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

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

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

GREENLULUS – Green Locally Unwanted Land Uses

This project examines the role played by the restoration and creation of environmental amenities in the redistribution of urban quality of life. Since no large-scale study has been conducted to measure if greener cities are less racially and socially equitable, I will analyze whether greening projects tend to increase environmental inequalities in 40 cities in the US and Europe and under which conditions such projects can address equity concerns. First, the study will a) develop a new method (an index) to quantify the racial and social impact of greening projects and to compare cities’ performance with each other; b) provide a spatial and quantitative analysis of neighborhood demographic, real estate, and environmental data; and c) apply the index methodology on a unique ranking of cities. Second, my research will analyze the response of private investors to the greening projects and identify the impact of new development projects proposed, approved, and implemented during or upon the completion of greening projects on the neighborhood socio-demographic characteristics. I will assess the extent to which development projects seem to encourage and/or accelerate gentrification, as such projects have been shown to be signs of residents’ exclusion. Additionally, this study will qualitatively analyze cases of community mobilization developed in response to new environmental amenities, through fieldwork in 16 critical neighborhoods (one neighborhood case per city) among the 40 cities. Last, this study will use qualitative methods to analyze the policies and measures that municipalities develop to address exclusion in “greening” neighborhoods. This groundbreaking longitudinal, systematic, in-depth, and large-scale project in the field of environmental justice will lead to a paradigm shift by hypothesizing that the social and racial inequities present in sustainability projects make green amenities Locally Unwanted Land Uses (LULUs) for poor residents and people of color.

Isabelle Anguelovski – Universitat Autònoma de Barcelona (UAB)
StG2015 – Social Sciences & Humanitites (SH3)

AMORE – A distributional MOdel of Reference to Entities

“When I asked my seven-year-old daughter “”Who is the boy in your class who was also new in school last year, like you?””, she instantly replied “”Daniel””, using the descriptive content in my utterance to identify an entity in the real world and refer to it. The ability to use language to refer to reality is crucial for humans, and yet it is very difficult to model. AMORE breaks new ground in Computational Linguistics, Linguistics, and Artificial Intelligence by developing a model of linguistic reference to entities implemented as a computational system that can learn its own representations from data.

This interdisciplinary project builds on two complementary semantic traditions:
1) Formal semantics, a symbolic approach that can delimit and track linguistic referents, but does not adequately match them with the descriptive content of linguistic expressions;
2) Distributional semantics, which can handle descriptive content but does not associate it to individuated referents.

AMORE synthesizes the two approaches into a unified, scalable model of reference that operates with individuated referents and links them to referential expressions characterized by rich descriptive content. The model is a distributed (neural network) version of a formal semantic framework that is furthermore able to integrate perceptual (visual) and linguistic information about entities. We test it extensively in referential tasks that require matching noun phrases (“the Medicine student”, “the white cat”) with entity representations extracted from text and images. AMORE advances our scientific understanding of language and its computational modeling, and contributes to the far-reaching debate between symbolic and distributed approaches to cognition with an integrative proposal. I am in a privileged position to carry out this integration, since I have contributed top research in both distributional and formal semantics. ”

Gemma Boleda – Universitat Pompeu Fabra (UPF)
StG2016 – Social Sciences & Humanitites (SH4)

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)

NetMoDEzyme – Network models for the computational design of proficient enzymes

Billions of years of evolution have made enzymes superb catalysts capable of accelerating reactions by several orders of magnitude. The underlying physical principles of their extraordinary catalytic power still remains highly debated, which makes the alteration of natural enzyme activities towards synthetically useful targets a tremendous challenge for modern chemical biology. The routine design of enzymes will, however, have large socio-economic benefits, as because of the enzymatic advantages the production costs of many drugs will be reduced and will allow industries to use environmentally friendly alternatives.

The goal of this project is to make the routine design of proficient enzymes possible. Current computational and experimental approaches are able to confer natural enzymes new functionalities but are economically unviable and the catalytic efficiencies lag far behind their natural counterparts. The groundbreaking nature of NetMoDEzyme relies on the application of network models to reduce the complexity of the enzyme design paradigm and completely reformulate previous computational design approaches. The new protocol proposed accurately characterizes the enzyme conformational dynamics and customizes the included mutations by exploiting the correlated movement of the enzyme active site residues with distal regions. The guidelines for mutation are withdrawn from the costly directed evolution experimental technique, and the most proficient enzymes are easily identified via chemoinformatic models. The new strategy will be applied to develop proficient enzymes for the synthesis of enantiomerically pure β-blocker drugs for treating cardiovascular problems at a reduced cost. The experimental assays of our computational predictions will finally elucidate the potential of this genuinely new approach for mimicking Nature’s rules of evolution.

Silvia Osuna – Universitat de Girona (UdG)
StG2015 – Physical Sciences & Engineering (PE4)

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)

microCrysFact – Microfluidic Crystal Factories (μ-CrysFact): a breakthrough approach for crystal engineering

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.

Josep Puigmartí – Universitat de Barcelona (UB)
StG2015 – Physical Sciences & Engineering (PE8)

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)

DAMOC – Diabetes Approach by Multi-Organ-on-a-Chip

Insulin secretion and insulin action are critical for normal glucose homeostasis. Defects in both of these processes lead to type 2 diabetes (T2D). Unravelling the mechanisms that lead to T2D is fundamental in the search of new molecular drugs to prevent and control this disease. Organ-on-a-chip devices offer new approaches for T2D disease modelling and drug discovery by providing biologically relevant models of tissues and organs in vitro integrated with biosensors. As such, organ-on-a-chip devices have the potential to revolutionize the pharmaceutical industry by enabling reliable and high predictive in vitro testing of drug candidates. The capability to miniaturize biosensor systems and advanced tissue fabrication procedures have enabled researchers to create multiple tissues on a chip with a high degree of control over experimental variables for high-content screening applications. The goal of this project is the fabrication of a biomimetic multi organ-on-a-chip integrated device composed of skeletal muscle and pancreatic islets for studying metabolism glucose diseases and for drug screening applications. Engineered muscle tissues and pancreatic islets are integrated with the technology to detect the glucose consumption, contraction induced glucose metabolism, insulin secretion and protein biomarker secretion of cells. We aim to design a novel therapeutic tool to test drugs with a multi organ-on-a-chip device. Such finding would improve drug test approaches and would provide for new therapies to prevent the loss of beta cell mass associated with T2D and defects in the glucose uptake in skeletal muscle.

