ERC FUNDED PROJECTS

The realization of high-performance micro-supercapacitors is currently a big challenge but the ineluctable applications requiring such miniaturized energy storage devices are continuously emerging, from wearable electronic gadgets to wireless sensor networks. Although they store less energy than micro-batteries, micro-supercapacitors can be charged and discharged very rapidly and exhibit a quasi-unlimited lifetime. The global scientific research is consequently largely focused on the improvement of their capacitance and energetic performances. However, to date, they are still far from being able to power sensors or electronic components. Here I propose a 3D paradigm shift of micro-supercapacitor design to ensure increased energy storage capacities. Hydrous ruthenium dioxide (RuO2) is a pseudocapacitive material for supercapacitor electrode well-known for its high capacitance. A thin-film of ruthenium will be deposited by atomic layer deposition (ALD), followed by an electrochemical oxidation process, onto a high-surface-area 3D current collector prepared via an ingenious dynamic template built with hydrogen bubbles. The structural features of these 3D architectures will be controllably tailored by the processing methodologies. These electrodes will be combined with an innovative electrolyte in solid form (a protic ionogel) able to operate over an extended cell voltage. In a parallel investigation, we will develop a fundamental understanding of electrochemical reactions occurring at the nanoscale with a FIB-patterned (Focused Ion Beam) RuO2 nano-supercapacitor. The resulting 3D micro-supercapacitors should display extremely high power, long lifetime and – for the first time – energy densities competing or even exceeding that of micro-batteries. As a key achievement, prototypes will be designed using a new concept based on a self-adaptative micro-supercapacitors matrix, which arranges itself according to the global amount of energy stored.

1 673 438 €

Start date: 2018-04-01, End date: 2023-03-31

This project investigates the two-way relationship between spatio-temporal genome organization and coordinated gene regulation, through an approach at the interface between physics, computer science and biology. In the nucleus, preferred positions are observed from chromosomes to single genes, in relation to normal and pathological cellular states. Evidence indicates a complex spatio-temporal coupling between co-regulated genes: e.g. certain genes cluster spatially when responding to similar factors and transcriptional noise patterns suggest domain-wide mechanisms. Yet, no individual experiment allows probing transcriptional coordination in 4 dimensions (FISH, live locus tracking, Hi-C...). Interpreting such data also critically requires theory (stochastic processes, statistical physics…). A lack of appropriate experimental/analytical approaches is impairing our understanding of the 4D genome. Our proposal combines cutting-edge single-molecule imaging, signal-theory data analysis and physical modeling to study how genes coordinate in space and time in a single nucleus. Our objectives are to understand (a) competition/recycling of shared resources between genes within subnuclear compartments, (b) how enhancers communicate with genes domain-wide, and (c) the role of local conformational dynamics and supercoiling in gene co-regulation. Our organizing hypothesis is that, by acting on their microenvironment, genes shape their co-expression with other genes. Building upon my expertise, we will use dual-color MS2/PP7 RNA labeling to visualize for the first time transcription and motion of pairs of hormone-responsive genes in real time. With our innovative signal analysis tools, we will extract spatio-temporal signatures of underlying processes, which we will investigate with stochastic modeling and validate through experimental perturbations. We expect to uncover how the functional organization of the linear genome relates to its physical properties and dynamics in 4D.

1 499 750 €

Start date: 2018-04-01, End date: 2023-03-31

The emergence of life is one of the most fascinating and yet largely unsolved questions in the natural sciences, and thus a significant challenge for scientists from many disciplines. There is growing evidence that ribonucleic acid (RNA) polymers, which are capable of genetic information storage and self-catalysis, were involved in the early forms of life. But despite recent progress, RNA synthesis without biological machineries is very challenging. The current project aims at understanding how to synthesize RNA in abiotic conditions. I will solve problems associated with three critical aspects of RNA formation that I will rationalize at a molecular level: (i) accumulation of precursors, (ii) formation of a chemical bond between RNA monomers, and (iii) tolerance for alternative backbone sugars or linkages. Because I will study problems ranging from the formation of chemical bonds up to the stability of large biopolymers, I propose an original computational multi-scale approach combining techniques that range from quantum calculations to large-scale all-atom simulations, employed together with efficient enhanced-sampling algorithms, forcefield improvement, cutting-edge analysis methods and model development. My objectives are the following: 1 • To explain why the poorly-understood thermally-driven process of thermophoresis can contribute to the accumulation of dilute precursors. 2 • To understand why linking RNA monomers with phosphoester bonds is so difficult, to understand the molecular mechanism of possible catalysts and to suggest key improvements. 3 • To rationalize the molecular basis for RNA tolerance for alternative backbone sugars or linkages that have probably been incorporated in abiotic conditions. This unique in-silico laboratory setup should significantly impact our comprehension of life’s origin by overcoming major obstacles to RNA abiotic formation, and in addition will reveal significant orthogonal outcomes for (bio)technological applications.

