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)

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

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

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)

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)

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)

ASTRA – ASsembly and phase Transitions of Ribonucleoprotein Aggregates in neurons: from physiology to pathology

Recent works indicate the pathogenic relevance of altered RNA metabolism and aberrant ribonucleoprotein (RNP) assembly in several neurodegenerative diseases, such as Amyotrophic lateral sclerosis. How defective RNPs form, what are their integral components and which events trigger their appearance late in life are still unsolved issues. While emerging evidence indicates that mutations and post-translational modifications of specific RNA-binding proteins (RBPs) induce liquid-solid phase transition in vitro, much less is known about the in vivo properties of RNP assemblies and which role RNA plays in their formation.

ASTRA will combine sophisticated imaging-derived RNP complex purification with innovative computational approaches and powerful genetic tools to unravel the biophysical properties and composition of RBP complexes and how they are modified in disease conditions. Through the development of new imaging and optical methods we plan to study how RNPs separate in liquid and solid phases in cells, in tissues (retina) and animal models and to characterize their RNA and protein components in physiological and pathological states.

Exploiting the novel finding that non-coding RNAs act as scaffolding molecules for RNP assembly, we will investigate how such RNAs control the dynamic link between RNP formation, intracellular sorting and function. In a genuine interdisciplinary team effort, we will reveal how the architecture and localization of cytoplasmic RNP complexes are controlled in motor neurons and affected in neurodegeneration.

We plan to develop novel advanced microscopy methods to monitor formation of aberrant RNPs in vivo and we will explore new molecules to impede pathological cascades driven by RNP assemblies. In conclusion, ASTRA will allow us to gain a comprehensive understanding of RNP function and dysfunction; we will use this knowledge to develop new therapeutic strategies that will impact on several protein-misfolding neurodegenerative diseases.

Gian Gaetano Tartaglia – Centre de Regulació Genòmica (CRG)
SyG 2019 – LS

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)

FoQAL – Frontiers of Quantum Atom-Light Interactions

FoQAL aims to completely re-define our ability to control light-matter interactions at the quantum level. This potential revolution will make use of cold atoms interfaced with nanophotonic systems, exploiting unique features such as control over the dimensionality and dispersion of light, the engineering of quantum vacuum forces, and strong optical fields and forces associated with light confined to the nanoscale. We will develop powerful and fundamentally new paradigms for atomic trapping, tailoring atomic interactions, and quantum nonlinear optics, which cannot be duplicated in macroscopic systems even in principle. Targeted breakthroughs include: 1) Nanoscale traps using quantum vacuum forces. Nanophotonic structures enable strong quantum vacuum forces acting on atoms near dielectric surfaces to be harnessed for novel “vacuum traps.” Their figures of merit (e.g., trap depth and spatial confinement) will exceed what is possible with conventional trapping techniques by 1-2 orders of magnitude. 2) Strong long-range spin-photon-phonon interactions. We will show that nanophotonic systems enable the formation of new “quasi-particles” consisting of atoms dressed by localized photonic clouds. These clouds produce strong multi-physics coupling between photons and atomic spins and motion, facilitating novel long-range interactions and the generation of exotic quantum states of light and matter. 3) New routes to single-photon nonlinear optics. We will develop novel techniques to attain strong interactions between individual photons, which are not based upon the saturation of atomic transitions. These approaches will take advantage of engineered long-range interactions between atoms, and “atom-optomechanics” in which the optical response of atoms and their motion strongly couple. Significantly, our protocols will enable a growth in nonlinearities for moderate atom number N, in contrast to conventional cavity QED where the optimal operating point is N=1.

Darrick Chang – Institut de Ciències Fotòniques (ICFO)
StG2014 – Physical Sciences and Engineering (PE2)

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)

NEURAL AS – Functions and evolutionary impact of transcriptomic novelties in the vertebrate brain

Alternative splicing (AS) is the largest contributor to transcriptomic diversification in metazoans. In particular, mirroring their unparalleled morphological and cellular complexity, vertebrate brains show the highest levels of regulated AS known in nature. However, the functions of most of these alternative transcripts, and the evolutionary impact that the increased transcriptional complexity has had on the evolution of the vertebrate brain are still widely unexplored. In this project, we will investigate the functions and evolutionary impact of neural AS in vertebrates. We will focus on neural-specific alternative exons that are highly conserved across vertebrate groups (suggesting functional importance), but that are not conserved in invertebrates, and are thus vertebrate-specific genomic novelties. We will term these exons Vertebrate- and Neural-specific Alternatively Spliced (VN-AS) exons.