Javier Ramón – Institut de Bioenginyeria de Catalunya (IBEC)
StG2016 – Physical Sciences & Engineering (PE8)

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)

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)

Tmol4TRANS – Efficient electronic transport at room temperature by T-shaped molecules in graphene based chemically modified three-terminal nanodevices

Tmol4TRANS aims to create operative molecular systems that will efficiently be inserted in three-terminal nanodevices to function as transistors at room temperature (RT). In the front-line of molecular electronics, the implementation of functional nanodevices in present technologies is mainly hampered by crucial unresolved issues like:
a) reliability of RT experiments on molecular transistors;
b) absence of controlled methodologies to deposit single molecules at specific sites;
c) low conductance values and
d) difficulties in achieving effective three-terminal devices (BJTs/FETs).

Such hindrances involve the nature of the molecules, the absence of controlled deposition methodologies at the nanoscale and the poor stability/contacts between molecules and electrodes. Stable two-terminal nanodevice based on few-layer graphene and containing a Curcuminoid molecule (CCMoid) that I made has shown reasonable molecular conductance at RT, where the CCMoid anchors to the electrodes by pi-pi stacking.

The specific goals of Tmol4TRANS are:
1) to synthesize multifunctional molecules base on “T-shaped” CCMoids and Porphyrin derivatives (PPDs) allowing efficient attachments to electrodes;
2) to fabricate chemically functionalized hybrid graphene transistors;
3) to establish a reliable methodology for positioning the molecules between the electrodes;
4) to investigate the conductance enhancement of the final systems, and
5) to provide the possibility of spin-dependent transport properties by binding such molecules to magnetic metals.

Here, the preparation of nanodevices involves feedback-controlled burning technique for the formation of the few-layer graphene electrodes (source/emitter and drain/collector) and the chemical functionalization of the gate/base, where T-shaped molecules will be fixed by click-chemistry. Tmol4TRANS would have a direct impact in Molecular Electronics and Spintronics, as well as in the broader scope of nanoelectronics.

Núria Aliaga – Institut de Ciència de Materials de Barcelona (CSIC-ICMAB)
CoC2016 – Physical Sciences & Engineering (PE5)

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)

RETVOLUTION – Reticulate evolution: patterns and impacts of non-vertical inheritance in eukaryotic genomes

The traditional view is that species and their genomes evolve only by vertical descent, leading to evolutionary histories that can be represented by bifurcating lineages. However, modern evolutionary thinking recognizes processes of reticulate evolution, such as horizontal gene transfer or hybridization, which involve total or partial merging of genetic material from two diverged species. Today it is widely recognized that such events are rampant in prokaryotes, but a relevant role in eukaryotes has only recently been acknowledged. Unprecedented genomic and phylogenetic information, and recent work from others and us have shown that reticulate evolution in eukaryotes is more common and have more complex outcomes than previously thought. However, we still have a very limited understanding of what are the impacts at the genomic and evolutionary levels.

To address this, I propose to combine innovative computational and experimental approaches. The first goal is to infer patterns of reticulate evolution across the eukaryotic tree, and relate this to current biological knowledge. The second goal is to trace the genomic aftermath of inter-species hybridization at the i) long-term, by analysing available genomes in selected eukaryotic taxa, ii) mid-term, by sequencing lineages of natural fungal hybrids, and iii) short-term, by using re-sequencing and experimental evolution in yeast. A particular focus is placed on elucidating the role of hybridization in the origin of whole genome duplications, and in facilitating the spread of horizontally transferred genes.

Finally results from this and other projects will be integrated into emerging theoretical frameworks. Outcomes of this project will profoundly improve our understanding of reticular processes as drivers of eukaryotic genome evolution, and will impact other key aspects of evolutionary theory, ranging from the concept of orthology to the eukaryotic tree of life.

Toni Gabaldón – Centre de Regulació Genómica (CRG)
CoG2016 – Life Sciences (LS8)

ITUL – Information Theory with Uncertain Laws

Shannon’s Information Theory paved the way for the information era by providing the mathematical foundations of digital information systems. A key underlying assumption of Shannon’s key results is that the probability law that governing system is known, allowing to optimize the codebook and decoder accordingly. There are a number of important situations where perfectly estimating the system law is impossible; in these situations the codebook and decoder must be designed without complete (or no) knowledge of the system law. The vast majority of the Information Theory literature makes strong simplifying assumptions on the model. Theoretical studies that provide a general treatment of information processing with uncertain laws are hence urgently needed. For general systems, standard asymptotic techniques cannot be invoked and new techniques must be sought. A fundamental understanding of the impact of uncertainty in general systems is crucial to harvesting the potential gains in practice. This project is aimed at contributing towards the ambitious goal of providing a unified framework for the study of Information Theory with uncertain laws. A general framework based on hypothesis testing will be developed and code designs and constructions that naturally follow from the hypothesis testing formulation will be derived. This unconventional and challenging treatment of Information Theory will advance the area and will contribute to Information Sciences and Systems disciplines where Information Theory is relevant. A comprehensive study of the fundamental limits and optimal code design with law uncertainty for general models will represent a major step forward in the field, with the potential to provide new tools and techniques to solve open problems in close disciplines. Therefore, the outcomes of this project will not only benefit communications, but also areas such as probability theory, statistics, physics, computer science and economics.