1 497 031 €

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

The understanding of spatial, social and dynamical organization of large numbers of agents is presently a fundamental issue in modern science. ADORA focuses on problems motivated by biology because, more than anywhere else, access to precise and many data has opened the route to novel and complex biomathematical models. The problems we address are written in terms of nonlinear partial differential equations. The flux-limited Keller-Segel system, the integrate-and-fire Fokker-Planck equation, kinetic equations with internal state, nonlocal parabolic equations and constrained Hamilton-Jacobi equations are among examples of the equations under investigation. The role of mathematics is not only to understand the analytical structure of these new problems, but it is also to explain the qualitative behavior of solutions and to quantify their properties. The challenge arises here because these goals should be achieved through a hierarchy of scales. Indeed, the problems under consideration share the common feature that the large scale behavior cannot be understood precisely without access to a hierarchy of finer scales, down to the individual behavior and sometimes its molecular determinants. Major difficulties arise because the numerous scales present in these equations have to be discovered and singularities appear in the asymptotic process which yields deep compactness obstructions. Our vision is that the complexity inherent to models of biology can be enlightened by mathematical analysis and a classification of the possible asymptotic regimes. However an enormous effort is needed to uncover the equations intimate mathematical structures, and bring them at the level of conceptual understanding they deserve being given the applications motivating these questions which range from medical science or neuroscience to cell biology.

2 192 500 €

Start date: 2017-09-01, End date: 2022-08-31

The goal of this project is to investigate two conjectures in arithmetic geometry pertaining to the geometry of projective varieties over finite and number fields. These two conjectures, formulated by Tate and Grothendieck in the 1960s, predict which cohomology classes are chern classes of line bundles. They both form an arithmetic counterpart of a theorem of Lefschetz, proved in the 1940s, which itself is the only known case of the Hodge conjecture. These two long-standing conjectures are one of the aspects of a more general web of questions regarding the topology of algebraic varieties which have been emphasized by Grothendieck and have since had a central role in modern arithmetic geometry. Special cases of these conjectures, appearing for instance in the work of Tate, Deligne, Faltings, Schneider-Lang, Masser-Wüstholz, have all had important consequences. My goal is to investigate different lines of attack towards these conjectures, building on recent work on myself and Jean-Benoît Bost on related problems. The two main directions of the proposal are as follows. Over finite fields, the Tate conjecture is related to finiteness results for certain cohomological objects. I want to understand how to relate these to hidden boundedness properties of algebraic varieties that have appeared in my recent geometric proof of the Tate conjecture for K3 surfaces. The existence and relevance of a theory of Donaldson invariants for moduli spaces of twisted sheaves over finite fields seems to be a promising and novel direction. Over number fields, I want to combine the geometric insight above with algebraization techniques developed by Bost. In a joint project, we want to investigate how these can be used to first understand geometrically major results in transcendence theory and then attack the Grothendieck period conjecture for divisors via a number-theoretic and complex-analytic understanding of universal vector extensions of abelian schemes over curves.