Through a combination of bioinformatics, experimental manipulation in models species, and systems-level network analysis, we aim to: (i) Comprehensively identify VN-AS exons, and study their regulation during vertebrate neurogenesis and nervous system development, using RNA-seq and comparative genomics; (ii) Probe the phenotypic impact of VN-AS exons on vertebrate nervous systems, using the CRISPR-Cas technology for genome editing; and (iii) Investigate how VN-AS exons rewire protein-protein interaction networks in vertebrate neurons – an emergent molecular function for AS –, and whether this rewiring underlies novel functions of VN-AS exons in the vertebrate brains.

This project will thus deliver fundamental insight into two major unanswered questions: (i) what are the functions of transcriptomic diversification, and (ii) how does transcriptomic diversification impact organismal evolution. Our results will fill a large gap of knowledge in our current understanding of brain evolution and development, providing a complementary angle to traditional gene expression studies.

Manuel Irimia – Centre de Regulació Genòmica (CRG)
StG2014 – Life Sciences (LS2)

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)

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)

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 – (PE) Physical Sciences & Engineering

GLOBALMACRO – Global Production Networks and Macroeconomic Interdependence

Researchers and policymakers alike have highlighted the potential efficiency gains of a global production structure. However, such linkages also raise the possibility of risks. This proposal tackles both empirical and theoretical challenges in incorporating the microeconomic structure of trade and international production networks in the study of the propagation of shocks internationally, and their impact on macroeconomic interdependence.

Using newly constructed micro-level datasets, I provide quantitative analysis of the importance of the linkages in multicountry general equilibrium models of trade.
First, using firm export and imported-input linkages, I provide a novel model-based estimation strategy to identify the role of country and firm-level shocks, and the implications of these estimates for the transmission of shocks across borders. By using structural trade models to estimate shocks at the firm level and studying the implications for the transmission of shocks across borders, I help bridge the micro-macro nexus in international economics.
Second, I take an even more granular focus by studying the role of firm-to-firm production linkages in transmitting shocks across countries. To do so, I exploit a novel matching procedure between a country’s administrative dataset and cross-country firm-level data. I further build on these data by adding in domestic bank-firm relationships. This strategy allows for the study of how financial shocks are exported abroad via firms’ trade and multinational linkages.
Third, I incorporate the insights from the empirical work into a full-scale multicountry general equilibrium model of trade, which allows for firm-level heterogeneity and microeconomic and macroeconomics shocks. I use the model for a quantitative study of the cross-country transmission of the different shocks via trade. This allows me to perform counterfactuals and examine the impact of policies, such as how opening to trade impacts macroeconomic interdependence.

Julian di Giovanni – Universitat Pompeu Fabra (UPF)
CoC2016 – (SH) Social Sciences & Humanities

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)

LATTAL – The Latin Talmud and its Influence on Christian-Jewish Polemic

While polemics and dialogue between Judaism and Christianity are as old as the Christian religion itself, one can clearly distinguish different periods, trends and intensities in the relations between the faiths. A significant landmark in this long and complex history is the Latin translation of large sections of the Talmud, the most important Jewish post-biblical text and the basis for the development of Rabbinic Judaism. When during the 13th century Christian theologians started to examine and translate the Talmud from Hebrew and Aramaic into Latin, they were faced with a huge body of texts which represented centuries of legalistic and homiletic materials. The discovery of this immense post-biblical Jewish literature became a source of fascination for Christians who believed that this text, which encompasses every aspect of Jewish life, was fundamental both for refuting the Jewish faith and for substantiating the truth of Christianity. This realization heralded a rethinking of the place of Jews in Christian society and redefined Christian-Jewish dialogue and polemic.

The purpose of our project is to edit and publish the largest extant collection of Talmudic passages translated from Hebrew into Latin, that is, the “”Extractiones de Talmud””, while studying this ground-breaking document in the context of the trial and burning of the Talmud in 1240-42 and its aftermath. This project addresses vital questions of Jewish and Christian identity, still relevant to the 21st century, and can only be carried out by a transdisciplinary research team including specialists from Latin Philology, Hebrew Studies and History.