Albert Guillén – Universitat Pompeu Fabra (UPF)
CoG2016 – Physical Sciences & Engineering (PE7)

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)

HEINSOL – Hierarchically Engineered Inorganic Nanomaterials from the atomic to supra-nanocrystalline level as a novel platform for SOLution Processed SOLar cells

Solution processed inorganic nanocrystal (NC) materials have received enormous attention as an emerging technology to address the TW challenge in solar cells. These nanomaterials offer a unique opportunity for low-cost high efficiency all-inorganic solar cells. Despite the great efforts though, only a limited number of colloidal NC compounds has been successfully employed, which either rely on costly and scarce elements or toxic materials. HEINSOL´s mission is to develop the first highly efficient, robust solution processed solar cell platform based on environmentally friendly, Earth abundant materials.

To achieve this, HEINSOL undertakes a hierarchical approach to tailor the opto-electronic properties of inorganic NCs, starting from the control of composition and their properties at the atomic level and following up with further tailoring their optoelectronic properties via interactions at the supra-nanocrystalline level. HEINSOL, at the atomic level, will develop novel doping schemes for colloidal NCs to tailor their electronic character as well as passivation schemes to reduce the density of unfavourable trap states. At the supra-nanocrystalline level, HEINSOL will explore novel nano-heterojunctions that cater for efficient charge separation and suppressed recombination, elements of paramount importance in high performance solar cells. The microscopic properties of the NCs will be correlated with the macroscopic properties of the NC composites in operating devices, a methodology that will provide new insights on the underlying mechanisms at the nanoscale that govern the properties of those devices. The final goal is to introduce a new architectural platform for solution processed solar cells that will truly expand the material availability for the Photovoltaic Industry.

Gerasimos Konstantatos – Institut de Ciències Fotòniques (ICFO)
CoG2016 – Physical Sciences & Engineering (PE8)

TOPONANOP – Topological nano-photonics

One of the most fascinating phenomena in nature is the interplay between quantum mechanics and the flow of electrons in solids. A tangible example is the quantum hall effect, where electrons flow with virtually zero dissipation. That is because electrons can flow only in one direction, which makes them move around objects without scattering, representing robustness by topological protection. Essential for this effect is the magnetic field that breaks time-reversal symmetry. Recently, however, with the advent of novel exotic quantum materials, completely new concepts for topological and non-reciprocal phenomena have appeared on the horizon, without the need to apply any magnetic field. These materials exhibit intrinsic topological character due to quantum mechanical interferences.

TOPONANOP’s vision is to exploit these extraordinary quantum properties in order to control light at the nanoscale in a radically new way. One of the main objectives is to generate nanoscale optical fields (plasmons) that propagate in only one direction and implement topologically protected plasmons such that they move around defects and corners. At the same time, visualizing and controlling electromagnetic excitations will be used as a tool to unravel extraordinary phenomena in exotic quantum materials. To this end, TOPONANOP will apply novel low-temperature, THz and infrared, near-field imaging and spectroscopy techniques to directly spatially visualize the plasmon non-reciprocity and topological character. Topological nano-photonics is a new paradigm for novel quantum materials and will enable novel future applications in miniaturized photonic isolators, diodes and logic circuits and could lead to completely new concepts for communication systems, optical transistors and optical information processing.

Frank Koppens – Institut de Ciències Fotòniques (ICFO)
CoG2016 – Physical Sciences & Engineering (PE3)

NONCODRIVERS – Finding noncoding cancer drivers

Finding the mutations, genes and pathways directly involved in cancer is of paramount importance to understand the mechanisms of tumour development and devise therapeutic strategies to overcome the disease. Due to their role in cancer development and maintenance, the proteins encoded by cancer genes are candidate therapeutic targets. Indeed, in recent years we have witnessed the development of successful cancer-targeting therapies to counteract the effect of driver mutations. Although the coding part of the human genome has now largely been explored in the search for cancer driver mutations in most frequent cancer types, the extent of involvement of noncoding mutations in cancer development remains a mystery.

The main challenges faced are:

1) the functional role of most noncoding regions is unknown, and
2) tumours often have thousands of somatic mutations, so that distinguishing cancer driver mutations from bystanders is like finding the proverbial needle in a haystack.

To overcome these two challenges I propose to analyse the pattern of somatic mutations across thousands of tumours in noncoding regions to identify signals of positive selection. These signals are an indication that mutations in the region have been positively selected during tumour evolution and are thus directly involved in the tumour phenotype. The large scale analysis proposed here will allow us to create a catalogue of noncoding elements involved in different types of cancer upon mutations. We will study in detail a selected set of driver elements to uncover their specific function and role in the tumourigenic process. Furthermore, we will explore possibilities of counteracting their driver effect with targeted drugs. The results of this project may boost our understanding of the biological role of noncoding regions, help to unravel novel molecular causes of cancer and provide novel targeted therapeutic opportunities for cancer patients.