1 222 329 €

Start date: 2016-12-01, End date: 2021-11-30

DNA repair pathways evolved as an intricate network that senses DNA damage and resolves it in order to minimise genetic lesions and thus preventing tumour formation. Gaining in recognition the last few years, the alternative end-joining (alt-EJ) DNA repair pathway was recently shown to be up-regulated and required for cancer cell viability in the absence of homologous recombination-mediated repair (HR). Despite this integral role, the alt-EJ repair pathway remains poorly characterised in humans. As such, its molecular composition, regulation and crosstalk with HR and other repair pathways remain elusive. Additionally, the contribution of the alt-EJ pathway to tumour progression as well as the identification of a mutational signature associated with the use of alt-EJ has not yet been investigated. Moreover, the clinical relevance of developing small-molecule inhibitors targeting players in the alt-EJ pathway, such as the polymerase Pol Theta (Polθ), is of importance as current anticancer drug treatments have shown limited effectiveness in achieving cancer remission in patients with HR-deficient (HRD) tumours. Here, we propose a novel, multidisciplinary approach that aims to characterise the players and mechanisms of action involved in the utilisation of alt-EJ in cancer. This understanding will better elucidate the changing interplay between different DNA repair pathways, thus shedding light on whether and how the use of alt-EJ contributes to the pathogenic history and survival of HRD tumours, eventually paving the way for the development of novel anticancer therapeutics. For all the abovementioned reasons, we are convinced this project will have important implications in: 1) elucidating critical interconnections between DNA repair pathways, 2) improving the basic understanding of the composition, regulation and function of the alt-EJ pathway, and 3) facilitating the development of new synthetic lethality-based chemotherapeutics for the treatment of HRD tumours.

1 498 750 €

Start date: 2017-07-01, End date: 2022-06-30

We are concerned with localization properties of solutions to hyperbolic PDEs, especially problems with a geometric component: how do boundaries and heterogeneous media influence spreading and concentration of solutions. While our first focus is on wave and Schrödinger equations on manifolds with boundary, strong connections exist with phase space localization for (clusters of) eigenfunctions, which are of independent interest. Motivations come from nonlinear dispersive models (in physically relevant settings), properties of eigenfunctions in quantum chaos (related to both physics of optic fiber design as well as number theoretic questions), or harmonic analysis on manifolds. Waves propagation in real life physics occur in media which are neither homogeneous or spatially infinity. The birth of radar/sonar technologies (and the raise of computed tomography) greatly motivated numerous developments in microlocal analysis and the linear theory. Only recently toy nonlinear models have been studied on a curved background, sometimes compact or rough. Understanding how to extend such tools, dealing with wave dispersion or focusing, will allow us to significantly progress in our mathematical understanding of physically relevant models. There, boundaries appear naturally and most earlier developments related to propagation of singularities in this context have limited scope with respect to crucial dispersive effects. Despite great progress over the last decade, driven by the study of quasilinear equations, our knowledge is still very limited. Going beyond this recent activity requires new tools whose development is at the heart of this proposal, including good approximate solutions (parametrices) going over arbitrarily large numbers of caustics, sharp pointwise bounds on Green functions, development of efficient wave packets methods, quantitative refinements of propagation of singularities (with direct applications in control theory), only to name a few important ones.

1 293 763 €

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

Single-photon sources (SPSs) are systems capable of emitting photons one by one. These sources are of major importance for quantum-information science and applications. SPSs experiments generally rely on the optical excitation of two level systems of atomic-scale dimensions (single-molecules, vacancies in diamond…). Many fundamental questions related to the nature of these sources and the impact of their environment remain to be explored: Can SPSs be addressed with atomic-scale spatial accuracy? How do the nanometer-scale distance or the orientation between two (or more) SPSs affect their emission properties? Does coherence emerge from the proximity between the sources? Do these structures still behave as SPSs or do they lead to the emission of correlated photons? How can we then control the degree of entanglement between the sources? Can we remotely excite the emission of these sources by using molecular chains as charge-carrying wires? Can we couple SPSs embodied in one or two-dimensional arrays? How does mechanical stress or localised plasmons affect the properties of an electrically-driven SPS? Answering these questions requires probing, manipulating and exciting SPSs with an atomic-scale precision. This is beyond what is attainable with an all-optical method. Since they can be confined to atomic-scale pathways we propose to use electrons rather than photons to excite the SPSs. This unconventional approach provides a direct access to the atomic-scale physics of SPSs and is relevant for the implementation of these sources in hybrid devices combining electronic and photonic components. To this end, a scanning probe microscope will be developed that provides simultaneous spatial, chemical, spectral, and temporal resolutions. Single-molecules and defects in monolayer transition metal dichalcogenides are SPSs that will be studied in the project, and which are respectively of interest for fundamental and more applied issues.

