ERC FUNDED PROJECTS

"The A2C2 project treats two major challenges in climate and atmospheric research: the time dependence of the climate attractor to external forcings (solar, volcanic eruptions and anthropogenic), and the attribution of extreme climate events occurring in the northern extra-tropics. The main difficulties are the limited climate information, the computer cost of model simulations, and mathematical assumptions that are hardly verified and often overlooked in the literature. A2C2 proposes a practical framework to overcome those three difficulties, linking the theory of dynamical systems and statistics. We will generalize the methodology of flow analogues to multiple databases in order to obtain probabilistic descriptions of analogue decompositions. The project is divided into three workpackages (WP). WP1 embeds the analogue method in the theory of dynamical systems in order to provide a metric of an attractor deformation in time. The important methodological step is to detect trends or persisting outliers in the dates and scores of analogues when the system yields time-varying forcings. This is done from idealized models and full size climate models in which the forcings (anthropogenic and natural) are known. A2C2 creates an open source toolkit to compute flow analogues from a wide array of databases (WP2). WP3 treats the two scientific challenges with the analogue method and multiple model ensembles, hence allowing uncertainty estimates under realistic mathematical hypotheses. The flow analogue methodology allows a systematic and quasi real-time analysis of extreme events, which is currently out of the reach of conventional climate modeling approaches. The major breakthrough of A2C2 is to bridge the gap between operational needs (the immediate analysis of climate events) and the understanding long-term climate changes. A2C2 opens new research horizons for the exploitation of ensembles of simulations and reliable estimates of uncertainty."

1 491 457 €

Start date: 2014-03-01, End date: 2019-02-28

Rapid changes in ocean circulation and climate have been observed in marine sediment and ice cores, notably over the last 60 thousand years (ky), highlighting the non-linear character of the climate system and underlining the possibility of rapid climate shifts in response to anthropogenic greenhouse gas forcing. To date, these rapid changes in climate and ocean circulation are still not fully explained. Two main obstacles prevent going beyond the current state of knowledge: - Paleoclimatic proxy data are by essence only indirect indicators of the climatic variables, and thus can not be directly compared with model outputs; - A 4-D (latitude, longitude, water depth, time) reconstruction of Atlantic water masses over the past 40 ky is lacking: previous studies have generated isolated records with disparate timescales which do not allow the causes of circulation changes to be identified. Overcoming these two major limitations will lead to major breakthroughs in climate research. Concretely, I will create the first database of Atlantic deep-sea records over the last 40 ky, and extract full climatic information from these records through an innovative model-data integration scheme using an isotopic proxy forward modeling approach. The novelty and exceptional potential of this scheme is twofold: (i) it avoids hypotheses on proxy interpretation and hence suppresses or strongly reduces the errors of interpretation of paleoclimatic records; (ii) it produces states of the climate system that best explain the observations over the last 40 ky, while being consistent with the model physics. Expected results include: • The elucidation of the mechanisms explaining rapid changes in ocean circulation and climate over the last 40 ky, • Improved climate model physics and parameterizations, • The first projections of future climate changes obtained with a model able to reproduce the highly non linear behavior of the climate system observed over the last 40 ky.

3 000 000 €

Start date: 2014-02-01, End date: 2019-01-31

"Children learn any language that they grow up with, adapting to any of the ca. 7000 languages of the world, no matter how divergent or complex their structures are. What cognitive processes make this extreme flexibility possible? This is one of the most burning questions in cognitive science and the ACQDIV project aims at answering it by testing and refining the following leading hypothesis: Language acquisition is flexible and adaptive to any kind of language because it relies on a small set of universal cognitive processes that variably target different structures at different times during acquisition in every language. The project aims at establishing the precise set of processes and at determining the conditions of variation across maximally diverse languages. This project focuses on three processes: (i) distributional learning, (ii) generalization-based learning and (iii) interaction-based learning. To investigate these processes I will work with a sample of five clusters of languages including longitudinal data of two languages each. The clusters were determined by a clustering algorithm seeking the structurally most divergent languages in a typological database. The languages are: Cluster 1: Slavey and Cree, Cluster 2: Indonesian and Yucatec, Cluster 3: Inuktitut and Chintang, Cluster 4: Sesotho and Russian, Cluster 5: Japanese and Turkish. For all languages, corpora are available, except for Slavey where fieldwork is planned. The leading hypothesis will be tested against the acquisition of aspect and negation in each language of the sample and also against the two structures in each language that are most salient and challenging in them (e. g. complex morphology in Chintang). The acquisition processes also depend on statistical patterns in the input children receive. I will examine these patterns across the sample with respect to repetitiveness effects, applying data-mining methods and systematically comparing child-directed and child-surrounding speech."

1 998 438 €

Start date: 2014-09-01, End date: 2019-08-31

This proposal is focused in the areas of chemical medicine and chemical biology with the key drivers being the discovery and development of new materials that have practical functionality and application. The project will enable the fabrication of thousands of three-dimensional “smart-polymers” that will allow: (i). The precise and controlled release of drugs upon the addition of either a small molecule trigger or in response to disease, (ii). The discovery of materials that control and manipulate cells with the identification of scaffolds that provide the necessary biochemical cues for directing cell fate and drive tissue regeneration and (iii). The development of new classes of “smart-polymers” able, in real-time, to sense and report bacterial contamination. The newly discovered materials will find multiple biomedical applications in regenerative medicine and biotechnology ranging from 3D cell culture, bone repair and niche stabilisation to bacterial sensing/removal, while offering a new paradigm in drug delivery with biomarker triggered drug release.

2 310 884 €

Start date: 2014-11-01, End date: 2019-10-31

"This proposal aims at strengthening the connections between more fundamentally oriented areas of mathematics like algebra, geometry, analysis, and topology, and the more applied oriented and more recently emerging disciplines of discrete mathematics, optimization, and algorithmics. The overall goal of the project is to obtain, with methods from fundamental mathematics, new effective tools to unravel the complexity of structures like graphs, networks, codes, knots, polynomials, and tensors, and to get a grip on such complex structures by new efficient characterizations, sharper bounds, and faster algorithms. In the last few years, there have been several new developments where methods from representation theory, invariant theory, algebraic geometry, measure theory, functional analysis, and topology found new applications in discrete mathematics and optimization, both theoretically and algorithmically. Among the typical application areas are networks, coding, routing, timetabling, statistical and quantum physics, and computer science. The project focuses in particular on: A. Understanding partition functions with invariant theory and algebraic geometry B. Graph limits, regularity, Hilbert spaces, and low rank approximation of polynomials C. Reducing complexity in optimization by exploiting symmetry with representation theory D. Reducing complexity in discrete optimization by homotopy and cohomology These research modules are interconnected by themes like symmetry, regularity, and complexity, and by common methods from algebra, analysis, geometry, and topology."

2 001 598 €

Start date: 2014-01-01, End date: 2018-12-31

"By 2040, the European population aged over 60 will rise to 290 million, with those estimated to have dementia to 15.9 million. These dramatic demographic changes will pose huge challenges to health care systems, hence a detailed understanding of age-related cognitive and neurobiological changes is essential for helping elderly populations maintain independence. However, while existing research into cognitive ageing has carefully characterised developmental trajectories of functions such as memory and processing speed, one key cognitive ability that is particularly relevant to everyday functioning has received very little attention: In surveys, elderly people often report substantial declines in navigational abilities such as problems with finding one’s way in a novel environment. Such deficits severely restrict the mobility of elderly people and affect physical activity and social participation, but the underlying behavioural and neuronal mechanisms are poorly understood. In this proposal, I will take a new approach to cognitive ageing that will bridge the gap between animal neurobiology and human cognitive neuroscience. With support from the ERC, I will create a team that will characterise the mechanisms mediating age-related changes in navigational processing in humans. The project will focus on three structures that perform key computations for spatial navigation, form a closely interconnected triadic network, and are particularly sensitive to the ageing process. Crucially, the team will employ an interdisciplinary methodological approach that combines mathematical modelling, brain imaging and innovative data analysis techniques with novel virtual environment technology, which allows for rigorous testing of predictions derived from animal findings. Finally, the proposal also incorporates a translational project aimed at improving spatial mnemonic functioning with a behavioural intervention, which provides a direct test of functional relevance and societal impact."