Núria López-Bigas – Institut de Recerca Biomèdica (IRB Barcelona)
CoG2015 – Life Sciences (LS2)

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)

CATA-LUX – Light-Driven Asymmetric Organocatalysis

Visible light photocatalysis and metal-free organocatalytic processes are powerful strategies of modern chemical research with extraordinary potential for the sustainable preparation of organic molecules. However, these environmentally respectful approaches have to date remained largely unrelated. The proposed research seeks to merge these fields of molecule activation to redefine their synthetic potential. Light-driven processes considerably enrich the modern synthetic repertoire, offering a potent way to build complex organic frameworks. In contrast, it is extremely challenging to develop asymmetric catalytic photoreactions that can create chiral molecules with a well-defined three-dimensional arrangement. By developing innovative methodologies to effectively address this issue, I will provide a novel reactivity framework for conceiving light-driven enantioselective organocatalytic processes. I will translate the effective tools governing the success of ground state asymmetric organocatalysis into the realm of photochemical reactivity, exploiting the potential of key organocatalytic intermediates to directly participate in the photoexcitation of substrates. At the same time, the chiral organocatalyst will ensure effective stereochemical control. This single catalyst system, where stereoinduction and photoactivation merge in a sole organocatalyst, will serve for developing novel enantioselective photoreactions. In a complementary dual catalytic approach, the synergistic activities of an organocatalyst and a metal-free photosensitiser will combine to realise asymmetric variants of venerable photochemical processes, which have never before succumbed to a stereocontrolled approach. This proposal challenges the current perception that photochemistry is too unselective to parallel the impressive levels of efficiency reached by the asymmetric catalysis of thermal reactions, expanding the way chemists think about making chiral molecules.

Paolo Melchiorre – Institut Català d’Investigació Química (ICIQ)
CoG2015 – Physical Sciences & Engineering (PE5)

INFANTLEUKEMIA – Genomic, Cellular and Developmental Reconstruction fo Infant MLL-AF4+ Acute Lymphoblastic Leukemia

Infant cancer is very distinct to adult cancer and it is progressively seen as a developmental disease. An intriguing infant cancer is the t(4;11) acute lymphoblastic leukemia (ALL) characterized by the hallmark rearrangement MLL-AF4 (MA4), and associated with dismal prognosis. The 100% concordance in twins and its prenatal onset suggest an extremely rapid disease progression. Many key issues remain elusive:
Is MA4 leukemogenic? Which are other relevant oncogenic drivers?
Which is the nature of the cell transformed by MA4?
Which is the leukemia-initiating cell (LIC)?
Does this ALL follow a hierarchical or stochastic cancer model?
How to explain therapy resistance and CNS involvement?
To what extent do genetics vs epigenetics contribute this ALL?

These questions remain a challenge due to:
1) the absence of prospective studies on diagnostic/remission-matched samples,
2) the lack of models which faithfully reproduce the disease and
3) a surprising genomic stability of this ALL.

I hypothesize that a Multilayer-Omics to function approach in patient blasts and early human hematopoietic stem/progenitor cells (HSPC) is required to fully scrutinize the biology underlying this life-threatening leukemia.

I will perform genome-wide studies on the mutational landscape, DNA and H3K79 methylation profiles, and transcriptome on a uniquely available, large cohort of diagnostic/remission-matched samples. Omics data integration will provide unprecedented information about oncogenic drivers which must be analyzed in ground-breaking functional assays using patient blasts and early HSPCs carrying a CRISPR/Cas9-mediated locus/allele-specific t(4;11). Serial xenografts combined with exome-seq in paired diagnostic samples and xenografts will identify the LIC and determine whether variegated genetics may underlie clonal functional heterogeneity. This project will provide a precise understanding and a disease model for MA4+ ALL, offering a platform for new treatment strategies.

Pablo Menéndez – Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
CoG2014 – Life Sciences (LS4)

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)

Family Justice – Justice and the Family: An Analysis of the Normative Significance of Procreation and Parenthood in a Just Society

This project examines the normative significance of procreation and parenthood for theories of justice. Important questions of justice about the family arise once we acknowledge and keep in view that procreation and parenthood are both integral to the existence of any society (and therefore, a just society), and that they involve substantial benefits and burdens for parents, children, and society at large. Yet existing theories of justice generally neglect these questions by assuming that the principles they formulate are to regulate the main institutions of societies constituted by fully formed adult individuals whose creation and care are taken as given.

The project identifies and analyses three main sets of questions about family justice:
1) Does justice require that parents and non-parents share, and share equally, the costs and benefits of having children, and how do different answers to this question bear on our theory of distributive justice?
2) What are the claims of justice that we have as children, how do they relate to those we have as adults, and who bears the correlative duties?
3) Do all contemporaries, regardless of whether they are parents or non-parents, have the same obligations of justice towards future generations, and how, if at all, are the justification and the content of those obligations affected by considerations about what parents owe their children and parents and non-parents owe to each other?

Addressing these questions contributes to developing normative-theoretical framework needed to address pressing public policy concerns, and also turns out to be more central to the formulation of a complete and defensible theory of justice than political philosophers have realised to date.

Serena Olsaretti – Universitat Pompeu Fabra (UPF)
CoG2014 – Social Sciences & Humanities (SH2)

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)

PERSISTDEBT – Debt and Persistence of Financial Shocks

In 2007 the US and Europe were overwhelmed by a banking crisis, which was followed by a severe economic recession. Historical studies show that financial crises are followed by periods of substantially stronger contraction of aggregate output and employment than non-financial recessions. Those studies also point out that the best predictor of financial crises is an ex-ante strong credit boom which, after the beginning of the crisis, followed by negative overall credit growth. Lastly, financial crises take a long time until recovering the pre-crisis levels.

– Why are the effects of credit shocks so strong and persistent over time?
– Is this effect explained by costly household deleveraging?
– What is the effect of household debt on consumption, savings and employment?
– Are there any benefits of debt in crises?
– Do some effects of the financial crisis work through a reduction in credit supply to firms and projects with high innovative content and productivity (high overall return, but with high credit and liquidity risk for the lenders)?
– Or are the cleansing effects in financial crises concentrated on the less productive firms?
– Can macroprudential policies based on strict control of loan-to-value ratios stop the building up of excessive household debt?

We plan to construct several new datasets to study these issues by merging information from different sources. For some issues, like the analysis of the effect of household debt on consumption and employment, we can take advantage of a natural experiment of randomized allocation of debt among individuals derived from the use of lotteries to allocate the rights to buy housing in Spain. In comparison to the existing literature, we can exploit the exogenous variation generated by these lotteries and some other combination of data (including exhaustive credit data) to obtain causal evidence and quantification on the interaction between debt, systemic risk, crises, and the new macroprudential policy.