1 996 848 €

Start date: 2018-06-01, End date: 2023-05-31

The project ARTHUS aims at determining the physical origin of Dark Energy: in addition to the energy sources of the standard model of cosmology, effective terms arise through spatially averaging inhomogeneous cosmological models in General Relativity. It has been demonstrated that these additional terms can play the role of Dark Energy on large scales (but they can also mimic Dark Matter on scales of mass accumulations). The underlying rationale is that fluctuations in the Universe generically couple to spatially averaged intrinsic properties of space, such as its averaged scalar curvature, thus changing the global evolution of the effective (spatially averaged) cosmological model. At present, we understand these so- called backreaction effects only qualitatively. The project ARTHUS is directed towards a conclusive quantitative evaluation of these effects by developing generic and non-perturbative relativistic models of structure formation, by statistically measuring the key-variables of the models in observations and in simulation data, and by reinterpreting observational results in light of the new models. It is to be emphasized that there is no doubt about the existence of backreaction effects; the question is whether they are even capable of getting rid of the dark sources (as some models discussed in the literature suggest), or whether their impact is substantially smaller. The project thus addresses an essential issue of current cosmological research: to find pertinent answers concerning the quantitative impact of inhomogeneity effects, a necessary, worldwide recognized step toward high-precision cosmology. If the project objectives are attained, the results will have a far-reaching impact on theoretical and observational cosmology, on the interpretation of astronomical experiments such as Planck and Euclid, as well as on a wide spectrum of particle physics theories and experiments.

2 091 000 €

Start date: 2017-09-01, End date: 2022-08-31

The ERC starting grant GECOMETHODS, on which this POC is based, tackled problems of diffusion equations via geometric control methods. One of the most striking achievements of the project has been the development of an algorithm of image reconstruction based mainly on non-isotropic diffusion. This algorithm is bio-mimetic in the sense that it replicates the way in which the primary visual cortex V1 of mammals processes the signals arriving from the eyes. It has performances that are at the state of the art in image processing. These results together with others obtained in the ERC project show that image processing algorithms based on the functional architecture of V1 can go very far. However, the exceptional performances of the primary visual cortex V1 rely not only on the particular algorithm used, but also on the fact that such algorithm “runs” on a dedicated hardware having the following features: 1. an exceptional level of parallelism; 2. connections that are well adapted to transmit information in a non-isotropic way as it is required by the algorithms of image reconstruction and recognition. The idea of this POC is to create a dedicated hardware (called ARTIV1) emulating the functional architecture of V1 and hence having on one hand a huge degree of parallelism and on the other hand connections among the CPUs that reflect the non-isotropic structure of the visual cortex V1. Such a hardware that we plan to build as an integrated circuit with an industrial partner will be a veritable artificial visual cortex. It will be fully programmable and it will be able to perform many biomimetic image processing tasks that we expect to be exceptionally performant. ARTIV1 will come to the marked accompanied by some dedicated software for image reconstruction and image recognition. However we expect that other applications will be developed by customers, as for instance softwares for optical flow estimation or for sound processing.

149 937 €

Start date: 2017-04-01, End date: 2018-09-30

Which molecules are present in the atmosphere of exoplanets? What are their mass, radius and age? Do they have clouds, convection (atmospheric turbulence), fingering convection, or a circulation induced by irradiation? These questions are fundamental in exoplanetology in order to study issues such as planet formation and exoplanet habitability. Yet, the impact of fingering convection and circulation induced by irradiation remain poorly understood: - Fingering convection (triggered by gradients of mean-molecular-weight) has already been suggested to happen in stars (accumulation of heavy elements) and in brown dwarfs and exoplanets (chemical transition e.g. CO/CH4). A large-scale efficient turbulent transport of energy through the fingering instability can reduce the temperature gradient in the atmosphere and explain many observed spectral properties of brown dwarfs and exoplanets. Nonetheless, this large-scale efficiency is not yet characterized and standard approximations (Boussinesq) cannot be used to achieve this goal. - The interaction between atmospheric circulation and the fingering instability is an open question in the case of irradiated exoplanets. Fingering convection can change the location and magnitude of the hot spot induced by irradiation, whereas the hot deep atmosphere induced by irradiation can change the location of the chemical transitions that trigger the fingering instability. This project will characterize the impact of fingering convection in the atmosphere of stars, brown dwarfs, and exoplanets and its interaction with the circulation in the case of irradiated planets. By developing innovative numerical models, we will characterize the reduction of the temperature gradient of the atmosphere induced by the instability and study the impact of the circulation. We will then predict and interpret the mass, radius, and chemical composition of exoplanets that will be observed with future missions such as the James Webb Space Telescope (JWST).