1 318 990 €

Start date: 2014-01-01, End date: 2018-12-31

Acute Myeloid Leukemia (AML), the most common leukemia diagnosed in adults, represents the paradigm of resistance to front-line therapies in hematology. Indeed, AML is so genetically complex that only few targeted therapies are currently tested in this disease and chemotherapy remains the only standard treatment for AML since the past four decades. Despite an initial sustained remission achieved by chemotherapeutic agents, almost all patients relapse with a chemoresistant minimal residual disease (MRD). The goal of my proposal is to characterize the still poorly understood biological mechanisms underlying persistence and emergence of MRD. MRD is the consequence of the re-expansion of leukemia-initiating cells that are intrinsically more resistant to chemotherapy. This cell fraction may be stochastically more prone to survive front-line therapy regardless of their mutational status (the stochastic model), or genetically predetermined to resist by virtue of a collection of chemoprotective mutations (the mutational model). I have already generated in mice, by consecutive rounds of chemotherapy, a stochastic MLL-AF9-driven chemoresistance model that I examined by RNA-sequencing. I will pursue the comprehensive cell autonomous and cell non-autonomous characterization of this chemoresistant AML disease using whole-exome and ChIP-sequencing. To establish a mutationally-induced chemoresistant mouse model, I will conduct an innovative in vivo screen using pooled mutant open reading frame and shRNA libraries in order to predict which combinations of mutations, among those already known in AML, actively promote chemoresistance. Finally, by combining genomic profiling and in vivo shRNA screening experiments, I will decipher the molecular mechanisms and identify the functional effectors of these two modes of resistance. Ultimately, I will then be able to firmly establish the fundamental relevance of the stochastic and/or the mutational model of chemoresistance for MRD genesis.

1 500 000 €

Start date: 2018-03-01, End date: 2023-02-28

From medieval times, Arabic as well as European music was analysed in terms that were inherited from Classical Antiquity and had thus developed in a very different music culture. In spite of recent breakthroughs in the understanding of the latter, whose technicalities we access not only through texts and iconography, but also through instrument finds and surviving notated melodies, its relation to music traditions known from later periods and different places is almost uncharted territory. The present project explores relations between Hellenic/Hellenistic music as pervaded the theatres and concert halls throughout and beyond the Roman empire, Near Eastern traditions – from the diatonic system emerging from cuneiform sources to the flourishing musical world of the caliphates – and, as far as possible, African musical life south of Egypt as well – a region that maintained close ties both with the Hellenised culture of its northern neighbours and with the Arabian Peninsula. On the one hand, this demands collaboration between Classical Philology and Arabic Studies, extending methods recently developed within music archaeological research related to the Classical Mediterranean. Arabic writings need to be examined in close reading, using recent insights into the interplay between ancient music theory and practice, in order to segregate the influence of Greek thinking from ideas and facts that must relate to contemporaneous ‘Arabic’ music-making. In this way we hope better to define the relation of this tradition to the ‘Classical world’, potentially breaking free of Orientalising bias informing modern views. On the other hand, the study and reconstruction, virtual and material, of wind instruments of Hellenistic pedigree but found outside the confinements of the Hellenistic ‘heartlands’ may provide evidence of ‘foreign’ tonality employed in those regions – specifically the royal city of Meroë in modern Sudan and the Oxus Temple in modern Tajikistan.

775 959 €

Start date: 2018-09-01, End date: 2023-08-31

Angiogenesis research has focused on the sprouting of new capillaries. The mechanisms of vessel maturation are much less well understood. Yet, the maintenance of a mature, quiescent, and organotypically-differentiated layer of endothelial cells (ECs) lining the inside of all blood vessels is vital for human health. The goal of ANGIOMATURE is to identify, validate, and implement novel mechanisms of vascular maturation and organotypic EC differentiation that are active during development, maintenance of vascular stability in adults, and undergo changes in aging. We recently identified previously unrecognized gene expression signatures of vascular maturation in a genome-wide screen of ECs isolated from newborn and adult mice. Epigenetic mechanisms were identified that control the EC transcriptome through gain and loss of DNA methylation as well as EC differentiation and signaling specification. These findings pave the way for groundbreaking novel opportunities to study vascular maturation. By characterizing functionally diverse types of blood vessels, including continuous ECs in lung and brain and sinusoidal ECs in liver and bone marrow, the ANGIOMATURE project will (1) determine up to single cell resolution the transcriptional and epigenetic program(s) of vascular maturation and organotypic differentiation during adolescence, (2) analyze the functional consequences of such program(s) in differentiated ECs and their adaptation to challenge, and (3) study changes of maturation and differentiation program(s) and vascular responses during aging. We will towards this end employ an interdisciplinary matrix of approaches involving omics, systems biology, conditional gene targeting, organoid cell culture, and experimental pathology to create a high-resolution structural and functional organotypic angioarchitectural map. The project will thereby yield transformative mechanistic insights into vital biological processes that are most important for human health and healthy aging.

2 338 918 €

Start date: 2018-08-01, End date: 2023-07-31

This proposal proceeds from an anomaly. Apartheid routinely breached the separation that it names. Whereas the South African regime was deeply isolationist in international terms, new research links it to the Cold War and decolonization. Yet this trend does not consider sufficiently that the global contest over the meaning of apartheid and resistance to it occurs on the terrain of culture. My project argues that studying the global circulation of South African cultural formations in the apartheid era provides novel historiographic leverage over Western liberalism during the Cold War. It recasts apartheid as an apparatus of transnational cultural production, turning existing historiography inside out. This study seeks: • To provide the first systematic account of the deterritorialization of “apartheid”—as political signifier and as apparatus generating circuits of transnational cultural production. • To analyze these itinerant cultural formations across media and national borders, articulating new intersections. • To map the itineraries of major South African exiles, where exile is taken to be a system of interlinked circuits of affiliation and cultural production. • To revise the historiography of states other than South Africa through the lens of deterritorialized apartheid-era formations at their respective destinations. • To show how apartheid reveals contradictions within Western liberalism during the Cold War, with special reference to racial inequality. Methodologically, I introduce the model of thick convergence to analyze three periods: 1. Kliptown & Bandung: Novel possibilities, 1948-1960. 2. Sharpeville & Memphis: Drumming up resistance, 1960-1976. 3. From Soweto to Berlin: Spectacle at the barricades, 1976-1990. Each explores a cultural dominant in the form of texts, soundscapes or photographs. My work stands at the frontier of transnational research, furnishing powerful new insights into why South Africa matters on the stage of global history.

1 861 238 €

Start date: 2014-05-01, End date: 2019-04-30

This proposal aims to unravel mysteries at the frontier of number theory and other areas of mathematics and physics. The main focus will be to understand and exploit “modularity” of q-hypergeometric series. “Modular forms are functions on the complex plane that are inordinately symmetric.” (Mazur) The motivation comes from the wide-reaching applications of modularity in combinatorics, percolation, Lie theory, and physics (black holes). The interplay between automorphic forms, q-series, and other areas of mathematics and physics is often two-sided. On the one hand, the other areas provide interesting examples of automorphic objects and predict their behavior. Sometimes these even motivate new classes of automorphic objects which have not been previously studied. On the other hand, knowing that certain generating functions are modular gives one access to deep theoretical tools to prove results in other areas. “Mathematics is a language, and we need that language to understand the physics of our universe.”(Ooguri) Understanding this interplay has attracted attention of researchers from a variety of areas. However, proofs of modularity of q-hypergeometric series currently fall far short of a comprehensive theory to describe the interplay between them and automorphic forms. A recent conjecture of W. Nahm relates the modularity of such series to K-theory. In this proposal I aim to fill this gap and provide a better understanding of this interplay by building a general structural framework enveloping these q-series. For this I will employ new kinds of automorphic objects and embed the functions of interest into bigger families A successful outcome of the proposed research will open further horizons and also answer open questions, even those in other areas which were not addressed in this proposal; for example the new theory could be applied to better understand Donaldson invariants.

1 240 500 €

Start date: 2014-01-01, End date: 2019-04-30

Dante Alighieri at the dawn of the 1300s, as well as Eustache Deschamps almost a century later, conceived poetry as music in itself. But what happens with poetry when it is involved in the complex architecture of polyphony? The aim of this project is to study for the first time the corpus of 14th- and early 15th-century poetry set to music by Ars Nova polyphonists (more than 1200 texts). This repertoire gathers different poetic and musical traditions, as shown by the multilingual anthologies copied during the last years of the Schism. The choice of this corpus is motivated by two primary goals: a) to offer a new interpretation of its meaning and function in the cultural and historical context, one that may be then applied to the rest of coeval European lyric poetry; b) to overcome current disciplinary divisions in order to generate a new methodological balance between the project’s two main fields of interest (Comparative Literature / Musicology). Most Ars Nova polyphonists were directly associated with religious institutions. In many texts, the language of courtly love expresses the values of caritas, the theological virtue that guides wise rulers and leads them to desire the common good. Thus, the poetic figure of the lover becomes a metaphor for the political man, and love poetry can be used as a device for diplomacy, as well as for personal and institutional propaganda. From this unprecedented point of view, the project will develop three research lines in response to the following questions: 1) How is the relationship between poetry and music, and how is the dialogue between the different poetic and musical traditions viewed in relation to each context of production? 2) To what extent does Ars Nova poetry take part in the ‘soft power’ strategies exercised by the entire European political class of the time? 3) Is there a connection between the multilingualism of the manuscript tradition and the perception of the Ars Nova as a European, intercultural repertoire?