José Luis Peydró – Universitat Pompeu Fabra (UPF)
CoG2014 – Social Sciences & Humanities (SH1)

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)

SUPERCELL – Single-Use paPER-based fuel CELLs

The advances in paper microfluidics taking place in recent years show that the new generation of paper-based devices will be able to overcome the limitations of traditional lateral flow tests and offer more accurate and specific information. However, the quantification of paper devices signals by colorimetry, electrochemistry or fluorescence entails the use of sensors and electronic components that require energy to function. Up to now, this has been solved by the use of battery-powered bulky readers, but this is only cost-effective when the reader is meant to be used thousands of times (hospital, care rooms, etc). It is becoming clear that the proliferation of paper-based sensors and their enormous potential impact when applied to personalized healthcare ask for innovative solutions that provide affordable readout. Despite dedicated on-chip solutions that integrate all the required components within a disposable test seem to be the most promising approach, available examples of realization are still scarce.

The SUPERCELL project aims to develop a new generation of disposable and low environmental impact fuel cells. The approach presented in this proposal will be a major breakthrough in the fuel cell field, as these devices are conceived for the first time as single-use and disposable power sources. It will also have an enormous impact in the point-of-care diagnostics domain, as it will provide simple, reliable and clean power sources to an upcoming generation of smart paper-based sensors and allow them to be energetically autonomous. Fuel will be harvested from the biological sample to be analyzed – in case of urine and blood – or taken from hydrogen produced in situ upon the addition of any liquid in the paper platform. The proposal is very innovative in conception as well as in technology as these devices will be developed by means of a smart integration of paper microfluidics, printed electronics and electrocatalysis technologies.

Neus Sabaté – Institute of Microelectronics of Barcelona (CSIC – IMB-CNM)
CoG2014 – Physical Sciences & Engineering (PE8)

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

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

MULTIFLEXO – Hierarchical multiscale modeling of flexoelectricity and related materials properties from first principles

Flexoelectricity, the coupling between an inhomogeneous deformation and the electrical polarization, has emerged a “hot” topic in modern materials science due to its cross-cutting relevance to many phenomena of fundamental and technological interest. Understanding the intriguing physics that governs its behaviour at the nanoscale is crucial to harnessing the potential of strain gradients in practical applications, and such a progress requires a substantial support from theory. In spite of impressive recent advances, first-principles calculations of flexoelectricity remain technically challenging at several levels: first, the breakdown of translational lattice periodicity that a strain gradient entails is problematic to treat in the context of traditional electronic-structure methods; second, the stringent length- and time-scale constraints of direct quantum-mechanical approaches limit the applicability of these methods to real problems, which often involve complex sample shapes and morphologies.

This project is aimed at overcoming these obstacles from their very root, via the development of ground-breaking innovations in electronic-structure and multiscale methodologies, and at using these advances to address a number of pressing physical questions in the context of energy and information technologies. In particular, the objectives of this project are:

(i) identifying the microscopic mechanisms that are most effective at delivering a strong flexoelectric response in a variety of materials;
(ii) understanding how these bulk effects are modified by size, shape and boundary conditions, and how they interact with other material properties;
(iii) supporting the experimental interpretation by critically assessing alternative physical interpretations of the observed effects (e.g. compositional gradients);
(iv) exploring the functionalities enabled by strain gradients in complex materials systems, including 2D crystals, semiconductor nanowires and multiferroics.

Max Stengel – Institut de Ciència de Materials de Barcelona (CSIC-ICMAB)
CoG2016 – Physical Sciences & Engineering (PE3)

ULTRA-SOFC – Breaking the temperature limits of Solid Oxide Fuel Cells: Towards a newfamily of ultra-thin portable power sources

Solid Oxide Fuel Cells (SOFCs) are one of the most efficient and fuel flexible power generators. However, a great limitation on their applicability arises from temperature restrictions. Operation approaching room temperature (RT) is forbidden by the limited performance of known electrolytes and cathodes while typical high temperatures (HT) avoid their implementation in portable applications where quick start ups with low energy consumption are required. The ULTRASOFC project aims breaking these historical limits by taking advantage of the tremendous opportunities arising from novel fields in the domain of the nanoscale (nanoionics or nano photochemistry) and recent advances in the marriage between micro and nanotechnologies. From the required interdisciplinary approach, the ULTRASOFC project addresses materials challenges to (i) reduce the operation to RT and (ii) technological gaps to develop ultra-low-thermal mass structures able to reach high T with extremely low consumption and immediate start up. A unique μSOFC technology fully integrated in ultrathin silicon will be developed to allow operation with hydrogen at room temperature and based on hydrocarbons at high temperature. Stacking these μSOFCs will bring a new family of ultrathin power sources able to provide 100 mW at RT and 5W at high T in a size of a one-cent coin. A stand-alone device fuelled with methane at HT will be fabricated in the size of a dice. Apart from breaking the state-of-the-art of power portable generation, the ULTRASOFC project will cover the gap of knowledge existing for the migration of high T electrochemical devices to room temperature and MEMS to high T. Therefore, one should expect that ULTRASOFC will open up new horizons and opportunities for research in adjacent fields like electrochemical transducers or chemical sensors. Furthermore, new technological perspectives of integration of unconventional materials will allow exploring unknown devices and practical applications.