1 500 000 €

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

The role of experience in language acquisition has been the focus of heated theoretical debates, between proponents of nativist views according to whom experience plays a minimal role and advocates of empiricist positions holding that experience, be it linguistic, social or other, is sufficient to account for language acquisition. Despite more than a half century of dedicated research efforts, the problem is not solved. The present project brings a novel perspective to this debate, combining hitherto unconnected research in language acquisition with recent advances in the neurophysiology of hearing and speech processing. Specifically, it claims that prenatal experience with speech, which mainly consists of prosody due to the filtering effects of the womb, is what shapes the speech perception system, laying the foundations of subsequent language learning. Prosody is thus the cue that links genetically endowed predispositions present in the initial state with language experience. The proposal links the behavioral and neural levels, arguing that the hierarchy of the neural oscillations corresponds to a unique developmental chronology in human infants’ experience with speech and language. The project uses state-of-the-art brain imaging techniques, EEG & NIRS, with monolingual full term newborns, as well as full-term bilingual, preterm and deaf newborns to investigate the link between prenatal experience and subsequent language acquisition. It proposes to follow the developmental trajectories of these four populations from birth to 6 and 9 months of age.

1 621 250 €

Start date: 2018-06-01, End date: 2023-05-31

Although the T cell antigen receptor (TCR) occupies a central place in T cell physiology, it does not work in isolation and the signals it triggers are tuned by receptors that convey positive (costimulators) and negative (coinhibitors) informations. We lack a satisfying comprehension of the way T cells integrate such multiple inputs to make informed decisions. The proteomics-based methodology we developed around the TCR places us in a favorable situation to decode at systems-level the crosstalk between the TCR, the CD28 costimulator and the PD-1 coinhibitor signaling pathways. The novelty of our approach stems from (1) its use of primary T cells, (2) its capacity to probe the architecture and dynamics of signalosomes resulting from T cell-antigen presenting cell encounters, (3) the attention we pay to the stoichiometry of the studied signalosomes, a key parameter largely ignored in previous studies, and (4) its multidisciplinary nature straddling molecular and organismal scales. Our specific aims are: Aim 1. To understand how the TCR and CD28 signaling pathways cooperate to achieve optimal T cell responses. Aim 2. To determine whether CD28 is the sole target of the PD-1 coinhibitor. Aim 3. To determine how under inflammatory conditions CD28 functions can be superseded by those of OX40, a costimulator of the TNFR superfamily. Aim 4. To unveil how malfunctions of LAT, a key signaling hub used by the TCR, disrupt the TCR-CD28 crosstalk and result in unique pathogenic T cells that by becoming ‘autistic’ to TCR signals and addicted to CD28 signals lead to severe immunopathologies. We think that combining genetic, epigenomics, proteomics, and computational approaches creates ideal experimental conditions to understand at system-levels how TCR, costimulatory, coinhibitory and inflammatory signals are integrated during T cell clonal expansion. Although of fundamental nature, our project should help understanding the harmful role PD-1 plays during anti-tumoral responses.

2 000 000 €

Start date: 2018-08-01, End date: 2022-07-31

This proposal addresses a pressing need from emerging big data applications such as genomics and data center monitoring: besides the scale of processing, big data systems must also enable perpetual, low-latency processing for a broad set of analytical tasks, referred to as big and fast data analysis. Today’s technology falls severely short for such needs due to the lack of support of complex analytics with scale, low latency, and strong guarantees of user performance requirements. To bridge the gap, this proposal tackles a grand challenge: “How do we design an algorithmic foundation that enables the development of all necessary pillars of big and fast data analysis?” This proposal considers three pillars: 1) Parallelism: There is a fundamental tension between data parallelism (for scale) and pipeline parallelism (for low latency). We propose new approaches based on intelligent use of memory and workload properties to integrate both forms of parallelism. 2) Analytics: The literature lacks a large body of algorithms for critical order-related analytics to be run under data and pipeline parallelism. We propose new algorithmic frameworks to enable such analytics. 3) Optimization: To run analytics, today's big data systems are best effort only. We transform such systems into a principled optimization framework that suits the new characteristics of big data infrastructure and adapts to meet user performance requirements. The scale and complexity of the proposed algorithm design makes this project high-risk, at the same time, high-gain: it will lay a solid foundation for big and fast data analysis, enabling a new integrated parallel processing paradigm, algorithms for critical order-related analytics, and a principled optimizer with strong performance guarantees. It will also broadly enable accelerated information discovery in emerging domains such as genomics, as well as economic benefits of early, well-informed decisions and reduced user payments.