2 193 375 €

Start date: 2019-01-01, End date: 2023-12-31

The Arctic Ocean is a vast expanse of sea ice. Most of it is snow covered as are large continental regions for about half of the year. However, Global Change is arguably greatest in the Arctic, where temperatures have risen more than anywhere else in the last few decades. New record lows occurred in snow extent in June 2012 and sea ice extent in September 2012. Many observations show that widespread and sustained change is occurring in the Arctic driving this unique environmental system into a new state. This project focuses on the biogeochemical links between sea ice and snow and the composition and chemistry of the troposphere (the lowest ~10km of the atmosphere). This is an important topic because the concentrations of greenhouse gases and aerosol particles, which scatter sunlight directly and influence cloud properties, play key roles for our climate. Additionally, changes in the composition of the troposphere also affect the so-called oxidation capacity, the capability of the atmosphere to cleanse itself from pollutants. This project aims to deliver a step change improvement in our quantitative understanding of chemical exchanges between ocean, sea ice, snow and the atmosphere in polar regions, especially the Arctic and of Arctic tropospheric chemistry. Answering these fundamental questions is essential to predict future change in the Arctic and globally. To this end a unique sea ice chamber will be constructed in the laboratory and used to quantify exchange processes in sea ice. Furthermore a hierarchy of numerical models will be used, operating at different spatial and temporal scales and degree of process description from a very detailed 1D to a global Earth System model. This will allow a breakthrough in our understanding of the importance of the changes for the composition and oxidation capacity of the atmosphere and climate and will allow us to calculate adjusted Greenhouse Warming Potentials that include these processes.

1 192 911 €

Start date: 2014-05-01, End date: 2016-09-30

Autism spectrum disorders (ASD) affect 1-2% of the population and are a major public health issue. Heterogeneity between affected ASD individuals is substantial both at clinical and etiological levels, thus warranting the idea that we should begin characterizing the ASD population as multiple kinds of ‘autisms’. Without an advanced understanding of how heterogeneity manifests in ASD, it is likely that we will not make pronounced progress towards translational research goals that can have real impact on patient’s lives. This research program is focused on decomposing heterogeneity in ASD at multiple levels of analysis. Using multiple ‘big data’ resources that are both ‘broad’ (large sample size) and ‘deep’ (multiple levels of analysis measured within each individual), I will examine how known variables such as sex, early language development, early social preferences, and early intervention treatment response may be important stratification variables that differentiate ASD subgroups at phenotypic, neural systems/circuits, and genomic levels of analysis. In addition to examining known stratification variables, this research program will engage in data-driven discovery via application of advanced unsupervised computational techniques that can highlight novel multivariate distinctions in the data that signal important ASD subgroups. These data-driven approaches may hold promise for discovering novel ASD subgroups at biological and phenotypic levels of analysis that may be valuable for prioritization in future work developing personalized assessment, monitoring, and treatment strategies for subsets of the ASD population. By enhancing the precision of our understanding about multiple subtypes of ASD this work will help accelerate progress towards the ideals of personalized medicine and help to reduce the burden of ASD on individuals, families, and society.

1 499 444 €

Start date: 2018-01-01, End date: 2022-12-31

Fluids play an important role in fault zone and in earthquakes generation. Fluid pressure reduces the normal effective stress, lowering the frictional strength of the fault, potentially triggering earthquake ruptures. Fluid injection induced earthquakes (FIE) are direct evidence of the effect of fluid pressure on the fault strength. In addition, natural earthquake sequences are often associated with high fluid pressures at seismogenic depths. Although simple in theory, the mechanisms that govern the nucleation, propagation and recurrence of FIEs are poorly constrained, and our ability to assess the seismic hazard that is associated with natural and induced events remains limited. This project aims to enhance our knowledge of FIE mechanisms over entire seismic cycles through multidisciplinary approaches, including the following: - Set-up and installation of a new and unique rock friction apparatus that is dedicated to the study of FIEs. - Low strain rate friction experiments (coupled with electrical conductivity measurements) to investigate the influence of fluids on fault creep and earthquake recurrence. - Intermediate strain rate friction experiments to investigate the effect of fluids on fault stability during earthquake nucleation. - High strain rate friction experiments to investigate the effect of fluids on fault weakening during earthquake propagation. - Post-mortem experimental fault analyses with state-of-art microstructural techniques. - The theoretical friction law will be calibrated with friction experiments and faulted rock microstructural observations. These steps will produce fundamental discoveries regarding natural earthquakes and tectonic processes and help scientists understand and eventually manage the occurrence of induced seismicity, an increasingly hot topic in geo-engineering. The sustainable exploitation of geo-resources is a key research and technology challenge at the European scale, with a substantial economical and societal impact.

1 982 925 €

Start date: 2018-03-01, End date: 2023-12-31

"I will study questions of central microeconomic importance via interwoven theoretical, empirical, and experimental analyses, from a behavioural perspective combining standard methods with assumptions that better reflect evidence on behaviour and psychological insights. The contributions of behavioural economics have been widely recognized, but the benefits of its insights are far from fully realized. I propose four lines of inquiry that focus on how institutions interact with cognition and behaviour, chosen for their potential to reshape our understanding of important questions and their synergies across lines. The first line will study nonparametric identification and estimation of reference-dependent versions of the standard microeconomic model of consumer demand or labour supply, the subject of hundreds of empirical studies and perhaps the single most important model in microeconomics. It will allow such studies to consider relevant behavioural factors without imposing structural assumptions as in previous work. The second line will analyze history-dependent learning in financial crises theoretically and experimentally, with the goal of quantifying how market structure influences the likelihood of a crisis. The third line will study strategic thinking experimentally, using a powerful new design that links subjects’ searches for hidden payoff information (“eye-movements”) much more directly to thinking. The fourth line will significantly advance Myerson and Satterthwaite’s analyses of optimal design of bargaining rules and auctions, which first went beyond the analysis of given institutions to study what is possible by designing new institutions, replacing their equilibrium assumption with a nonequilibrium model that is well supported by experiments. The synergies among these four lines’ theoretical analyses, empirical methods, and data analyses will accelerate progress on each line well beyond what would be possible in a piecemeal approach."

1 985 373 €

Start date: 2014-04-01, End date: 2019-03-31

What makes for a valuable and good life is a question that many people in the contemporary world ask themselves, yet it is one that social science research has seldom addressed. Only recently have scholars started undertaking inductive comparative research on different notions of the ‘good life’, highlighting socio-cultural variations and calling for a better understanding of the different imaginaries, aspirations and values that guide people in their quest for better living conditions. Research is still lacking, however, on how people themselves evaluate, compare, and put into perspective different visions of good living and their socio-cultural anchorage. This project addresses such questions from an anthropological perspective, proposing an innovative study of how ideals of the good life are articulated, (re)assessed, and related to specific places and contexts as a result of the experience of crisis and migration. The case studies chosen to operationalize these lines of enquiry focus on the phenomenon of return migration, and consist in an analysis of the imaginaries and experience of return by Ecuadorian and Cuban men and women who migrated to Spain, are dissatisfied with their life there, and envisage/carry out the project of going back to their countries of origin (Ecuador and Cuba respectively). The project’s ambition is to bring together and contribute to three main scholarly areas of enquiry: 1) the study of morality, ethics and what counts as ‘good life’, 2) the study of the field of economic practice, its definition, value regimes, and ‘crises’, and 3) the study of migratory aspirations, projects, and trajectories. A multi-sited endeavour, the research is designed in three subprojects carried out in Spain (PhD student), Ecuador (Post-Doc), and Cuba (PI), in which ethnographic methods will be used to provide the first empirically grounded study of the links between notions and experiences of crisis, return migration, and the (re)assessment of good living.

1 500 000 €

Start date: 2018-02-01, End date: 2023-07-31

This project investigates the cross-fertilisation of Anglo/American and German literature and film during the Allied Occupation of Germany. It will be the first study to survey the cultural landscape of the British and American zones of Occupied Germany in any detail. By doing so it will offer a new interpretative framework for postwar culture, in particular in three areas: the history of the Allied Occupation of Germany; the history of postwar Anglophone and Germanophone literature (arguing the two were more intertwined than has previously been suggested); and the history of the relationship between postwar and Cold War. Combining Anglo-American and German literature and film history with critical analysis, cultural history and life-writing, this is a necessarily ambitious, multidisciplinary study which will open up a major new field of research.