Alexander Fidora – Universitat Autònoma de Barcelona (UAB)
CoG2013 – Social Sciences & Humanities (SH5)

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)

BIGSEA – Biogeochemical and ecosystem interactions with socio-economic activity in the global ocean

The global marine ecosystem is being deeply altered by human activity. On the one hand, rising concentrations of atmospheric greenhouse gases are changing the physical and chemical state of the ocean, exerting pressure from the bottom up. Meanwhile, the global fishery has provided large economic benefits, but in so doing has restructured ecosystems by removing most of the large animal biomass, a major top-down change. Although there has been a tremendous amount of research into isolated aspects of these impacts, the development of a holistic understanding of the full interactions between physics, chemistry, ecology and economic activity might appear impossible, given the myriad complexities. This proposal lays out a strategy to assemble a team of trans-disciplinary expertise, that will develop a unified, data-constrained, grid-based modeling framework to represent the most important interactions of the global human-ocean system. Building this framework requires solving a series of fundamental problems that currently hinder the development of the full model. If these problems can be solved, the resulting model will reveal novel emergent properties and open the doors to a range of previously unexplored questions of high impact across a range of disciplines. Key questions include the ways in which animals interact with oxygen minimum zones with implications for fisheries, the impacts fish harvesting may have on nutrient recycling, spatio-temporal interactions between managed and unmanaged fisheries, and fundamental questions about the relationships between fish price, fishing cost, and multiple markets in a changing world. Just as the first coupled ocean-atmosphere models revealed a wealth of new behaviours, the coupled human-ocean model proposed here has the potential to launch multiple new fields of enquiry. It is hoped that the novel approach will contribute to a paradigm shift that treats human activity as one component within the framework of the Earth System.

Eric Galbraith – Universitat Autònoma de Barcelona (UAB)
CoG2015 – Physical Sciences & Engineering (PE10)

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)

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)

GREENLIGHT_REDCAT – Towards a Greener Reduction Chemistry by Using Cobalt Coordination Complexes as Catalysts and Light-driven Water Reduction as a Source of Reductive Equivalents

The development of alternative greener synthetic methods to transform renewable feedstocks into elaborated chemical structures mediated by solar light is a prerequisite for a future sustainable society. In this regard, this project entails the use of visible light as driving force and water as a source of hydrides for the synthesis of high-value chemicals. The project merges photoredox catalysis with 1st row transition coordination complexes catalysis to open a new avenue for greener selective catalytic reduction processes for organic substrates. The ground-breaking nature of the project is: A) Develop light-driven region- and/or enantioselective catalytic reductions using well-defined cobalt coordination complexes with aminopyridine ligands, initially developed for water reduction. Sterics, electronics and supramolecular interactions (apolar cavities and chiral pockets) will be studied to proper control of the selectivity in the reduction of i) C=E and C=C bonds and ii) in the C-C inter- and intramolecular reductive homo- or heterocouplings. B) Fundamental understanding of the light-driven cobalt catalysed reductions characterizing intermediates that are involved in the reactivity, kinetics and labelling studies as well as performing computational modelling of reaction mechanisms. The basic understanding of operative mechanisms will expedite a new methodology for electrophile-electrophile umpolung couplings. C) Enhance catalytic performance of the light-driven cobalt catalysed reductions by self-assembling of catalyst-photosensitizer into carbon based pi-conjugated materials through noncovalent supramolecular interactions. Likewise, it will allow electrode immobilization for electrocatalysed reductions using water as a source of protons and electrons. As a proof of concept, cobalt catalysts based on aminopyridine ligands have been shown highly active in the light-driven reduction of ketones and aldehydes to alcohols, using water as the source of hydrogen atom.

Julio Lloret – Institut Català d’Investigació Química (ICIQ)
CoG2014 – Physical Sciences & Engineering (PE5)

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)

InanoMOF – Multifunctional micro- and nanostructures assembled from nanoscale metal-organic frameworks and inorganic nanoparticles

In InanoMOF, we aim to develop frontier Supramolecular and Nanochemistry methodologies for the synthesis of a novel class of structures via controlled assembly of nanoscale metal-organic frameworks (nanoMOFs) and inorganic nanoparticles (INPs). These methods will embody the premise that “controlled object-by-object nano-assembly is a ground-breaking approach to explore for producing systems of higher complexity with advanced functions”. The resulting hybrid nanoMOF@INPs will marry the unique properties of INPs (magnetism of iron oxide NPs and optics of Au NPs) to the functional porosity of MOFs.