Alberto Tarancón – Institut de Recerca de l’Energia de Catalunya (IREC)
CoG2015 – Physical Sciences and Engineering (PE8)

BePreSysE – Beyond Precision Cosmology: dealing with Systematic Errors

Over the past 20 years cosmology has made the transition to a precision science: the standard cosmological model has been established and its parameters are now measured with unprecedented precision. But precision is not enough: accuracy is also crucial. Accuracy accounts for systematic errors which can be both on the observational and on the theory/modelling side (and everywhere in between). While there is a well-defined and developed framework for treating statistical errors, there is no established approach for systematic errors. The next decade will see the era of large surveys; a large coordinated effort of the scientific community in the field is on-going to map the cosmos producing an exponentially growing amount of data. This will shrink the statistical errors, making mitigation and control of systematics of the utmost importance. While there are isolated and targeted efforts to quantify systematic errors and propagate them through all the way to the final results, there is no well-established, self-consistent methodology. To go beyond precision cosmology and reap the benefits of the forthcoming observational program, a systematic approach to systematics is needed. Systematics should be interpreted in the most general sense as shifts between the recovered measured values and true values of physical quantities. I propose to develop a comprehensive approach to tackle systematic errors with the goal to uncover and quantify otherwise unknown differences between the interpretation of a measurement and reality. This will require to fully develop, combine and systematize all approaches proposed so far (many pioneered by the PI), develop new ones to fill the gaps, study and explore their interplay and finally test and validate the procedure. Beyond Precision Cosmology: Dealing with Systematic Errors (BePreSysE) will develop a framework to deal with systematics in forthcoming Cosmological surveys which, could, in principle, be applied beyond Cosmology.

Licia Verde – Universitat de Barcelona (UB)
CoG2016 – Physical Sciences & Engineering (PE9)

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)

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)

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)

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)

GravBHs – A New Strategy for Gravity and Black Holes

General Relativity (GR) encompasses a huge variety of physical phenomena, from the collision of astrophysical black holes, to the dynamics (via holography) of strongly-coupled plasmas and the spontaneous symmetry-breaking in superconductors. Black holes play a central role in all this. However, their equations are exceedingly hard to solve. The apparent lack of a generic tunable parameter that allows to solve the theory perturbatively (like the electric coupling constant in electrodynamics, or the rank of the gauge group in large-N Yang-Mills theory) is arguably the single most important obstacle for generic efficient approaches to the physics of strong gravity and black holes. I argue that one natural parameter suggests itself: GR can be defined in an arbitrary number of dimensions D. Recently I have demonstrated that the limit of large D is optimally tailored for the investigation of black holes, classical and potentially also quantum. Explicit preliminary studies have proved that the concept is sound, powerful, and applicable even in four dimensions. This encourages the pursuit of a full-scale program with two major goals: (A) Reformulating GR and Black Hole physics around the large-D limit in terms of an effective membrane theory of black holes, coupled (non-perturbatively in 1/D) to an effective theory for gravitational radiation. (B) Resolution of outstanding problems in gravitational physics, in particular of problems of direct relevance to cosmic censorship (critical collapse, endpoint of black brane instabilities), and of the quantum theory of black holes. With the new tools of (A), a large number of additional problems in black hole physics and in holographic duality can be solved, which guarantee very substantial fallback objectives. These include black hole collisions, black hole phase diagrams, instabilities, holographic dynamics of finite-temperature systems, and potentially any problem that can be formulated in an arbitrary number of dimensions.

Roberto Emparan – Universitat de Barcelona (UB)
AdG2015 – Physical Sciences & Engineering (PE2)

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)

MUTANOMICS – Determining in vivo protein structures and understanding genetic interactions using deep mutagenesis

The goal of my research is to understand mutations and how they interact to alter phenotypes and disease. We recently initiated a new research direction that uses systematic (‘deep’) mutagenesis to quantify, understand, and predict how diverse mutations interact non-additively within and between molecules to affect phenotypes at multiple scales. Very excitingly, we have also shown that quantifying genetic interactions by deep mutagenesis provides sufficient information to determine the 3D structures of proteins. In this project we will leverage this experience in deep mutagenesis and computational modelling to address three specific aims: 1. To develop simple generic experimental and computational methods to determine the in vivo structures of proteins using deep mutagenesis and to apply these methods to solve the structures of domains of unknown structure. 2. To use deep mutagenesis and computational modelling to understand how mutations globally interact within and between molecules, when these interactions can – and cannot – be predicted from phenotypic measurements alone, and how these interactions alter in response to changes in gene expression. 3. To use deep mutagenesis to understand the cellular toxicity of pathological prion-like domains and to reveal the in vivo structures of these ‘unstructured’ regions, as well as those of disordered proteins that function as agents of protein-based epigenetic inheritance. Taken together, this will provide rich insights into how mutations combine to alter phenotypes, a question of central importance to evolution, engineering, and human disease. It will also develop methods that use deep mutagenesis to determine protein structures, including of intrinsically disordered proteins relevant to disease and epigenetic inheritance. Our goal is to develop techniques that will allow labs across the world to use deep mutagenesis to solve protein structures, including potentially in large-scale systematic projects.

Ben Lehner – Centre de Regulació Genòmica (CRG)
AdG 2019 – Life Sciences (LS2)

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)

STEM-AGING – Tissue regeneration and aging: the decisive quiescent stem-cell state

The basic mechanisms of stem cell malfunction during aging are poorly understood even though they underlie the regenerative decline of most organs and tissues as we age. Based on our recent contributions (Nature 2014, Nature 2016), the fields of tissue regeneration and aging converge on the key role of the quiescent state, the preferred state of stem cells in low turnover tissues such as skeletal muscle. Our unifying hypothesis is that stem-cell quiescence maintenance, which requires active proteostasis (protein homeostasis), lies at the basis of stemness, and that its substitution by a senescence state in aging impairs regeneration. How these variables connect to drive stem cell aging is not known. Crucial experimental systems in this proposal are sensitive reporter mice for proteostasis, senescence and quiescence/fate in aging muscle stem cells. The project is divided as follows: Objective 1. Proteostasis and stem cell quiescence maintenance: tracing proteostasis in quiescent stem cells from autophagy and chaperone-mediated autophagy (CMA) reporter mice during aging / impact of autophagy/CMA loss on quiescence and regeneration / molecular regulators of proteostasis. Objective 2. Proteostasis and quiescent stem cell heterogeneity and fate: asymmetric segregation of proteotoxic waste as an instructor of stem cell heterogeneity and regenerative fate. Objective 3. The quiescence-to-senescence-switch in aging muscle stem cells: tracing and isolating senescent stem cells in senescence-cell reporter mice during aging / impact of senescent cell ablation on regenerating aged muscle. Objective 4. Circadian regulation in the quiescent stem-cell state: impact of aging on circadian rhythms and consequences for quiescence maintenance and regeneration. We expect that completion of these objectives will provide new fundamental knowledge on stem-cell biology, regeneration and aging.

