell membrane. To overcome the technical challenges of probing these processes at the relevant spatiotemporal scales, I will exploit cuttingedge biophysical tools exclusively developed in my Lab that combine super-resolution optical nanoscopy and single molecule dynamics in conjunction with simultaneous mechanical stimulation of living cells. Using this integrated approach, I will:

First: dissect mechanical and biochemical coupling of membrane mechanosensing at the nanoscale.
Second: visualise the coordinated recruitment of integrin-associated signalling proteins in response to force, i.e., mechanotransduction.
Third: test how force-induced spatiotemporal membrane remodelling influences the migratory capacity of immune cells, i.e., mechanoresponse.

NANO-MEMEC conveys a new fundamental concept to the field of mechanobiology: the roles of mechanical stimuli in the dynamic remodelling of membrane nanocompartments, modulating signal transduction and ultimately affecting cell response, opening new-fangled research avenues in the years to come.

Maria F. García Parajo – Institut de Ciències Fotòniques (ICFO)
AdG2017 –  Life Sciences (LS1)

RLeap – From Data-based to Model-based AI: Representation Learning for Planning

Two of the main research threads in AI revolve around the development of data-based learners capable of inferring behavior and functions from experience and data, and model-based solvers capable of tackling well-defined but intractable models like SAT, classical planning, and Bayesian networks. Learners, and in particular deep learners, have achieved considerable success but result in black boxes that do not have the flexibility, transparency, and generality of their model-based counterparts. Solvers, on the other hand, require models which are hard to build by hand. RLeap is aimed at achieving an integration of learners and solvers in the context of planning by addressing and solving the problem of learning first-order planning representations from raw perceptions alone without using any prior symbolic knowledge. The ability to construct first-order symbolic representations and using them for expressing, communicating, achieving, and recognizing goals is a main component of human intelligence and a fundamental, open research problem in AI. The success of RLeap requires the development of radically new ideas and methods that will build on those of a number of related areas that include planning, learning, knowledge representation, combinatorial optimization and SAT. The approach to be pursued is based on a clear separation between learning the symbolic representations themselves, that is cast as a combinatorial problem, and learning the interpretations of those representations, that is cast as a supervised learning problem from targets obtained from the first part. RLeap will address both problems, not just in the planning setting but in the generalized planning setting as well where plans are general strategies. The project can make a significant difference in how general, explainable, and trustworthy AI can be understood and achieved. The PI has made key contribution to the main themes of the project that make him uniquely qualified to carry it forward.

Héctor Geffner – Universitat Pompeu Fabra (UPF)
AdG 2019 – Physical Sciences and Engineering (PE6)

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)

APMPAL-HET – Asset Prices and Macro Policy when Agents Learn and are Heterogeneous

Based on the APMPAL (ERC) project we continue to develop the frameworks of internal rationality (IR) and optimal signal extraction (OSE). Under IR investors/consumers behave rationally given their subjective beliefs about prices, these beliefs are compatible with data. Under OSE the government has partial information, it knows how policy influences observed variables and signal extraction. We develop further the foundations of IR and OSE with an emphasis on heterogeneous agents. We study sovereign bond crisis and heterogeneity of beliefs in asset pricing models under IR, using survey data on expectations. Under IR the assets’ stochastic discount factor depends on the agents’ decision function and beliefs; this modifies some key asset pricing results. We extend OSE to models with state variables, forward-looking constraints and heterogeneity. Under IR agents’ prior beliefs determine the effects of a policy reform. If the government does not observe prior beliefs it has partial information, thus OSE should be used to analyse policy reforms under IR. If IR heterogeneous workers forecast their productivity either from their own wage or their neighbours’ in a network, low current wages discourage search and human capital accumulation, leading to low productivity. This can explain low development of a country or social exclusion of a group. Worker subsidies redistribute wealth and can increase productivity if they “teach” agents to exit a low-wage state. We build DSGE models under IR for prediction and policy analysis. We develop time-series tools for predicting macro and asset market variables, using information available to the analyst, and we introduce non-linearities and survey expectations using insights from models under IR. We study how IR and OSE change the view on macro policy issues such as tax smoothing, debt management, Taylor rule, level of inflation, fiscal/monetary policy coordination, factor taxation or redistribution.