2 472 752 €

Start date: 2017-09-01, End date: 2022-08-31

Bacterial biofilm formation is a paramount developmental process in both Gram-positive and Gram-negative species and in many pathogens has been associated with processes of horizontal gene transfer, antibiotic resistance development and pathogen persistence. Bacterial biofilms are collaborative sessile macrocolonies embedded in complex extracellular matrix that secures both mechanical resistance and a medium for intercellular exchange. Biogenesis platforms for the secretion of biofilm matrix components - many of which controlled directly or indirectly by the intracellular second messenger c-di-GMP - are important determinants for biofilm formation and bacterial disease, and therefore present compelling targets for the development of novel therapeutics. During my Ph.D. and post-doctoral work I studied the structure and function of c-di-GMP-sensing protein factors controling extracellular matrix production by DNA-binding at the transcription initiation level or by inside-out signalling mechanisms at the cell envelope, as well as membrane exporters involved directly in downstream matrix component secretion. Here, I propose to apply my expertise in microbiology, protein science and structural biology to study the structure and function of exopolysaccharide secretion systems in Gram-negative species. Using Pseudomonas aeruginosa, Vibrio spp. and Escherichia coli as model organisms, my team will aim to reveal the global architecture and individual building components of several expolysaccharide-producing protein megacomplexes. We will combine X-ray crystallography, biophysical and biochemical assays, electron microscopy and in cellulo functional studies to provide a comprehensive view of extracellular matrix production that spans the different resolution levels and presents molecular blueprints for the development of novel anti-infectives. Over the last year I have laid the foundation of these studies and have demonstrated the overall feasibility of the project.

1 499 901 €

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

Over the past decades, silicon became the most used material for electronic, however its indirect band gap limits its use for optics and optoelectronics. As a result alternatives semiconductor such as III-V and II-VI materials are used to address a broad range of complementary application such as LED, laser diode and photodiode. However in the infrared (IR), the material challenge becomes far more complex. New IR applications, such as flame detection or night car driving assistance are emerging and request low cost detectors. Current technologies, based on epitaxially grown semiconductors are unlikely to bring a cost disruption and organic electronics, often viewed as the alternative to silicon based materials is ineffective in the mid-IR. The blackQD project aims at transforming colloidal quantum dots (CQD) into the next generation of active material for IR detection. CQD are attracting a high interest because of their size tunable optical features and next challenges is their integration in optoelectronic devices and in particular for IR features. The project requires a combination of material knowledge, with clean room nanofabrication and IR photoconduction which is unique in Europe. I organize blackQD in three mains parts. The first part relates to the growth of mercury chalcogenides nanocrystals with unique tunable properties in the mid and far-IR. To design devices with enhanced properties, more needs to be known on the electronic structure of these nanomaterials. In part II, I propose to develop original methods to probe static and dynamic aspects of the electronic structure. Finally the main task of the project relates to the design of a new generation of transistors and IR detectors. I propose several geometries of demonstrator which for the first time integrate from the beginning the colloidal nature of the CQD and constrain of IR photodetection. The project more generally aims to develop a tool box for the design of the next generation of low cost IR.

1 499 903 €

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

Brain-Computer Interfaces (BCIs) are communication systems that enable users to send commands to computers through brain signals only, by measuring and processing these signals. Making computer control possible without any physical activity, BCIs have promised to revolutionize many application areas, notably assistive technologies, e.g., for wheelchair control, and human-machine interaction. Despite this promising potential, BCIs are still barely used outside laboratories, due to their current poor reliability. For instance, BCIs only using two imagined hand movements as mental commands decode, on average, less than 80% of these commands correctly, while 10 to 30% of users cannot control a BCI at all. A BCI should be considered a co-adaptive communication system: its users learn to encode commands in their brain signals (with mental imagery) that the machine learns to decode using signal processing. Most research efforts so far have been dedicated to decoding the commands. However, BCI control is a skill that users have to learn too. Unfortunately how BCI users learn to encode the commands is essential but is barely studied, i.e., fundamental knowledge about how users learn BCI control is lacking. Moreover standard training approaches are only based on heuristics, without satisfying human learning principles. Thus, poor BCI reliability is probably largely due to highly suboptimal user training. In order to obtain a truly reliable BCI we need to completely redefine user training approaches. To do so, I propose to study and statistically model how users learn to encode BCI commands. Then, based on human learning principles and this model, I propose to create a new generation of BCIs which ensure that users learn how to successfully encode commands with high signal-to-noise ratio in their brain signals, hence making BCIs dramatically more reliable. Such a reliable BCI could positively change human-machine interaction as BCIs have promised but failed to do so far.