1 414 601 €

Start date: 2013-09-01, End date: 2019-02-28

According to the European Commission, to design effective policies for ensuring a “more dynamic, innovative and competitive” economy, it is essential to understand the decision-making process of firms as they differ a lot in terms of their capacities and policy responses (EC 2007). The objective of my future research is to provide such an analysis. BIGlobal will examine the sources of firm growth and market power to provide new insights into welfare and policy in a globalized world. Much of analysis of the global economy is set in the paradigm of markets that allocate resources efficiently and there is little role for policy. But big firms dominate economic activity, especially across borders. How do firms grow and what is the effect of their market power on the welfare impact of globalization? This project will determine how firm decisions matter for the aggregate gains from globalization, the division of these gains across different individuals and their implications for policy design. Over the next five years, I will incorporate richer firms behaviour in models of international trade to understand how trade and industrial policies impact the growth process, especially in less developed markets. The specific questions I will address include: how can trade and competition policy ensure consumers benefit from globalization when firms engaged in international trade have market power, how do domestic policies to encourage agribusiness firms affect the extent to which small farmers gain from trade, how do industrial policies affect firm growth through input linkages, and what is the impact of banking globalization on the growth of firms in the real sector. Each project will combine theoretical work with rich data from developing economies to expand the frontier of knowledge on trade and industrial policy, and to provide a basis for informed policymaking.

1 313 103 €

Start date: 2017-12-01, End date: 2022-11-30

Protein nanopatterning concerns the geometric arrangement of individual proteins with nanometre accuracy. It is becoming apparent that protein nanopatterns are essential for cellular function, and have roles in cell signalling and protection, phagocytosis and stem cell differentiation. Recent research indicates that our immune system is activated by nanopatterned antibody platforms, which initiate the classical Complement pathway by binding to the first component of Complement, the C1 complex. DNA nanotechnology can be used to form self-assembled nanoscale structures, which are ideal for use as templates to pattern proteins with specific geometries and nanometre accuracy. I propose to use DNA to nanopattern antigens and agonistic aptamers with defined geometry to study and control Complement pathway activation by the C1 complex. To develop and demonstrate the potential use of DNA to nanopattern proteins, the first aim of this proposal is to design DNA nanotemplates suitable for patterning antibody-binding sites. Antibodies and C1 will bind with specific geometry, and the relationship between antibody geometry and Complement activation will be assessed using novel liposome assays. Using DNA to mimic antigenic surfaces will enable high-resolution structure determination of DNA-antibody-C1 complexes, both in solution and on lipid bilayer surfaces, using phase plate cryo-electron microscopy to elucidate the structure-activation relationship of C1. The second aim of this proposal is to evolve agonistic aptamers that directly bind to and activate C1, and incorporate these into DNA nanotemplates. These nanopatterned aptamers will enable further study of C1 activation, and allow direct targeting of Complement activation to specific cells within a population of cell types to demonstrate targeted cell killing. This may open up new and highly efficient ways to activate our immune system in vivo, with potential for targeted anti-tumour immunotherapies.

1 499 850 €

Start date: 2018-01-01, End date: 2022-12-31

"Atmospheric aerosol particles have been shown to impact the earth's climate because they scatter and absorb solar radiation (direct effect) and because they can modify the microphysical properties of clouds by acting as cloud condensation nuclei or ice nuclei (indirect effects). Radiative forcing by anthropogenic aerosols remains poorly quantified, thus leading to considerable uncertainty in our understanding of the earth’s climate response to the radiative forcing by greenhouse gases. Black carbon (BC), mostly emitted by anthropogenic combustion processes and biomass burning, is an important component of atmospheric aerosols. Estimates show that BC may be the second strongest contributor (after CO2) to global warming. Adverse health effects due to particulate air pollution have also been associated with traffic-related BC particles. These climate and health effects brought BC emission reductions into the political focus of possible mitigation strategies with immediate and multiple benefits for human well-being. Laboratory experiments aim at the physical and chemical characterisation of BC emissions from diesel engines and biomass burning under controlled conditions. A mobile laboratory equipped with state-of-the-art aerosol sensors will be used to determine the contribution of different BC sources to atmospheric BC loadings, and to investigate the evolution of the relevant BC properties with atmospheric aging during transport from sources to remote areas. The interactions of BC particles with clouds as a function of BC properties will be investigated with in-situ measurements by operating quantitative single particle instruments behind a novel sampling inlet, which makes selective sampling of interstitial, cloud droplet residual or ice crystal residual particles possible. Above experimental studies aim at improving our understanding of BC’s atmospheric life cycle and will be used in model simulations for quantitatively assessing the atmospheric impacts of BC."

1 992 015 €

Start date: 2014-03-01, End date: 2019-02-28

Blood and bone are closely intertwined. Their intrinsic regenerative capacities are disturbed in many hematological and musculoskeletal diseases. Re-establishing the regenerative potential is the key to cure these diseases by regenerative medicine. Multipotent stem cells of both tissues – hematopoietic stem cells (HSCs) for blood and mesenchymal stem/stromal (MSCs) for bone – are the basis for their regenerative capacity. While it is well established that HSCs are influenced by the bone marrow in their natural environment including MSCs and their progeny, surprisingly little attention has been paid to the reciprocal relationship. The hypothesis of the current proposal is that only when taking both tissues and their mutual crosstalk into account, we will be able to understand how the regenerative potential of blood and bone is impaired in disease and how it can be re-established with novel treatment strategies. For this purpose we need to understand the early events of disease onset and progression. Due to the limitations of such studies in human beings and animals, I propose to develop human in vitro models of healthy bone marrow, which can be induced to develop hematological and musculoskeletal diseases with high incidence, namely leukemia, multiple myeloma and bone metastasis. Previously my team and I developed a simplified bone marrow analog that bases on macroporous, cell-laden biomaterials with tunable physical, biochemical and biological properties. This versatility will enable us to create biomimetic human in vitro models of the human bone marrow in health and disease, which are ground-breaking in their applicability to investigate how the regenerative balance of bone marrow is maintained in health and disturbed in the different kinds of diseases – a prerequisite to develop novel regenerative treatments – as well as their scalability and thus suitability as in vitro test systems for screening of novel drugs or treatments.

1 499 920 €

Start date: 2018-02-01, End date: 2023-12-31

Parkinson’s Disease is usually characterised by motor impairment, and Autism by social difficulties. However, the co-occurrence of social and motor symptoms is critically underappreciated; Parkinson’s Disease patients exhibit social symptoms, and motor difficulties are common in Autism. At present, the biological basis of co-occurring social and motor impairment is unclear. Notably, both Autism and Parkinson’s Disease have been associated with dopamine (DA) system dysfunction and, in non-clinical populations, DA has been linked with social and motor ability. These disparate strands of research have never been combined. Brain2Bee will use psychopharmacology in typical individuals to develop a model of the relationship between DA, Motor, and Social behaviour – the DAMS model. Brain2Bee will use sophisticated genetic analysis to refine DAMS, elucidating the contributions of DA-related biological processes (e.g. synthesis, receptor expression, reuptake). Brain2Bee will then test DAMS’ predictions in patients with Parkinson’s Disease and Autism. Finally, Brain2Bee will investigate whether DAMS generalises to an animal model, the honey bee, enabling future research to unpack the cascade of biological events linking DA-related genes with social and motor behaviour. Brain2Bee will unite disparate research fields and establish the DAMS model. The causal structure of DAMS will identify the impact of dopaminergic variation on social and motor function in clinical and non-clinical populations, elucidating, for example, whether social difficulties in Parkinson’s Disease are a product of the motor difficulties caused by DA dysfunction. DAMS’ biological specificity will provide unique insight into the DA-related processes linking social and motor difficulties in Autism. Thus, Brain2Bee will determine the type of dopaminergic drugs (e.g. receptor blockers, reuptake inhibitors) most likely to improve both social and motor function.

1 783 147 €

Start date: 2018-07-01, End date: 2023-06-30

"Conscious experiences normally result from the flow of external input into our sensory systems. However, our minds are also able to create conscious percepts in the absence of any sensory stimulation; these internally generated percepts are referred to as mental images, and they have many similarities with real visual percepts; consequently, mental imagery is often referred to as “seeing in the mind’s eye”. Mental imagery is also believed to be closely related to working memory, a mechanism which can maintain “offline” representations of visual stimuli no longer in the observer’s view, as both involve internal representations of previously seen visual attributes. Indeed, visual imagery is often thought of as a conscious window into the content of memory representations. Imagery, working memory, and conscious perception are thus thought to rely on very similar mechanisms. However, in everyday life we are generally able to keep apart the constructs of our imagination from real physical events; this begs the question of how the brain distinguishes internal mental images from externally induced visual percepts. To answer this question, the proposed work aims to isolate the cortical mechanisms associated uniquely with WM and imagery independently of each other and independently of the influence of external conscious percepts. Furthermore, by the use of neuroimaging and brain stimulation, we aim to determine the cortical mechanisms which keep apart internally generated and externally induced percepts, in both health and disease. This is a question of great clinical interest, as the ability to distinguish the perceived from the imagined is impoverished in psychotic disorders. In addition to revealing the mechanisms underlying this confusion, the present project aims to alleviate it in psychotic patients by the use of brain stimulation. The project will thus significantly improve our understanding of these cognitive processes and will also have clinical implications."