Albert Marcet – Universitat Autònoma de Barcelona (UAB)
AdG2017 – Social Sciences & Humanities (SH1)

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

LUNG-BIOREPAIR – Engineering a lung bacteria to treat idiopatic lung fibrosis and other non-infectious lung diseases

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
AdG 2020 – LS9

LEIT – Lossless information for Emerging Information Technologies

In nanoelectronic circuits, interconnects use more energy than microprocessors, a situation clearly undesirable for e.g. autonomous Internet of Things applications based on charge and other information tokens. Overcoming this issue and minimising overall power consumption will be of paramount importance as we move towards Beyond-CMOS circuits. A novel approach is required. In LEIT I propose to investigate phonons as information carriers with typical ultralow energies of a fraction of a meV. As quanta of lattice vibrations, the high interactivity of phonons presents two key challenges: phonon-phonon scattering and losses in waveguides caused by interaction with e.g. lattice defects. I propose to overcome this by engineering phonon-phonon scattering in custom-designed phononic crystal-based structures moving towards narrow frequencies and non-interacting phonons at room temperature. These structures will exhibit a unique combination of features to allow phonon filtering, reflection and confinement, as well as transmission from one element (source) to another (modulator and waveguides), all of which will serve to direct and guide the phonon waves. Phonon losses will be minimised even eradicated by using topological phononic waveguides to transmit phonons over micrometre distances. The technological platforms will be made from silicon (Si) and Si-compatible materials, also incorporating transition metal dichalcogenides in order to reach the higher frequencies. In LEIT I will draw on my extensive experimental research on phonons in semiconductor nanostructures, Si membranes and phononic crystals to demonstrate the viability of acoustic phonons as low-energy information carriers. By doing so I will lay the scientific and technological foundations of a new phononics-based approach to information processing, offering a means of transmitting information that is extremely low-power and lossless, while also compact and integrable with Si-technologies.

Clivia Sotomayor – Institut Català de Nanociència i Nanotecnologia (ICN2)
AdG 2019 – Physical Sciences & Engineering (PE7)

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)

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

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)

Niek van Hulst – ICFO
AdG2021 – PE

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

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

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

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

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

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

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

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

IT4-TALL – Clinical translation of a novel CD1a-directed CAR for relapse/refractory cortical T-cell Acute Lymphoblastic Leukemia: feasibility, efficacy and safety

Immunotherapy has revolutionized cancer treatment over the last decade. Adoptive cell immunotherapy with T-cells genetically redirected to a tumor-specific antigen using a chimeric antigen receptor (CAR) has achieved impressive response rates in advanced B-cell acute lymphoblastic leukemia (B-ALL). CAR T-cell strategies beyond B-cell tumors are, however, hampered by expected toxicities, owing to the lack of bona fide therapeutic and safe antigens. Indeed, there are no immunotherapeutic therapies (including CAR T-cells) approved for T-cell malignancies (T-ALL or T-cell lymphomas), as the shared expression of target antigens between CAR T-cells and T-blasts induces CAR T-cell fratricide and T-cell aplasia, leading to fatal immunodeficiency. We recently identified the CD1a antigen as a safe target for CD1a+ cortical T-ALL (coT-ALL), a major subgroup of T-ALL, and we have developed a novel CD1a-specific CAR. Results generated from my previous ERC-funded work (INFANTLEUKEMIA nº646903 and IT4-BALL nº811220) have just been protected by a European Patent (EP19382104.8; CARTs for the treatment of CD1a+ cancer). Our intellectual property rights coupled to our internationally-endorsed top-tier scientific publication are a major strength of our proof-of-principle demonstration that CD1a-directed CAR T-cells constitute a unique immunotherapy approach for coT-ALL. We propose to consolidate final technical-biological improvements and GMP-grade manufacturing of our CD1a-directed CAR T-cells in compliance with the requirements of the Spanish Regulatory Agency of Medicines and Medical Devices for advanced adoptive cellular therapies (AEMPS). Data from this project will be added to the final Investigational Medicinal Product Dossier (IMPD) of the CARCD1a T-cells to be submitted to AEMPS for regulatory approval to launch a pan-European open Phase Ib clinical trial for relapse/refractory coT-ALL in early 2022, ensuring social and health value of this innovative immunotherapy.

Pablo Menéndez – Institut de Recerca contra la Leucèmia Josep Carreras (IJC)
PoC – 2021

GENETTA – Genomic Data-Fusion Platform for Omics-Driven Precision Medicine

This PoC project aims to pave the road to commercialize a comprehensive data analytics platform enabling data-driven biomedical innovation and precision medicine. The platform is specifically designed to efficiently fuse and mine heterogeneous omic data, including genomes, epigenomes, proteomes, metabolomes, patient clinical profiles, drugs and their chemical similarities, disease and other ontologies, and other relevant omic data. The goal of this development is to provide the most advanced software platform for fusion and analytics of numerous heterogeneous multi-scale omic data that takes advantage of novel non-negative matrix trifactorization (NMTF)-based and network mining algorithms, providing dramatic improvements in the number and type of fused data, quantity of data, computational efficiency and biomedical accuracy compared to the most advanced omic data analytics platforms currently existing. The main goal of the PoC is to close the gap between the research results of ERC Consolidator Grant, ICON-BIO, and the production of a commercial data analytics platform for the bio-pharmaceutical sector. In particular, the solution will target biopharma companies to embed the platform into their existing Data Science resources and enable effective and efficient application of the platform’s explainable AI methods (resulting from ICON-BIO) to optimize and guide their discovery processes. The result of this effort will be the achievement of a market-ready Data Analytics Platform.