Pura Muñoz-Cánoves – Universitat Pompeu Fabra (UPF)
AdG2016 – Life Sciences (LS4)

PALADYN – New geochemical approach to reconstruct tropical palaeo-atmospheric dynamics

Tropical climates are changing rapidly in the most populated regions of the planet. The changes largely arise from alterations in the Hadley circulation driven by natural and anthropogenic factors, whose relative roles and temporal variability are unclear. These knowledge gaps are in part due to the shortage of methods to study the atmospheric circulation before the advent of instrumental and satellites observations, and compounded by the contradictions between models and palaeo-data. The aim of the project is to develop an innovative palaeo-proxy approach to investigate the natural range of variability of the Hadley circulation during past episodes of extreme warmth and cold. The approach relies on the exploitation as climate proxy of an untapped but widespread material in marine sediments: windborne pyrogenic carbon (PyC) derived from savannah and grassland fires in the tropics. Through the geochemical and isotopic spatial characterization of PyC, along with the analysis of mineral dust in the modern tropical deep ocean, and a PyC biogeochemical model, we will build an interpretative framework of PyC deposition in deep-sea sediments.

Its application in Pliocene-Pleistocene sequences from the Atlantic and the Pacific will allow the reconstruction of past meridional and zonal shifts in the Intertropical Convergence Zone and the Southern hemisphere westerlies, and provide new constraints on the natural variability of the Hadley circulation and associated hydroclimates. PALADYN is possible thanks to the combination of cutting-edge geochemical and satellite data, and GIS methodologies, with in-depth interdisciplinary expertise on the palaeoclimatic study of marine sediments. We will provide new important datasets of windborne deep-sea PyC for testing and refining prediction models of atmospheric circulation, carbon cycle, precipitation and wildfires, issues which are of paramount global importance from scientific as well as societal standpoints.

Antoni Rosell-Melé – Universitat Autònoma de Barcelona (UAB)
AdG2018 – Physical Sciences & Engineering (PE10)

MYCOCHASSIS – Engineering of a minimal bacterial therapeutic chassis

Engineering bacteria to deliver therapeutic agents or to present antigens for vaccination is an emerging area of research with great clinical potential. The most challenging issue in this field is the selection of the right bacteria to engineer, commonly known as “chassis”. The best chassis depends on the application but there is a common drawback in bacteria used nowadays: their complexity and the lack of quantitative information for many reactions which limits genome engineering to classical trial and error approaches. In this project, we want to engineer the genome-reduced bacterium M. pneumoniae using a whole-cell model that will drive the rational to create a chassis for human and animal therapy. Its small size (816 Kbases), the lack of cell wall, and the vast amount of comprehensive quantitative –omics datasets makes this bacterium one of the best candidates for chassis design. By combining bioinformatics, -omics, and biochemistry approaches with genome engineering tools, systems biology analyses, and computational whole-cell models, MYCOCHASSIS aims to: i) develop a whole cell-model based on organism-specific experimental data that will be validated experimentally and that can predict the impact of genome modifications; ii) implement genome engineering tools to delete non-essential pathogenic and virulent elements predicted by the whole-cell model to engineer a therapeutical chassis; iii) using the whole-cell model design and engineer genes and circuits to improve growth rate in a defined medium. iv) as a proof of concept introduce orthogonal gene circuits to secrete peptides and enzymes capable of dissolving in vitro biofilms made by the lung pathogens Pseudomonas aeruginosa and Staphylococus aureus. This project will validate the usefulness of whole-cell models for synthetic biology by modelling multiple genomic modifications orientated to facilitate engineering of biological systems.

Luis Serrano – Centre de Regulació Genòmica (CRG)
AdG2014 – Life Sciences (LS9)

CELLPLASTICITY – New Frontiers in Cellular Reprogramming: Exploiting Cellular Plasticity

Our research group has worked over the years at the interface between cancer and ageing, with a strong emphasis on mouse models. More recently, we became interested in cellular reprogramming because we hypothesized that understanding cellular plasticity could yield new insights into cancer and ageing. Indeed, during the previous ERC Advanced Grant, we made relevant contributions to the fields of cellular reprogramming (Nature 2013), cellular senescence (Cell 2013), cancer (Cancer Cell 2012), and ageing (Cell Metabolism 2012). Now, we take advantage of our diverse background and integrate the above processes. Our unifying hypothesis is that cellular plasticity lies at the basis of tissue regeneration (“adaptive cellular plasticity”), as well as at the origin of cancer (“maladaptive gain of cellular plasticity”) and ageing (“maladaptive loss of cellular plasticity”). A key experimental system will be our “reprogrammable mice” (with inducible expression of the four Yamanaka factors), which we regard as a tool to induce cellular plasticity in vivo. The project is divided as follows: Objective #1 – Cellular plasticity and cancer: role of tumour suppressors in in vivo de-differentiation and reprogramming / impact of transient de-differentiation on tumour initiation / lineage tracing of Oct4 to determine whether a transient pluripotent-state occurs during cancer. Objective #2 – Cellular plasticity in tissue regeneration and ageing: impact of transient de-differentiation on tissue regeneration / contribution of the damage-induced microenvironment to tissue regeneration / impact of transient de-differentiation on ageing. Objective #3: New frontiers in cellular plasticity: chemical manipulation of cellular plasticity in vivo / new states of pluripotency / characterization of in vivo induced pluripotency and its unique properties. We anticipate that the completion of this project will yield new fundamental insights into cancer, regeneration and ageing.