The first part of InanoMOF encompasses the design, synthesis-assembly and characterisation of nanoMOF@INPs – advanced MOF-based sorbents that incorporate the functionality of the INPs used: magnetically controlled movement, in vivo detectability, enhanced biocompatibility and porosity, pollutant removal, or controlled sorption/delivery.

The second part of InanoMOF entails studying the physicochemical properties of the synthesised nanoMOF@INPs and ascertaining their utility as drug-delivery/theranostic systems and as magnetic sorbents for pollutant removal. Specifically, we will study their stability in working media and determine their capacities for drug or pollutant sorption/delivery capacities.

As proof-of-concept, we will study their toxicity in vitro and in vivo; enhancement of their in vitro therapeutic efficacy; and their capacity to remove pollutants (in real water and gasoline/diesel fuel samples) via magnetic assistance. In InanoMOF we will endeavour to establish the synthetic bases for controlling the spatial ordering of nanoMOF crystals, whether alone or combined with other nanomaterials (e.g. INPs, graphene, etc.). We are confident that our work will ultimately enable researchers to create MOF-based composites having cooperative and synergistic properties and functions for myriad applications (e.g. heterogeneous catalysis, sensing and separation).

Daniel Maspoch – Institut Català de Nanociència i Nanotecnologia (ICN2)
CoG2013 – Physical Sciences & Engineering (PE5)

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.

Pablo 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)

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)

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)

QnanoMECA – Quantum Optomechanics with a levitating nanoparticle

Micro- and nano-mechanical oscillators with high quality (Q)-factors have gained much interest for their capability to sense very small forces. Recently, this interest has exponentially grown owing to their potential to push the current limits of experimental quantum physics and contribute to our further understanding of quantum effects with large objects. Despite recent advances in the design and fabrication of mechanical resonators, their Q-factor has so far been limited by coupling to the environment through physical contact to a support. This limitation is foreseen to become a bottleneck in the field which might hinder reaching the performances required for some of the envisioned applications. A very attractive alternative to conventional mechanical resonators is based on optically levitated nano-objects in vacuum. In particular, a nanoparticle trapped in the focus of a laser beam in vacuum is mechanically disconnected from its environment and hence does not suffer from clamping losses. First experiments on this configuration have confirmed the unique capability of this approach and demonstrated the largest mechanical Q-factor ever observed at room temperature.

The QnanoMECA project aims at capitalizing on the unique capability of optically levitating nanoparticles to advance the field of optomechanics well beyond the current state-of-the-art. The project is first aimed at bringing us closer to ground-state cooling at room temperature. We will also explore new paradigms of optomechanics based on the latest advances of nano-optics. The unique optomechanical properties of the developed systems based on levitated nanoparticles will be used to explore new physical regimes whose experimental observation has been so far hindered by current experimental limitations.

Romain Quidant – Institut de Ciències Fotòniques (ICFO)
CoG2014 – Physical Sciences & Engineering (PE2)

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)

HISTROOTS – Historical roots of conflict and development: from prehistory ot the colonization experience

I plan to study the effect of history on conflict and economic development with two historical microscopes. Following the lead of the new institutional economics, part of the literature argues that institutions cause differences in productivity and factor endowments which, in turn, explain economic development. An alternative view assumes that human capital shapes institutional changes and, therefore, institutions are endogenous. In the first part of the project, which is the core of the research proposal, I will try to move one step further in this debate by taking an approach that uses administrative data on the first colonizers of Latin America. The data contain some personal characteristics on each of the settlers from 1492 to 1599 (town of origin in Spain, occupation, education, city of arrival in the Americas, etc). Using within-country analysis, since we have information on the precise destinations of the first “pobladores” (settlers), and the different institutional set-ups during the first years of colonization for different geographical areas in Latin America, I will reexamine the issue of institutions versus human capital in the explanation of economic development and conflict. The institutions in the initial times of colonization were not the same in all the regions of Latin America and, in many cases, represented an evolution of pre-Colombian institutions. The new data allows also the analysis of the interaction between human capital and institutions in the initial times. In addition the migrations and the evolution of institutions during the first century of colonization provide also some guidance for the research on the sources of institutional persistence. In the second part I plan to go further back in time to understand how very old conflicts influence current conflict. I will construct a dataset with the location of old conflicts using archaeological evidence to analyze the dynamics of conflict by regions in the very long run.