1 280 680 €

Start date: 2014-02-01, End date: 2019-01-31

"The proposed research project seeks to further our understanding on two important questions for the design of monetary policy: (a) What are the effects of monetary policy interventions on asset price bubbles? (b) How should monetary policy be conducted in the presence of asset price bubbles? The first part of the project will focus on the development of a theoretical framework that can be used to analyze rigorously the implications of alternative monetary policy rules in the presence of asset price bubbles, and to characterize the optimal monetary policy. In particular, I plan to use such a framework to assess the merits of a “leaning against the wind” strategy, which calls for a systematic rise in interest rates in response to the development of a bubble. The second part of the project will seek to produce evidence, both empirical and experimental, regarding the effects of monetary policy on asset price bubbles. The empirical evidence will seek to identify and estimate the sign and response of asset price bubbles to interest rate changes, exploiting the potential differences in the joint behavior of interest rates and asset prices during “bubbly” episodes, in comparison to “normal” times. In addition, I plan to conduct some lab experiments in order to shed some light on the link between monetary policy and bubbles. Participants will trade two assets, a one-period riskless asset and a long-lived stock, in an environment consistent with the existence of asset price bubbles in equilibrium. Monetary policy interventions will take the form of changes in the short-term interest rate, engineered by the experimenter. The experiments will allow us to evaluate some of the predictions of the theoretical models regarding the impact of monetary policy on the dynamics of bubbles, as well as the effectiveness of “leaning against the wind” policies."

799 200 €

Start date: 2014-01-01, End date: 2017-12-31

The actual view of cellular transformation and cancer progression supports the notion that cancer cells must undergo metabolic reprogramming in order to survive in a hostile environment. This field has experienced a renaissance in recent years, with the discovery of cancer genes regulating metabolic homeostasis, in turn being accepted as an emergent hallmark of cancer. Prostate cancer presents one of the highest incidences in men mostly in developed societies and exhibits a significant association with lifestyle environmental factors. Prostate cancer recurrence is thought to rely on a subpopulation of cancer cells with low-androgen requirements, high self-renewal potential and multidrug resistance, defined as cancer-initiating cells. However, whether this cancer cell fraction presents genuine metabolic properties that can be therapeutically relevant remains undefined. In CancerMetab, we aim to understand the potential benefit of monitoring and manipulating metabolism for prostate cancer prevention, detection and therapy. My group will carry out a multidisciplinary strategy, comprising cellular systems, genetic mouse models of prostate cancer, human epidemiological and clinical studies and bioinformatic analysis. The singularity of this proposal stems from the approach to the three key aspects that we propose to study. For prostate cancer prevention, we will use our faithful mouse model of prostate cancer to shed light on the contribution of obesity to prostate cancer. For prostate cancer detection, we will overcome the consistency issues of previously reported metabolic biomarkers by adding robustness to the human studies with mouse data integration. For prostate cancer therapy, we will focus on a cell population for which the metabolic requirements and the potential of targeting them for therapy have been overlooked to date, that is the prostate cancer-initiating cell compartment.

1 498 686 €

Start date: 2013-11-01, End date: 2019-10-31

"We want to determine how oxidants are sensed and transduced into a biological effect within the cardiovascular system. The proposed work will focus on thiol-based redox sensors, defining their role in heart and blood vessel function during health and disease. Although this laboratory has studied the molecular basis of redox signaling for more than a decade, the subject is still in its relative infancy with considerable scope for major advances. Oxidant signaling remains a ‘hot topic’ with high profile studies confirming a fundamental role for redox control of protein and cellular function continuing to emerge. The molecular basis of redox sensing is the reaction of an oxidant with target proteins. This gives rise to oxidative post-translational modifications, most commonly of cysteinyl thiols, potentially altering the activity of proteins to regulate cell or tissue function. One of the reasons there are so many unanswered questions about redox sensing and signaling is the diversity of oxidant molecules produced by cells that can interact with sensor proteins to alter their function. This application is aimed at extending our knowledge of redox sensing and signalling, allowing us to define its importance in cardiovascular health and disease."

2 255 659 €

Start date: 2013-12-01, End date: 2018-11-30

According to string theory, coherent sheaves on three-dimensional Calabi-Yau spaces encode fundamental properties of the universe. On the other hand, they have a purely mathematical definition. We will develop and use the new field of categorified Donaldson-Thomas (DT) theory, which counts these objects. Via the powerful perspective of noncommutative algebraic geometry, this theory has found application in recent years in a wide variety of contexts, far from classical algebraic geometry. Categorification has proved tremendously powerful across mathematics, for example the entire subject of algebraic topology was started by the categorification of Betti numbers. The categorification of DT theory leads to the replacement of the numbers of DT theory by vector spaces, of which these numbers are the dimensions. In the area of categorified DT theory we have been able to prove fundamental conjectures upgrading the famous wall crossing formula and integrality conjecture in noncommutative algebraic geometry. The first three projects involve applications of the resulting new subject: 1. Complete the categorification of quantum cluster algebras, proving the strong positivity conjecture. 2. Use cohomological DT theory to prove the outstanding conjectures in the nonabelian Hodge theory of Riemann surfaces, and the subject of Higgs bundles. 3. Prove the comparison conjecture, realising the study of Yangian quantum groups and the geometric representation theory around them as a special case of DT theory. The final objective involves coming full circle, and applying our recent advances in noncommutative DT theory to the original theory that united string theory with algebraic geometry: 4. Develop a generalised theory of categorified DT theory extending our results in noncommutative DT theory, proving the integrality conjecture for categories of coherent sheaves on Calabi-Yau 3-folds.

1 239 435 €

Start date: 2017-11-01, End date: 2023-04-30

Understanding cause-effect relationships between variables is of great interest in many fields of science. However, causal inference from data is much more ambitious and difficult than inferring (undirected) measures of association such as correlations, partial correlations or multivariate regression coefficients, mainly because of fundamental identifiability problems. A main objective of the proposal is to exploit advantages from large-scale heterogeneous data for causal inference where heterogeneity arises from different experimental conditions or different unknown sub-populations. A key idea is to consider invariance or stability across different experimental conditions of certain conditional probability distributions: the invariants correspond on the one hand to (properly defined) causal variables which are of main interest in causality; andon the other hand, they correspond to the features for constructing powerful predictions for new scenarios which are unobserved in the data (new probability distributions). This opens novel perspectives: causal inference can be phrased as a prediction problem of a certain kind, and vice versa, new prediction methods which work well across different scenarios (unobserved in the data) should be based on or regularized towards causal variables. Fundamental identifiability limits will become weaker with increased degree of heterogeneity, as we expect in large-scale data. The topic is essentially unexplored, yet it opens new avenues for causal inference, structural equation and graphical modeling, and robust prediction based on large-scale complex data. We will develop mathematical theory, statistical methodology and efficient algorithms; and we will also work and collaborate on major application problems such as inferring causal effects (i.e., total intervention effects) from gene knock-out or RNA interference perturbation experiments, genome-wide association studies and novel prediction tasks in economics.

2 184 375 €

Start date: 2018-10-01, End date: 2023-09-30

"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."

2 469 268 €

Start date: 2014-02-01, End date: 2019-01-31

Sphingolipids including ceramides are building blocks of cell membranes, but also act as regulated intracellular messenger molecules. Emerging data indicate that sphingolipids are dynamically regulated by nutrients, and in turn control systemic metabolism, for example, by modulating insulin secretion, proliferation and cell death of pancreatic beta cells. Dysfunction and death of beta cells are key events during the development of diabetes, from which more than 400 million patients suffer worldwide. While pharmacological inhibition of general ceramide biosynthesis is protective against diabetes in animal studies, side effects of total loss of ceramides prevent medical implementation. The de novo synthesis of ceramides is fully dependent on six ceramide synthase enzymes (CerS 1-6), which are expressed in a tissue specific manner, and generate ceramides with different chain lengths. Currently, the functional roles and regulatory modulators of each CerS are unknown in pancreatic beta cells. Importantly, the downstream mechanisms by which ceramides impair beta cell function and eventually cause diabetes are not defined. Here, I propose to combine genomics, proteomics and lipidomics to assess the function of ceramide synthases expressed in mouse and human beta cells. Furthermore, both the subcellular localisation and the post-translational modifications of CerS will be determined. The ceramide-interacting proteins mediating the deleterious effects of ceramides will be identified by lipid-protein crosslinking and functionally tested. Finally, in a translational approach, we will test the ability of recently generated novel specific CerS inhibitors with improved specificity to ameliorate beta cell stress, and improve insulin secretion in mouse and human beta cells. In sum, we will identify, characterize, validate and target ceramide synthases involved in beta cell biology and development of diabetes.