Natasa Przulj – Barcelona Supercomputing Centre – Centre Nacional de Supercomputació (BSC-CNS)
PoC – 2020

ICCION – Indigenous Climate Change Impacts Observation Network

The Local Indicators of Climate Change Impacts project (771056-LICCI-ERC-2017-COG) explores the potential of Indigenous and local knowledge (ILK) to contribute to climate research, but only tangentially addresses the marginalized position faced by Indigenous Peoples and local communities (IPLC) to bring their knowledge and perspectives to climate change research and policy fora. This PoC will bring IPLC knowledge and perspectives to climate change research and policy fora by 1) engage with IPLC on the co-design of a digital Indigenous Climate Change Impacts Observation Network (ICCION) and 2) engaging with the Local Communities and Indigenous Peoples Platform (LCIPP) of the UNFCCC, which has the mandate to strengthen IPLC knowledge and efforts related to addressing and responding to climate change. ICCION holds social, political, and technological innovative potential. The creation of an Indigenous Climate Change Impacts Observation Network is an innovative response to the IPCC call for more ground level data, as it will bring expand the geographical and temporal coverage of data collection on local indicators of climate change impacts. Moreover, partnering with IPLC and international organizations constitutes an important social innovation, as these alliances might facilitate the process of establishing a continuous, iterative, and bidirectional dialogue that foster IPLC effective participation in climate change science-policy fora. Finally, ICCION innovates in developing technological solutions to address technical (i.e., low internet access) and social concerns (i.e., Indigenous data sovereignty) that are of particular relevance for IPLC, but which have often been neglected in other technological developments. The long-term establishment of the observation network proposed here will contribute to give IPLC a more relevant voice in global climate policy fora, not only by informing climate change impact research, but also making it more socially acceptable.

Victoria Reyes-García – Universitat Autòmona de Barcelona (UAB)
PoC – 2019

SENFIB – Novel senolytic drugs for the treatment of lung and kidney fibrosis

SENFIB aims to deliver new drugs for the treatment of fibrotic diseases. Nearly one quarter of the global population will be over the age of 65 by 2050. Populations over 65 suffer from multiple degenerative diseases including tissue fibrosis, estimated to account for upwards of 45% of all-cause mortality. Animal models have demonstrated that senescent cells are causative in many fibrotic diseases including lung (i.e. idiopathic pulmonary fibrosis, IPF), and chronic kidney disease (CKD). Senescent cells have experienced damage or stress and have permanently exited the cell cycle, yet remain viable and long-lived, generating a persistent, sterile inflammation. Selective elimination of senescent cells in animal models of IPF, CKD, and aging demonstrated improved organ function and viability. Senolytics, molecules that induce preferential killing of senescent cells while leaving healthy cells intact, have emerged as a promising approach for tackling age-associated diseases; this was named one of the “10 Breakthrough Technologies” of 2020 by the MIT Technology Review. Thus far, few senolytics have been identified; their mode of action is often unknown, some present serious toxicities, and none has yet been demonstrated to have therapeutic activity in clinical trials. We propose to launch a drug discovery program based on a prioritized novel genetic target for senolysis, which we have already validated as senolytic using a tool compound in an in vivo model of IPF. We will deliver a lead series of molecules with IPR that meet all typical drug requirements plus in vivo Proof-of-Concept data in different mouse models of IPF and CKD. The ultimate goal of this project is to develop candidates for translation into clinical use to ameliorate fibrotic diseases via the selective elimination of senescent cells.