Marta Reynal – Universitat Pompeu Fabra (UPF)
Cog2014 – Social Sciences & Humanities (SH1)

Forecasting – New Methods and Applications for Forecast Evaluation

Forecasting is a fundamental tool in Economics, Statistics, Business and other sciences. Judging whether forecasts are good and robust is of great importance since forecasts are used everyday to guide policymakers’ and practitioners’ decisions. The proposal aims at addressing four important issues that researchers encounter in practice. A first issue is how to assess whether forecasts are optimal in the presence of instabilities. Optimality is an important property of models’ forecasts: if forecasts are not optimal, then the model can be improved. Existing methods to assess forecast optimality are not robust to the presence of instabilities, which are widespread in the data. How to obtain such robust methods and what they tell us about widely used economic models’ forecasts is the first task of this project.

A second problem faced by forecasters in practice is to evaluate density forecasts. Density forecasts are important tools for policymakers since they quantify uncertainty around forecasts. However, existing methodologies focus on a null hypothesis that is not necessarily the one of interest to the forecaster. The second task is to develop tests for forecast density evaluation that address forecasters’ needs.

A third, important question is “Why Do We Use Forecast Tests To Evaluate Models’ Performance?” The third task of this project is to understand the relationship between traditional in-sample and forecast evaluation tests, and develop a framework that helps to understand under which circumstances forecast tests are more useful than typical in-sample tests.

A final question is how researchers can improve models that do not forecast well. Model misspecification is widespread, still economists are often left wondering exactly which parts of their models are misspecified. The fourth task is to propose an empirical framework for addressing this issue. By estimating time-varying wedges, we assess where misspecification is located, and how important it is.

Barbara Rossi – Universitat Pompeu Fabra (UPF)
CoG2013 – Social Sciences & Humanities (SH1)

PREMETAZOANEVOLUTION – Unravelling the unicellular prehistory of metazoans with functional analyses and single-cell genomics

How multicellular animals (metazoans) emerged from their single-celled ancestor remains a long-standing evolutionary question. Recent genome data has shown that the unicellular ancestor of metazoans already had a complex gene repertoire for genes involved in cell adhesion, cell signaling and transcriptional regulation, including integrins, cadherins, T-box genes, and protein tyrosine kinases. Thus, besides a few metazoan-specific genes, gene co-option and, probably, an increase in gene regulation played important roles into the origin of Metazoa. However, the lack of genetic tools among metazoan’s closest relatives has so far precluded further investigations at the molecular level. Our recent establishment, for the first time, of transgenesis methodologies in two close unicellular relatives of metazoans (both the ichthyosporean Creolimax fragrantissima and the filasterean Capsaspora owczarzaki), allow us to approach these questions in ways that were not previously possible. Thus, we aim to push forward these two model systems and infer, by cell biology and functional genomics, the ancestral function of those genes key to multicellularity in order to understand how they were co-opted for new multicellular functions.

In addition, we will analyze the regulation of the different cell stages and the colony formation (syncitial and aggregative multicellularity) in these two organism by functional genomics and identify when and how the metazoan histone code (an important regulatory layer of gene expression) evolved by analyzing the histone code in these taxa. Finally, to understand the ecology, distribution and adaptation of these unicellular taxa we will obtain the complete genome sequence of uncultured lineages by using single-cell genomics. This research will not only markedly improve our understanding of a major biological question (the origin of metazoan multicellularity) but will also generate new data relevant to a broad range of researchers.