1 492 314 €

Start date: 2018-01-01, End date: 2022-12-31

With its emergence as a global power, China aspires to move from a “made in China” towards a “created in China” country. Creativity and culture have become a crucial source for innovation and financial growth, but are also mobilised to promote a new and open China to both the citizenry as well as the outside world. They are part of what is termed China’s “soft power.” What does creativity mean in the context of China, and what does it do? When both the state and profoundly globalised creative industries are so deeply implicated in the promotion of creativity, what are the possibilities of criticality, if any? Whereas creativity has been extensively researched in the fields of psychology, law and neurosciences, scholarship in the humanities has by and large side-tracked the thorny issue of creativity. Yet, the worldwide resurgence of the term under the banner of creative industries makes it all the more urgent to develop a theory of creativity. This project understands creativity as a textual, a social as well as a heritage practice. It aims to analyse claims of creativity in different cultural practices, and to analyse how emerging creativities in China are part of tactics of governmentality and disable or enable possibilities of criticality. Using a comparative, multi-disciplinary, multi-method and multi-sited research design, five subprojects analyse (1) contemporary art, (2) calligraphy, (3) independent documentary cinema, (4) television from Hunan Satellite TV and (5) “fake” (shanzhai) art. By including both popular and high arts, by including both more Westernized as well as more specifically Chinese art forms, by including both the “real” as well as the “fake,” by studying different localities, and by mobilising methods from both the social sciences and the humanities, this project is pushing the notion of comparative research to a new level.

1 947 448 €

Start date: 2014-09-01, End date: 2019-08-31

"The eruption of volcanoes appears one of the most unpredictable phenomena on Earth. Yet the situation is rapidly changing. Quantification of the eruptive record constrains what is possible in a given volcanic system. Timing is the hardest part to quantify. The main process triggering an eruption is the refilling of a sub-volcanic magma chamber by a new magma coming from depth. This process results in magma mixing and provokes a time-dependent diffusion of chemical elements. Understanding the time elapsed from mixing to eruption is fundamental to discerning pre-eruptive behaviour of volcanoes to mitigate the huge impact of volcanic eruptions on society and the environment. The CHRONOS project proposes a new method that will cut the Gordian knot of the presently intractable problem of volcanic eruption timing using a surgical approach integrating textural, geochemical and experimental data on magma mixing. I will use the compositional heterogeneity frozen in time in the rocks the same way a broken clock at a crime scene is used to determine the time of the incident. CHRONOS will aim to: 1) be the first study to reproduce magma mixing, by performing unique experiments constrained by natural data and using natural melts, under controlled rheological and fluid-dynamics conditions; 2) obtain unprecedented high-quality data on the time dependence of chemical exchanges during magma mixing; 3) derive empirical relationships linking the extent of chemical exchanges and the mixing timescales; 4) determine timescales of volcanic eruptions combining natural and experimental data. CHRONOS will open a new window on the physico-chemical processes occurring in the days preceding volcanic eruptions providing unprecedented information to build the first inventory of eruption timescales for planet Earth. If these timescales can be linked with geophysical signals occurring prior to eruptions, this inventory will have an immense value, enabling precise prediction of volcanic eruptions."

1 993 813 €

Start date: 2014-05-01, End date: 2019-04-30

The ubiquity of arsenic resistant genes across all of life’s variety suggests a close intimacy between arsenic biogeochemistry and evolution, over geological time scales. However, the behaviour of arsenic in past environments where life originated and its impact on our evolution is essentially unknown. Arsenic is of particular importance because of its toxic properties, prevalence in tight association with ubiquitous iron and sulfide minerals and as a major component of sulfide-rich waters, all common features of Precambrian oceans. Arsenic obstructs the synthesis of the building blocks of life, exhibiting both chronic and acute toxicity at very low concentrations. These properties make arsenic an agent capable of exerting strong selective pressure on the distribution, success and diversity of life. This is exemplified by when the release of arsenic into groundwater following rock-weathering processes results in widespread poisoning. Using the state of the art stable isotopes tools, coupled to biomass production, bacterial iron, arsenic and sulfur cycling under ancient oceanic conditions, this project will open a new discussion on the much debated relationship between ocean chemistry and evolution, by introducing a new arsenic framework. This will be achieved under three majors themes: 1) Does there exist a biogeochemical connection between arsenic and the timing and transition from the iron-rich to the hypothesized sulfide-rich oceans that are linked to the rise of atmospheric oxygen? 2) Does arsenic and sulfide show concomitant cyclicity during the Precambrian? 3) Could arsenic thus serve as a proxy for the calibration of key transitional steps in the timing of biological innovation?

1 486 374 €

Start date: 2013-09-01, End date: 2018-08-31

"This proposal connects three areas that are considered distant from each other: computational complexity, algebraic geometry, and numerics. In the last decade, it became clear that the fundamental questions of computational complexity (P vs NP) should be studied in algebraic settings, linking them to problems in algebraic geometry. Recent progress on this challenging and very difficult questions led to surprising progress in computational invariant theory, which we want to explore thoroughly. We expect this to lead to solutions of computational problems in invariant theory that currently are considered infeasible. The complexity of Hilbert's null cone (the set of ""singular objects'') appears of paramount importance here. These investigations will also shed new light on the foundational questions of algebraic complexity theory. As an essential new ingredient to achieve this, we will tackle the arising algebraic computational problems by means of approximate numeric computations, taking into account the concept of numerical condition. A related goal of the proposal is to develop a theory of efficient and numerically stable algorithms in algebraic geometry that reflects the properties of structured systems of polynomial equations, possibly with singularities. While there are various heuristics, a satisfactory theory so far only exists for unstructured systems over the complex numbers (recent solution of Smale's 17th problem), which seriously limits its range of applications. In this framework, the quality of numerical algorithms is gauged by a probabilistic analysis that shows small average (or smoothed) running time. One of the main challenges here consists of a probabilistic study of random structured polynomial systems. We will also develop and analyze numerical algorithms for finding or describing the set of real solutions, e.g., in terms of their homology. "

2 297 163 €

Start date: 2019-01-01, End date: 2023-12-31

All of us know of individuals who remain cognitively sharp at an advanced age. Identifying novel factors which associate with inter-individual variability in -and can be considered protective for- cognitive decline is a promising area in ageing research. Considering its strong implication in neuroprotective function, COGNAP predicts that variability in circadian rhythmicity explains a significant part of the age-related changes in human cognition. Circadian rhythms -one of the most fundamental processes of living organisms- are present throughout the nervous system and act on cognitive brain function. Circadian rhythms shape the temporal organization of sleep and wakefulness to achieve human diurnality, characterized by a consolidated bout of sleep during night-time and a continuous period of wakefulness during the day. Of prime importance is that the temporal organization of sleep and wakefulness evolves throughout the adult lifespan, leading to higher sleep-wake fragmentation with ageing. The increasing occurrence of daytime napping is the most visible manifestation of this fragmentation. Contrary to the common belief, napping stands as a health risk factor in seniors in epidemiological data. I posit that chronic napping in older people primarily reflects circadian disruption. Based on my preliminary findings, I predict that this disruption will lead to lower cognitive fitness. I further hypothesise that a re-stabilization of circadian sleep-wake organization through a nap prevention intervention will reduce age-related cognitive decline. Characterizing the link between cognitive ageing and the temporal distribution of sleep and wakefulness will not only bring ground-breaking advances at the scientific level, but is also timely in the ageing society. Cognitive decline, as well as inadequately timed sleep, represent dominant determinants of the health span of our fast ageing population and easy implementable intervention programs are urgently needed.

1 499 125 €

Start date: 2018-01-01, End date: 2023-06-30

Visual perception is central to how we think and behave. However, there are major unresolved issues in understanding how the human mind draws on experience to perceive the dynamic and variable world. The COLOURMIND project, led by Franklin, will tackle these crucial issues with an ambitious investigation of the impact of the visual environment on colour perception that will provide a new theoretical framework for the field. The project will ask ground-breaking questions: What aspects of colour perception are affected by the visual environment, such that people from different environments perceive colour differently?; What processes enable colour perception to calibrate to visual experience and what is their nature and scope?; Does colour perception ‘tune-in’ to the visual input experienced during infancy? COLOURMIND will adopt a diverse range of innovative methods to address these questions, and will: i.) investigate the colour perception of people immersed in natural non-industrialised environments in some of the remotest parts of the world to identify the extent to which visual environment shapes colour perception; ii.) use innovative neuroimaging methods to identify how the visual cortex changes in response to chromatic experience; iii.) pioneer the use of ‘Altered-Reality' (next generation virtual reality) to elucidate calibrative processes in colour perception; and iv.) conduct carefully controlled experiments with infants to address the role of development. The cutting-edge questions, innovative approaches and theoretical power of the COLOURMIND project will lead to breakthroughs on issues that are fundamental to understanding the complexity of the human mind (e.g., learning, plasticity and inference; perceptual development; cultural relativity), and findings will have practical application. Overall, the ambitious project will push the frontiers of multidisciplinary research on colour perception, and will resonate throughout the cognitive and social sciences.