Manuel Serrano – Institut de Recerca Biomèdica (IRB Barcelona)
PoC – 2020

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

SAFE-ON – Technology for Smart Antimicrobial Coatings

Infectious diseases are a rapidly growing threat to humanity. For instance, the current COVID-19 pandemic, caused by the virus SARS-CoV-2, has already killed over 4.5 million people since 2019 and is taking a devastating socioeconomic toll around the world. Similarly, nosocomial infections are among the major causes of death and increased morbidity, causing thousands of deaths every year in Europe. Recently, the use of antimicrobial coatings has garnered increasing interest as a simple prophylactic strategy to combat these infectious diseases. In this PoC project, we aim advancing a new patented antimicrobial coating technology called SAFE-ON, into the pre-commercial stage, with the aim of demonstrating its breakthrough innovation potential and approaching its arrival to market. The first part of this project encompasses optimization of SAFE-ON technology as highly efficient, smart antimicrobial coatings. This entails the preparation of two antimicrobial coatings based on commercial formulations used in catheters and door-handle covers (one based on hydrogels and the other, on silicone), and subsequent testing of their antimicrobial capacity. It also involves preparing the first two SAFE-ON prototypes: one coated catheter and one door-handle cover. The second part of SAFE-ON will be dedicated to intellectual property (IP) and market aspects needed for the pre-commercialization of this new technology for antimicrobial coatings. This study will include a freedom-to-operate analysis and a market study to identify the antimicrobial coating producers that could ultimately serve as manufacturing partners. In this project we will design, fabricate and evaluate two innovative prototypes incorporating our iodine delivery platform, with the aim to assess the commercial viability of with antimicrobial SAFE-ON coatings, accelerate their market entry and ultimately, commercialize and further develop antimicrobial coatings and other biocide products based on our technology.

Daniel Maspoch – Institut Català de Nanociència i Nanotecnologia (ICN2)
PoC – 2022

FAIRGLUCOSE – Affordable and sustainable self-powered GLUCOSE sensing system for a global FAIR diabetes management

FAIRGLUCOSE proposes a low cost, sustainable and self-powered standalone glucose sensing system that relies on the well-known oxidation process of glucose coming from finger prick blood and transfers it to a voltage readout through an innovative and extremely simple strategy. In this way, a measurement that typically requires a potentiostat with a microcontroller and a battery is performed here with a minimalistic and battery-less circuit that fits within the footprint of a commercial glucose strip. This allows for a reduction not only in device cost, but also in the generation of waste of electrical and electronic equipment (WEEE or e-waste), avoiding the cumulative effect of millions of tests and their corresponding batteries performed at remote sites away from adequate recycling infrastructures. In order to interpret the result, the strip can be integrated in a card format that translates voltage into level bars accounting for low, normal and high glucose indicators – a solution that would substitute urine strips – or into a more sophisticated but still low-cost card containing a NFC chip allowing the transferring of a numeric result into a cell phone. Both cards could be implemented with state-of-the art flexible electronics technologies and could be reused infinite times, as energy would always come from the sample. The first targeted market of FAIRGLUCOSE solutions is located in low and middle-income countries, where cost of current glucometers limits severely the self-monitoring of blood glucose among population. However, at mid-term it is likely that the sustainability and affordability of the approach displaces the current glucose players in some market niches of developed countries and generates new applications in the healthcare and agro-food arena. Thus, FAIRGLUCOSE aims to investigate the commercial feasibility of this disruptive approach and create an innovation roadmap that allows deploying the technology where it can make the most.

Neus Sabaté – Institut de Nicroelectrònica de Barcelona – Centre Nacional de Microelectrònica (CSIC -IMB-CNM)
PoC – 2022

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

TRANSIONICS – Solid-State Ionics Synaptic Transistors for Neuromorphic Computing

Neuromorphic computing will revolutionize artificial intelligence for applications such as autonomous driving, smart diagnosis or natural-language understanding by emulating the operation of efficient biological neural networks. The main challenge in this field is the substitution of conventional transistors for synaptic transistors able to learn in ways similar to a neural synapse, i.e. the development of multistate non-volatile transistors. However, currently existing synaptic transistors have been developed using electrolytes that are by nature unstable and difficult to integrate such as ionic liquids or proton conducting polymers. TRANSIONICS will deliver highly stable (non-volatile), silicon-compatible and scalable solid state synaptic transistors by exploiting the first-ever room temperature oxide-ionic electrolyte developed in the ERC CoG grant (ULTRASOFC) held by the PI. TRANSIONICS transistors are able to modulate its channel properties with external stimulus like real neurons by reducing/oxidizing a mixed ionic-electronic conductor unveiled at ULTRASOFC. Additionally, TRANSIONICS is compatible with mainstream microelectronics fabrication technology, which makes it ideal for developing high density brain-like computer chips. The goals of the TRANSIONICS project are i) to evaluate the technical feasibility for the fabrication of unique all-solid-oxide synaptic transistors with lateral architecture; ii) to assess the silicon- compatibility and scalability of the TRANSIONICS transistors; iii) to define an IPR strategy for technology transfer; iv) to build a value proposition for a startup company and to identify customer segments with industrial partners. To achieve these goals, the PI has joined around the project team that combines applied research, technology transfer and market uptake expertise.

Albert Tarancón – Institut de Recerca en Energia de Catalunya (IREC)
PoC1 – 2022