Iñaki Ruiz Trillo – Institut de Biologia Evolutiva (CSIC-IBE)
CoG2013 – Life Sciences (LS8)

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)

CONCERT – Description of information transfer across macromolecules by concerted conformational changes

Signal transduction in biology relies on the transfer of information across biomolecules by concerted conformational changes that cannot currently be characterized experimentally at high resolution. In CONCERT we will develop a method based on the use of nuclear magnetic resonance spectroscopy in solution that will provide very detailed descriptions of such changes by using the information about structural heterogeneity contained in a parameter that is exquisitely sensitive to molecular shape called residual dipolar coupling measured in steric alignment. To show how this new method will allow the study of information transfer we will determine conformational ensembles that will report on the intra and inter-domain concerted conformational changes that activate the androgen receptor, a large allosteric multi-domain protein that regulates the male phenotype and is a therapeutic target for castration resistant prostate cancer, the condition suffered by prostate cancer patients that have become refractory to hormone therapy, the first line of treatment for this disease.

To complement the structural information obtained by nuclear magnetic resonance and, especially, measure the rate of information transfer across the androgen receptor we will carry out in a collaborative fashion high precision single molecule Förster resonance energy transfer and fluorescence correlation spectroscopy experiments on AR constructs labelled with fluorescent dyes. In summary we will develop a method that will make it possible to describe some of the most fascinating biological phenomena, such as allostery and signal transduction, and will, in the long term, be an instrument for the discovery of drugs to treat castration resistant prostate cancer, a late stage of prostate cancer that is incurable and kills ca. 70.000 European men every year.

Xavier Salvatella – Institut de Recerca Biomèdica (IRB Barcelona)
CoG2014 – Physical and Engineering Sciences (PE4)

SPIN-PORICS – Merging Nanoporous Materials with Energy-Efficient Spintronics

This Project aims to integrate engineered nanoporous materials into novel energy-efficient spintronic applications. Magnetic storage and magneto-electronic devices are conventionally controlled by means of magnetic fields (via electromagnetic induction) or using spin-polarized electric currents (spin-transfer torque). Both principles involve significant energy loss by heat dissipation (Joule effect). The replacement of electric current with electric field would drastically reduce the overall power consumption. Strain-mediated magneto-electric coupling in piezoelectric-magnetostrictive bilayers might appear a proper strategy to achieve this goal. However, this approach is not suitable in spintronics because of the clamping effects with the substrate, need of epitaxial interfaces and risk of fatigue-induced mechanical failure. The exciting possibility to control ferromagnetism of metals and semiconductors directly with electric field (without strain) has been recently reported, but most significant effects occur below 300 K and only in ultra-thin films or nanoparticles.

This Project tackles the development of a new type of nanocomposite material, comprising an electrically conducting or semiconducting nanoporous layer filled with a suitable dielectric material, where the magnetic properties of the metal/semiconductor will be largely tuned at room temperature (RT) by simply applying a voltage, via electric charge accumulation. The porous layer will consist of specific alloys (Cu-Ni or Fe-Rh) or oxide diluted magnetic semiconductors, where surface magnetic properties have been recently reported to be sensitive to electric field at RT. Based on these new materials, three technological applications are envisaged: electrically-assisted magnetic recording, voltage-driven switching of magnetic random-access memories and spin field-effect transistors. The obtained results are likely to open new paradigms in the field of spintronics and could be of high economic transcendence.

Jordi Sort – Universitat Autònoma de Barcelona (UAB)
CoG2014 – Physical Sciences & Engineering (PE8)

Mycinhibinclinic – Pushing Myc inhibition towards the clinic

Deregulation of the Myc oncogene promotes tumorigenesis in most if not all cancers and is often associated with poor prognosis. However, targeting Myc has long been considered impossible because of potential catastrophic side effects in normal tissues. Despite this general assumption, we showed that Myc inhibition displays extraordinary therapeutic benefit in various transgenic mouse models of cancer, and caused only mild, well-tolerated and reversible side effects in normal tissues. For these studies we have employed a dominant negative of Myc, called Omomyc, which we designed and validated, and that is able to inhibit Myc transactivation function both in vitro and in vivo. Omomyc has so far been utilized exclusively as gene therapy and served the purpose of pre-clinically validating the therapeutic impact of systemic Myc inhibition. In this proposal we intend to push such a therapeutic approach further towards the clinic, making use of 1. Omomyc-based Cell Penetrating Peptides (CPPs): a novel, state-of-the-art potential method for directly utilising Omomyc itself (or a similar peptide) as a drug; 2. A new generation of Myc inhibitory small molecules generated by our collaborators at the Roswell Park Cancer Center. Our study in different mouse models of cancer will provide a comprehensive preclinical validation of such innovative therapies and will potentially boost our therapeutic arsenal against the majority of human cancers.