1 999 975 €

Start date: 2018-07-01, End date: 2023-06-30

Targeted therapy (TT) is frequently used to treat metastatic cancer. Although TT can achieve effective tumor control for several months, durable treatment responses are rare, due to emergence of aggressive, drug-resistant clones (RCs) with high metastatic competence. Tumor heterogeneity and plasticity result in multifaceted resistance mechanisms and targeting RCs poses a daunting challenge. To better understand the clinical emergence of RCs, my work focuses on the poorly understood events during TT-induced tumor regression. We recently reported that during this phase drug-responsive cancer cells release a therapy-induced secretome, which remodels the tumor microenvironment (TME) and propagates disease relapse by promoting the survival of drug-sensitive cells and stimulating the outgrowth of RCs. Consequently, intervening with combination therapies during the tumor regression period has the potential to prevent the clinical emergence of RCs in the first place. Here, we outline strategies to (1) understand how RCs emerge and (2) to leverage our findings on the TME remodeling for combination therapies. First, we will develop a novel and innovative parental clone-lookup method, that will allow us to identify and isolate treatment-naïve, parental clones (PCs) that gave rise to RCs. In functional experiments, we will assess (i) whether PCs were already resistant before or developed resistance during TT, (ii) whether PCs have a higher susceptibility to develop resistance than random clones, and (iii) the mechanistic basis for metastatic competence in different clones. Second, we will study the TT-induced TME remodeling, focusing on the effects on tumor vasculature and immune cells. We will utilize our results to target PCs and RCs by combining TT in the phase of tumor regression with other therapies, such as immunotherapies. Our study will provide new mechanistic insights into the biological processes during tumor regression and aims for novel therapeutic strategies.

1 500 000 €

Start date: 2018-03-01, End date: 2023-02-28

Owing to their visual essence and status as a popular, modern medium, comics – newspaper strips, comics magazines and graphic novels – provide valuable insight into the transformation of collective consciousness. This project advances the hypothesis that children in comics are distinctive embodiments of the complex experience of modernity, channeling and tempering modern anxieties and incarnating the freedom denied to adults. In testing this hypothesis, the project constructs the first intercultural history of children in European comics, tracing the changing conceptualizations of child protagonists in popular comics for both children and adults from the mid-19th century to the present. In doing so, it takes key points in European history as well as the history of comics into account. Assembling a team of six multilingual researchers, the project uses an interdisciplinary methodology combining comics studies and childhood studies while also incorporating specific insights from cultural studies (history of family life, history of public life, history of the body, affect theory and scholarship on the carnivalesque). This enables the project to analyze the transposition of modern anxieties, conceptualizations of childishness, child-adult power relations, notions of liberty, visualizations of the body, family life, school and public life as well as the presence of affects such as nostalgia and happiness in comics starring children. The project thus opens up a new field of research lying at the intersection of comics studies and childhood studies and illustrates its potential. In studying popular but often overlooked comics, the project provides crucial historical and analytical material that will shape future comics criticism and the fields associated with childhood studies. Furthermore, the project’s outreach activities will increase collective knowledge about comic strips, which form an important, increasingly visible part of cultural heritage.

1 452 500 €

Start date: 2018-10-01, End date: 2023-09-30

This project focuses on nontrivial solutions of systems of differential equations characterized by strongly nonlinear interactions. We are interested in the effect of the nonlinearities on the emergence of non trivial self-organized structures. Such patterns correspond to selected solutions of the differential system possessing special symmetries or shadowing particular shapes. We want to understand, from the mathematical point of view, what are the main mechanisms involved in the aggregation process in terms of the global variational structure of the problem. Following this common thread, we deal with both with the classical N-body problem of Celestial Mechanics, where interactions feature attractive singularities, and competition-diffusion systems, where pattern formation is driven by strongly repulsive forces. More precisely, we are interested in periodic and bounded solutions, parabolic trajectories with the final intent to build complex motions and possibly obtain the symbolic dynamics for the general N–body problem. On the other hand, we deal with elliptic, parabolic and hyperbolic systems of differential equations with strongly competing interaction terms, modeling both the dynamics of competing populations (Lotka- Volterra systems) and other interesting physical phenomena, among which the phase segregation of solitary waves of Gross-Pitaevskii systems arising in the study of multicomponent Bose-Einstein condensates. In particular, we will study existence, multiplicity and asymptotic expansions of solutions when the competition parameter tends to infinity. We shall be concerned with optimal partition problems related to linear and nonlinear eigenvalues

1 346 145 €

Start date: 2014-02-01, End date: 2019-01-31

"The application proposes to revisit the economics of cooperation and competition in industry vertical chains and develop new tools for industrial organization (IO). Modern IO theory treats firms as unitary, profit-maximizing entities, characterized by well-identified perimeters of activity, and clearly identified either as competitors or as complementors. Yet in practice: - Industry structures are increasingly complex: Firms distribute for example their activities among partners across the globe, and moved to multiple, interlocking relationships. - Firms competing for customers or suppliers are also cooperating in other dimensions, e.g., by setting-up common platforms, or by adopting joint common rules within which to compete. - Supplier -customer relations often involve transaction costs other than pure search costs: adoption costs, learning or shopping costs, or expensive strategies to protect sensitive information. Understanding the interplay between competition and cooperation is key to designing business strategies, but it has also implications for industry oversight: When should cooperation among competitors be limited or encouraged? Over which dimensions? This application proposes to cover three topics: 1. Allocation of tasks and the choice of partners. 2. Multilateral interlocking relations. 3. Cooperation and competition. 4. Transaction costs, buying patterns and business strategies While the project falls primarily in the field of applied theory, some of the developments require new tools and interaction with game theorists. Furthermore, empirical validation will require the use of structural econometric modelling (based in particular on consumer panel data) and laboratory experiments. The project has also an interdisciplinary flavour and will benefit from work of and interactions with legal scholars and marketing experts."

2 068 920 €

Start date: 2013-12-01, End date: 2018-11-30

One of the main challenges in condensed matter physics is to understand strongly correlated quantum systems. Our purpose is to approach this issue from the point of view of rigorous mathematical analysis. The goals are twofold: develop a mathematical framework applicable to physically relevant scenarii, take inspiration from the physics to introduce new topics in mathematics. The scope of the proposal thus goes from physically oriented questions (theoretical description and modelization of physical systems) to analytical ones (rigorous derivation and analysis of reduced models) in several cases where strong correlations play the key role. In a first part, we aim at developing mathematical methods of general applicability to go beyond mean-field theory in different contexts. Our long-term goal is to forge new tools to attack important open problems in the field. Particular emphasis will be put on the structural properties of large quantum states as a general tool. A second part is concerned with so-called fractional quantum Hall states, host of the fractional quantum Hall effect. Despite the appealing structure of their built-in correlations, their mathematical study is in its infancy. They however constitute an excellent testing ground to develop ideas of possible wider applicability. In particular, we introduce and study a new class of many-body variational problems. In the third part we discuss so-called anyons, exotic quasi-particles thought to emerge as excitations of highly-correlated quantum systems. Their modelization gives rise to rather unusual, strongly interacting, many-body Hamiltonians with a topological content. Mathematical analysis will help us shed light on those, clarifying the characteristic properties that could ultimately be experimentally tested.

1 056 664 €

Start date: 2018-01-01, End date: 2022-12-31

Music performance is considered by many to be one of the most breath taking feats of human intelligence. That music performance is a creative act is no longer a disputed fact, but the very nature of this creative work remains illusive. Taking the view that the creative work of performance is the making and shaping of music structures, and that this creative thinking is a form of problem solving, COSMOS proposes an integrated programme of research to transform our understanding of the human experience of performed music, which is almost all music that we hear, and of the creativity of music performance, which addresses how music is made. The research themes are as follows: i) to find new ways to represent, explore, and talk about performance; ii) to harness volunteer thinking (citizen science) for music performance research by focussing on structures experienced and problem solving; iii) to create sandbox environments to experiment with making performed structures; iv) to create theoretical frameworks to discover the reasoning behind the structures perceived and made; and, v) to foster community engagement by training experts to provide feedback on structure solutions so as to increase public understanding of the creative work in music performance. Analysis of the perceived and designed structures will be based on a novel duality paradigm that turns conventional computational music structure analysis on its head to reverse engineer why a perceiver or a performer chooses a particular structure. Embedded in the approach is the use of computational thinking to optimise representations and theories to ensure accuracy, robustness, efficiency, and scalability. The PI is an established performer and a leading authority in music representation, music information research, and music perception and cognition. The project will have far reaching impact, reconfiguring expert and public views of music performance and time-varying music-like sequences such as cardiac arrhythmia.