Manuel Serrano – Institut de Recerca Biomèdica (IRB Barcelona)
AdG2014 – Life Sciences (LS4)

SIMBIONT – A data-driven multiscale simulation of organogenesis

Organogensis is the process by which multiple different cell types grow, differentiate and interact with each other (both molecularly and physically) to create large complex structures with integrated functions, such as the heart, brain or limb. Understanding this process has enormous potential impact, both scientifically and medically. The SIMBIONT project represents both a grand technical challenge, and a fundamental scientific question. The grand technical challenge is to build the first ever multi-scale computer model of mammalian organogenesis, specifically limb development. This purpose of the model is to help us address the deep scientific question: How are the complex interactions at multiple scales (genes, molecules, cells and tissues) coordinated so as to build a carefully constructed 3D organ? So far, computer modelling has helped to understand some of the pieces of this puzzle, eg. morphogen gradients, or control of tissue growth. However, putting multiple pieces together into a single multi-scale simulation remains a challenge. We will use the latest state-of-the-art quantitative data-generation techniques (including Tomo-Seq and OPTiSPIM), to gather 3D data at multiple levels: gene expression patterns, cell signaling, cellular growth rates, intercalation patterns, and global tissue movements. In parallel we will develop a new multi-scale modeling framework which can integrate this quantitative data, to simulate both the molecular patterning and the mechanical growth of the developing limb bud. Doing so will allow us to ask new systems-level questions about (i) the molecular control of organ shape, (ii) coordination of patterning and growth, and (iii) the multi-scale robustness of the system. We will test the key predictions of the model experimentally (both with mouse mutants, and in vitro perturbations). SIMBIONT will serve as an example for modeling other complex multicellular processes in the future, eg. tissue engineering and regenerative medicine.

James Sharpe – Centre de Regulació Genòmica (CRG)
AdG2014 – Life Sciences (LS2)

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)

MASCP – Mechanisms of alternative pre-mRNA splicing regulation in cancer and pluripotent cells

Alternative splicing of messenger RNA precursors is a prevalent form of gene regulation that greatly expands the coding capacity and regulatory opportunities of higher eukaryotic genomes. It contributes to cell differentiation and pluripotency and its deregulation promotes cancer progression, as evidenced by the frequent occurrence of cancer-associated mutations in splicing factors, which are also targets of anti-tumor drugs. Despite its prevalence and relevance, the underlying mechanisms of regulation remain poorly understood. This proposal aims to develop and apply systematic approaches that can allow us to carry out the equivalent of genetic analysis of splicing regulation in cancer and pluripotent cells. These technologies can help to unweave the complex network of functional interactions within the spliceosome and of the spliceosome with regulatory factors, exhaustively map the contribution of regulatory sequences and be used to investigate, with unprecedented detail, mechanisms of regulation for essentially any regulator or alternative splicing event operating in a particular cell line. Such approaches can offer a unique opportunity to address key unresolved mechanistic questions, including the molecular basis for positional effects of splicing regulatory factors (RNA Maps), the regulatory potential of the core spliceosome and the integration of alternative splicing with other cell regulatory programs. We will combine these approaches with biochemical and cellular assays to investigate detailed mechanisms of regulation relevant for the control of cell proliferation and/or pluripotency in cancer and induced pluripotent stem (iPS) cells. Progress in this area can contribute to reveal the molecular logic governing a key layer of gene regulation and has the potential to discover novel factors and regulatory circuits that trigger or modulate cell growth, differentiation and cancer progression.

Juan Valcárcel – Centre de Regulació Genòmica (CRG)
AdG2014 – Life Sciences (LS1)

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)

LightNet – Tracking the Coherent Light Path in Photosynthetic Networks

Nature has developed photosynthesis to power life. Networks of light harvesting antennas capture the sunlight to funnel the photonic energy towards reaction centres. Surprisingly, quantum coherences are observed in the energy transfer of photosynthetic complexes, even at room temperature. Does nature exploit quantum concepts? Does the coherence help to find an optimal path for robust or efficient transfer? How are the coherences sustained? What is their spatial extent in a real light-harvesting network? So far only solutions of complexes were studied, far from the natural network operation, putting on hold conclusions as to a biological role of the coherences. My group recently succeeded in the first detection of coherent oscillations of a single photo-synthetic complex at physiological conditions, and non-classical photon emission of individual complexes. These pioneering results, together with our expertise in nanophotonics, pave the way to address photosynthetic networks in real nano-space and on femtosecond timescale. Specific objectives are: –Ultrafast single protein detection: tracing the fs coherent energy transfer path of an individual complex; addressing the very nature of the persistent coherences. -Beyond fluorescence: light harvesting complex are designed for light transport, not emission. I will explore innovative alternatives: optical antennas to enhance quantum efficiency; detection of stimulated emission; and electrical read-out on graphene. -Nanoscale light transport: using local excitation and detection by nanoholes, nanoslits and scanning antenna probes I will spatially map the extent of the inter-complex transfer. -The network: combining both coherent fs excitation and localized nanoscale excitation/detection I will track the extent of coherences throughout the network. The impact of this first exploration of light transport in a nanoscale bionetwork ranges to solar energy management, molecular biology, polymer chemistry and material science.

Niek van Hulst – Institut de Ciències Fotòniques (ICFO)
AdG2014 – Physical Sciences & Engineering (PE3)

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