Laura Soucek – Valle d’Hebron Institut d’Oncologia (VHIO)
CoG2013 – Life Sciences (LS7)

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)

TensionControl – Multiscale regulation of epithelial tension

Throughout development and adult life, the growth and remodelling of living tissues is determined by a complex interplay between chemical and physical cues. Among such physical cues, mechanical tension is emerging as central regulator of cellular fate and function. To explain tension regulation, current research emphasizes molecular mechanisms at an ever increasing level of detail. How these local mechanisms are integrated to give rise to global patterns of tissue tension is unknown, however. The goal of this project is to provide a multiscale understanding of tension regulation within epithelial cell monolayers. We propose two pairs of competing mechanisms for tension regulation: fluidization vs. reinforcement and cell division vs. apoptosis. These competing mechanisms are inherently multiscale in the sense that they span and couple multiple levels of tissue organization, from the local actomyosin contraction to the multicellular rearrangement. For each of these competing mechanisms we plan to study how local processes and interactions give rise to global tensional patterns. To do this, we propose to develop an integrated experimental setup to map and perturb monolayer tension at different length scales. We expect this project to unveil the repertoire of mechanisms that epithelial tissues use to regulate their tension and dynamics.

Xavier Trepat – Institut de Bioenginyeria de Catalunya (IBEC)
CoG2013 – Life Sciences (LS3)

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)

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)

editCRC – A genome editing-based approach to study the stem cell hierarchy of human colorectal cancers

A hallmark of cancer is tumor cell heterogeneity, which results from combinations of multiple genetic and epigenetic alterations within an individual tumor. In contrast, we have recently discovered that most human colorectal cancers (CRCs) are composed of mixtures of phenotypically distinct tumor cells organized into a stem cell hierarchy that displays a striking resemblance to the healthy colonic epithelium. We showed that long-term regeneration potential of tumor cells is largely influenced by the position that they occupy within the tumor’s hierarchy. To analyze the organization of CRCs without the constraints imposed by tumor cell transplantation experiments, we have developed a method that allows for the first time tracking and manipulating the fate of specific cell populations in whole human tumors. This technology is based on editing the genomes of primary human CRCs cultured in the form of tumor organoids using Zinc-Finger Nucleases to knock-in either lineage tracing or cell ablation alleles in genes that define colorectal cancer stem cells (CRC-SCs) or differentiated-like tumor cells. Edited tumor organoids generate CRCs in mice that reproduce the tumor of origin while carrying the desired genetic modifications.

This technological advance opens the gate to perform classical genetic and developmental analysis in human tumors. We will exploit this advantage to address fundamental questions about the cell heterogeneity and organization of human CRCs that cannot be tackled through currently existing experimental approaches such as: Are CRC-SCs the only tumor cell population with long term regenerating potential? Can we cure CRC with anti-CRC-SC specific therapies? Will tumor cell plasticity contribute to the regeneration of the CRC-SC pool after therapy? Do quiescent-SCs regenerate CRC tumors after standard chemotherapy? Can we identify these cells? How do common genetic alterations in CRC influence the CRC hierarchy? Do they affect the stem cell phenotype?

Eduard Batlle – Institut de Recerca Biomèdica (IRB Barcelona)
AdG2014 – Life Sciences (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)

RISK AND DIVERSITY – Labor Market Risk and Skill Diversity: Implications for Efficiency, Policy, and Estimation