2 495 776 €

Start date: 2019-06-01, End date: 2024-05-31

With COVOPRIM I propose to reconstruct the recent evolutionary history of one often overlooked component of speech and language: voice perception. Perceptual and neural mechanisms of voice perception will be compared between humans, macaques and marmosets –two highly vocal and extensively studied monkey species–to quantify cross-species differences and infer mechanisms potentially inherited from a common ancestor. Two key building blocks of vocal communication detailed in my past research in humans will be compared across species: (1) the sensitivity to conspecific vocalizations, and (2) the processing of speaker/caller identity. COVOPRIM is organized in three workpackages (WPs). WP1 will use large-scale behavioural testing based on ad-lib access of monkeys to automated test systems (following the highly successful model developed locally with baboons). Two main behavioural experiments will establish psychometric response functions for robust cross-species comparison. WP2 will use functional magnetic resonance imaging (fMRI) to measure cerebral activity during auditory stimulation in the three species. I will compare across brains the organization of what I hypothesize constitutes a “voice patch system” similar to the face patch system of visual cortex and broadly conserved in primates. I will also take advantage of the monkey models and use long-term, subject-specific enrichments of the auditory stimulation to probe the experience-dependence of neural coding in the voice patch system—an outstanding issue in human voice perception. WP3 will use fMRI-guided microstimulation in monkeys and transcranial magnetic stimulation in humans to establish the effective connectivity within the voice patch system and test the causal relation between voice patch neuronal activity and voice perception behaviour. COVOPRIM is expected to generate considerable advances in our understanding of the recent evolution in primates of the perceptual and neural mechanisms of voice perception.

2 900 000 €

Start date: 2019-01-01, End date: 2023-12-31

"This project aims to ""crack"" the emotional code of music, i.e. to provide, for the first time, a precise characterization of what type of music signal is able to activate one emotion or another. Research into this problem so far has been mainly correlating indistinct emotional reactions to uncontrolled musical stimuli, with much technical sophistication but to little avail. Project CREAM builds on the PI's unique bi-disciplinary career spanning both computer science and cognitive neuroscience, to propose a radically novel approach: instead of using audio signal processing to simply observe musical stimuli a posteriori, we will harvest a series of recent developments in the field to build powerful new tools of experimental control, able to engineer musical stimuli that can activate specific emotional pathways (e.g. music manipulated to sound like expressive speech, or to sound like survival-relevant environmental sounds). By combining this creative use of new technologies with a well-concerted mix of methods from experimental psychology and cognitive neuroscience (incl. psychoacoustics, fNIRS brain imaging, EEG/ERP paradigms, intercultural studies, infant studies), project CREAM will yield the first functional description of the neural and cognitive processes involved in the induction of emotions by music, and establish new avenues for interdisciplinary research between the life sciences and the information sciences. But most spectacularly, the fundamental breakthroughs brought by project CREAM will unlatch the therapeutic potential of musical emotions. Music will become a cognitive technology, with algorithms able to ""engineer"" it to mobilize one neuronal pathway or another, non-intrusively and non-pharmacologically. Within the proposed 5-year plan, support from the ERC will allow to implement a series of high-impact clinical studies with are direct applications of our findings, e.g. for the linguistic rehabilitation of aphasic stroke victims."

1 499 992 €

Start date: 2014-10-01, End date: 2019-09-30

"One of the main challenges of modern mathematical physics is to understand the behaviour of systems at or near criticality. In a number of cases, one can argue heuristically that this behaviour should be described by a nonlinear stochastic partial differential equation. Some examples of systems of interest are models of phase coexistence near the critical temperature, one-dimensional interface growth models, and models of absorption of a diffusing particle by random impurities. Unfortunately, the equations arising in all of these contexts are mathematically ill-posed. This is to the extent that they defeat not only ""standard"" stochastic PDE techniques (as developed by Da Prato / Zabczyk / Röckner / Walsh / Krylov / etc), but also more recent approaches based on Wick renormalisation of nonlinearities (Da Prato / Debussche / etc). Over the past year or so, I have been developing a theory of regularity structures that allows to give a rigorous mathematical interpretation to such equations, which therefore allows to build the mathematical objects conjectured to describe the abovementioned systems near criticality. The aim of the proposal is to study the convergence of a variety of concrete microscopic models to these limiting objects. The main fundamental mathematical tools to be developed in this endeavour are a discrete analogue to the theory of regularity structures, as well as a number of nonlinear invariance principles. If successful, the project will yield unique insight in the large-scale behaviour of a number of physically relevant systems in regimes where both nonlinear effects and random fluctuations compete with equal strength."

1 526 234 €

Start date: 2014-09-01, End date: 2019-08-31

Adaptive behaviour is typically attributed to an executive-control system that allows people to regulate impulsive actions and to fulfil long-term goals instead. Failures to regulate impulsive actions have been associated with a variety of clinical and behavioural disorders. Therefore, establishing a good understanding of impulse-control mechanisms and how to improve them could be hugely beneficial for both individuals and society at large. Yet many fundamental questions remain unanswered. This stems from a narrow focus on reactive inhibitory control and well-practiced actions. To make significant progress, we need to develop new models that integrate different aspects of impulsive action and executive control. The proposed research program aims to answer five fundamental questions. (1) Can novel impulsive actions arise during task-preparation stages?; (2) What is the role of negative emotions in the origin and control of impulsive actions?; (3) How does learning modulate impulsive behaviour?; (4) When are impulsive actions (dys)functional?; and (5) How is variation in state impulsivity associated with trait impulsivity? To answer these questions, we will use carefully designed behavioural paradigms, cognitive neuroscience techniques (TMS & EEG), physiological measures (e.g. facial EMG), and mathematical modelling of decision-making to specify the origin and control of impulsive actions. Our ultimate goal is to transform the impulsive action field by replacing the currently dominant ‘inhibitory control’ models of impulsive action with detailed multifaceted models that can explain impulsivity and control across time and space. Developing a new behavioural model of impulsive action will also contribute to a better understanding of the causes of individual differences in impulsivity and the many disorders associated with impulse-control deficits.

1 998 438 €

Start date: 2018-06-01, End date: 2023-11-30

The Inflammatory Bowel Diseases (IBD), Crohn’s Disease (CD) and Ulcerative Colitis (UC) are chronic/relapsing disorders that affect over six million individuals worldwide. Mucosal ulcers, the hallmark of CD, are the result of a complex interaction between microbiota, immune cells, and gut epithelia. Healing of mucosal ulcers is associated with better outcomes, but is achieved in less than half of cases. Past attempts to suppress central and conserved nodes of the immune system failed due to opposing off-target deleterious effects on epithelial renewal. Therefore, there is a critical need to identify more tissue specific targets that lead to mucosal healing and to improved outcomes. Using mRNAseq of intestinal biopsies, we identified a widespread dysregulation of long non-coding RNAs (lncRNA) in the ileum of treatment naïve pediatric CD patients. Importently, we identified significant correlations between lncRNA and mucosal ulcers. CD lncRNA, after carful mechanistic exploration, are highly promising targets for potential future intervention as they regulate diverse cellular functions and exhibit a more tissue specific expression in comparison to protein coding genes. The core goal of this proposal is to understand the role of CD lncRNA in ulcer pathogenesis focusing on granulocytes and epithelial functions in the contexts of their interactions with the microbiota. I plan to utilize state of the art informatics, RNAseq and microbiome profiles together with advanced and novel experimental lab model and co-culture systems, patients-derived prospectively collected tissues, and gut microbiota to explore the role of CD lncRNA function in mediating healing of mucosal ulcers. This work carries the potential to guide new novel therapeutic strategies for mucosal healing with minimal off-targets effects. In a broader prospective, this work will expand our relative limited understanding regarding the role of lncRNA in mediating human diseases.

1 500 000 €

Start date: 2018-05-01, End date: 2023-04-30

How did three soldiers override their initial freezing response to overpower an armed terrorist in the Thalys-train to Paris in 2015? This question is relevant for anyone aiming to optimize approach-avoidance (AA) decisions during threat. It is particularly relevant for patients with anxiety disorders whose persistent avoidance is key to the maintenance of their anxiety. Computational psychiatry has made great progress in formalizing how we make (mal)adaptive decisions. Current models, however, largely ignore the transient psychophysiological state of the decision maker. Parasympathetic state and flexibility in switching between para- and sympathetic states are directly related to freezing, and are known to bias AA-decisions toward avoidance. The central aim of this research program is to forge a mechanistic understanding of how we compute AA-decisions on the basis of those psychophysiological states, and to identify alterations in anxiety patients in order to guide new personalized neurocognitive interventions into their persistent avoidance. I will develop a neurocomputational model of AA-decisions that accounts for transient psychophysiological states, in order to define which decision parameters are altered in active and passive avoidance in anxiety. I will test causal premises of the model using state-of-the-art techniques, including pharmacological and electrophysiological interventions. Based on these insights I will for the first time apply personalized brain stimulation to anxiety patients. Clinically, this project should open the way to effective intervention with fearful avoidance in anxiety disorders that rank among the most common, costly and persistent mental disorders. Theoretically, conceptualizing transient psychophysiological states as causal factor in AA-decision models is essential to understanding passive and active avoidance. Optimizing AA-decisions also holds broad societal relevance given currently increased fearful avoidance of outgroups.

2 000 000 €

Start date: 2019-01-01, End date: 2024-06-30