1 498 751 €

Start date: 2017-07-01, End date: 2022-06-30

Intercellular communication is critical for multicellularity. It coordinates the activities within individual cells to support the function of an organism as a whole. Plants have developed remarkable cellular machines -the Plasmodesmata (PD) pores- which interconnect every single cell within the plant body, establishing direct membrane and cytoplasmic continuity, a situation unique to plants. PD are indispensable for plant life. They control the flux of molecules between cells and are decisive for development, environmental adaptation and defence signalling. However, how PD integrate signalling to coordinate responses at a multicellular level remains unclear. A striking feature of PD organisation, setting them apart from animal cell junctions, is a strand of endoplasmic reticulum (ER) running through the pore, tethered extremely tight (~10nm) to the plasma membrane (PM) by unidentified “spokes”. To date, the function of ER-PM contacts at PD remains a complete enigma. We don’t know how and why the two organelles come together at PD cellular junctions. I recently proposed that ER-PM tethering is in fact central to PD function. In this project I will investigate the question of how integrated cellular responses benefit from organelle cross-talk at PD. The project integrates proteomic/bioinformatic approaches, biophysical/modelling methods and ultra-high resolution 3D imaging into molecular cell biology of plant cell-to-cell communication and will, for the first time, directly address the mechanism and function of ER-PM contacts at PD. We will pursue three complementary objectives to attain our goal: 1) Identify the mechanisms of PD membrane-tethering at the molecular level 2) Elucidate the dynamics and 3D architecture of ER-PM contact sites at PD 3) Uncover the function of ER-PM apposition for plant intercellular communication. Overall, the project will pioneer a radically new perspective on PD-mediated cell-to-cell communication, a fundamental aspect of plant biology

1 999 840 €

Start date: 2018-06-01, End date: 2023-05-31

This project aims at developing and disseminating a new class of ultrasensitive and vectorial force field sensors to build the next generation of scanning probes with improved sensitivity and vectorial readout capacity. The vibrations of a singly clamped silicon carbide nanowire (NW) are readout by optical techniques. Its vibrating extremity oscillates in both transverse directions with quasi-degenerated frequencies due to its quasi-cylindrical geometry. When approaching the NW above a sample surface it experiences an additional force field due to the sample-NW interaction which modifies its mechanical properties. The force field can be fully derived by monitoring frequency shifts and eigenmode rotations. The measurement principle was demonstrated during the HQNOM ERC project by monitoring the perturbation of the NW Brownian motion, its random thermal noise in 2D induced by a voltage biased electrostatic tip. An impressive sensitivity to force field gradients varying by less than 1e-18N over the nanometer sized Brownian motion was demonstrated, as well as a fully vectorial readout capacity which is unaccessible to existing 1D force probes. This vectorial sensitivity, combined with the one-millon-fold improvement in force sensitivity over commercial atomic force microscopes is the starting point of the POC project. The objective is to ensure a wide dissemination of this extraordinary vectorial force field sensors and to progress towards an industrial outreach of the apparatus. To do so, a demonstration prototype will be developed and will serve as a workhorse for the second step, the dissemination phase of the apparatus towards a broader scientific and industrial community.