Labor market risk and skill diversity are central features of the labor market. Arguably, employment risk is one of the biggest sources of uncertainty most individuals face in their life time. Likewise, exploiting the synergies and complementarities between differentially skilled workers is amongst the greatest challenges to firms’ hiring decisions. The objective is to analyze the efficiency properties and as a consequence evaluate the role for policy. In order to establish the implications of the mechanisms that govern risk and diversity, I elaborate on concrete applications and discuss estimation in different labor market settings. In the presence of Labor Market Risk I address the question how asset holdings exacerbate wage inequality. Workers are exposed to the risk of unemployment, and workers with few assets will trade off the lower riskiness of a job against lower wages. Different asset holdings translate into different wages, thus amplifying inequality due to assets with wage inequality. The proposed analysis of unemployment risk can solve for an equilibrium model that incorporates the distribution of assets, while at the same time allowing for heterogeneity in skills. There is no doubt that fully understanding the asset-skill tradeoff is of primary importance for labor market policy. I then study a different angle of labor market risk, namely risk that is due to matching stochastic types, which introduces ex post mismatch. Ex ante, agents match based on the distribution of possible realizations of ex post types. This model is conducive to identification of complementarities between workers and the value of risk sharing. Skill Diversity, or the allocation of differentially skilled workers across firms of different productivity, is a central feature of the labor market. The aim of this research is to embed the optimal worker composition within firms into standard macro environments to study technological change, information aggregation and spatial diversity.

Jan Eeckhout – Universitat Pompeu Fabra (UPF)
AdG2013 – 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)

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)

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)

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)

CDAC – The role of consciousness in adaptive behavior: A combined empirical, computational and robot based approach

Understanding the nature of consciousness is one of the grand outstanding scientific challenges and two of its features stand out: consciousness is defined as the construction of one coherent scene but this scene is experienced with a delay relative to the action of the agent and not necessarily the cause of actions and thoughts. Did evolution render solutions to the challenge of survival that includes epiphenomenal processes? The Conscious Distributed Adaptive Control (CDAC) project aims at resolving this paradox by using a multi-disciplinary approach to show the functional role of consciousness in adaptive behaviour, to identify its underlying neuronal principles and to construct a neuromorphic robot based real-time conscious architecture. CDAC proposes that the shift from surviving in a physical world to one that is dominated by intentional agents requires radically different control architectures combining parallel and distributed control loops to assure real-time operation together with a second level of control that assures coherence through sequential coherent representation of self and the task domain, i.e. consciousness. This conscious scene is driving dedicated credit assignment and planning beyond the immediately given information. CDAC advances a comprehensive framework progressing beyond the state of the art and will be realized using system level models of a conscious architecture, detailed computational studies of its underlying neuronal substrate focusing, empirical validation with a humanoid robot and stroke patients and the advancement of beyond state of the art tools appropriate to the complexity of its objectives. The CDAC project directly addresses one of the main outstanding questions in science: the function and genesis of consciousness and will advance our understanding of mind and brain, provide radically new neurorehabilitation technologies and contribute to realizing a new generation of robots with advanced social competence.

Paul Verschure – Institut de Bioenginyeria de Catalunya (IBEC)
AdG2013 – Social Sciences & Humanitites (SH4)

4D-GENOME – Dynamics of human genome architecture in stable and transient gene expression changes

The classical view of genomes as linear sequences has been replaced by a vision of nuclear organization that is both dynamic and complex, with chromosomes and genes non-randomly positioned in the nucleus. Process compartmentalization and spatial location of genes modulate the transcriptional output of the genomes. However, how the interplay between genome structure and gene regulation is established and maintained is still unclear. The aim of this project is to explore whether the genome 3D structure acts as an information source for modulating transcription in response to external stimuli. With a genuine interdisciplinary team effort, we will study the conformation of the genome at various integrated levels, from the nucleosome fiber to the distribution of chromosomes territories in the nuclear space. We will generate high-resolution 3D models of the spatial organization of the genomes of distinct eukaryotic cell types in interphase to identify differences in the chromatin landscape. We will follow the time course of structural changes in response to cues that affect gene expression either permanently or transiently. We will analyze the changes in genome structure during the stable trans-differentiation of immortalized B cells to macrophages and during the transient hormonal responses of differentiated cells. We plan to establish novel functional strategies, based on targeted and high-throughput reporter assays, to assess the relevance of the spatial environment on gene regulation. Using sophisticated modeling and computational approaches, we will combine high-resolution data from chromosome interactions, super-resolution images and omics information. Our long-term plan is to implement a 3D browser for the comprehensive mapping of chromatin properties and genomic features, to better understand how external signals are integrated at the genomic, epigenetic and structural level to orchestrate changes in gene expression that are cell specific and dynamic.

Marc Martí-Renom – Centre de Regulació Genòmica (CRG)
SyG 2013 – SyG6

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