150 000 €

Start date: 2017-11-01, End date: 2019-04-30

Faithful chromosome segregation in all eukaryotes relies on centromeres, the chromosomal sites that recruit kinetochore proteins and mediate spindle attachment during cell division. Fundamental to centromere function is a histone H3 variant, CenH3, that initiates kinetochore assembly on centromeric DNA. CenH3 is conserved throughout most eukaryotes; its deletion is lethal in all organisms tested. These findings established the paradigm that CenH3 is an absolute requirement for centromere function. My recent findings undermined this paradigm of CenH3 essentiality. I showed that CenH3 was lost independently in four lineages of insects. These losses are concomitant with dramatic changes in their centromeric architecture, in which each lineage independently transitioned from monocentromeres (where microtubules attach to a single chromosomal region) to holocentromeres (where microtubules attach along the entire length of the chromosome). Here, I aim to characterize this unique CenH3-deficient chromosome segregation pathway. Using proteomic and genomic approaches in lepidopteran cell lines, I will determine the mechanism of CenH3-independent kinetochore assembly that led to the establishment of their holocentric architecture. Using comparative genomic approaches, I will determine whether this kinetochore assembly pathway has recurrently evolved over the course of 400 million years of evolution and its impact on the chromosome segregation machinery. My discovery of CenH3 loss in holocentric insects establishes a new class of centromeres. My research will reveal how CenH3 that is essential in most other eukaryotes, could have become dispensable in holocentric insects. Since the evolution of this CenH3-independent chromosome segregation pathway is associated with the independent rises of holocentric architectures, my research will also provide the first insights into the transition from a monocentromere to a holocentromere.

1 497 500 €

Start date: 2018-04-01, End date: 2023-03-31

The failure of metallic materials caused by corrosion strongly impacts our society with cost, safety, health and performance issues. The mechanisms of corrosion propagation are fairly well understood, and various means of mitigation are known even if research is still necessary to improve this knowledge or to develop corrosion protection for the application of new materials. The vision of CIMNAS is that a major breakthrough for corrosion protection lies in a deep understanding and control of the initiation stage triggering corrosion. Corrosion initiation takes place at the atomic/molecular scale or at a scale of a few nanometres (the nanoscale) on metal and alloy surfaces, metallic, oxidised or coated, and interacting with the corroding environment. The mission of CIMNAS is to challenge the difficulty of understanding corrosion initiation at the nanometric/atomic scale on such complex interfaces, ultimately aiming at designing more robust metallic surfaces via the understanding of corrosion mechanisms. The project is constructed on new ideas to achieve three knowledge breakthroughs, each answering a key question for the understanding of corrosion initiation on metal and alloy surfaces. It is envisioned that the model approach used and the achieved breakthroughs will open up a new horizon for research on corrosion initiation mechanisms at the nanoscale, and new opportunities for a knowledge-based design of novel corrosion protection technologies. Technologies presently at low TRL (Technology Readiness Level) will benefit from these breakthroughs. Resources will include a team of highly experienced and recognised researchers headed by the PI, a unique apparatus recently installed at the PI’s lab, integrating surface spectroscopy, microscopy, and electrochemistry for in situ measurements in a closed system, novel experimental approaches, and a strong complementarity of experiments and modelling.

1 657 056 €

Start date: 2017-09-01, End date: 2021-08-31

I am willing to solve several well-known models from combinatorics, probability theory and statistical mechanics: the Ising model on isoradial graphs, dimer models, spanning forests, random walks in cones, occupation time problems. Although completely unrelated a priori, these models have the common feature of being presumed “exactly solvable” models, for which surprising and spectacular formulas should exist for quantities of interest. This is captured by the title “Elliptic Combinatorics”, the wording elliptic referring to the use of special functions, in a broad sense: algebraic/differentially finite (or holonomic)/diagonals/(hyper)elliptic/ hypergeometric/etc. Besides the exciting nature of the models which we aim at solving, one main strength of our project lies in the variety of modern methods and fields that we cover: combinatorics, probability, algebra (representation theory), computer algebra, algebraic geometry, with a spectrum going from applied to pure mathematics. We propose in addition two major applications, in finance (Markovian order books) and in population biology (evolution of multitype populations). We plan to work in close collaborations with researchers from these fields, to eventually apply our results (study of extinction probabilities for self-incompatible flower populations, for instance).

1 242 400 €

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

I propose for funding to construct a spectrometer to map in 3-D the intensity due to line emission, a technique known as Intensity Mapping. Instead of detecting individual galaxies, this emerging technique measures signal fluctuations produced by the combined emission of the galaxy population on large regions of the sky in a wide frequency (i.e. redshift) band, and thus increases sensitivity to faint sources. Capitalizing on a recent technology breakthrough, our intensity mapping experiment will measure the 3-D fluctuations of the [CII] line at redshifts 4.5<z<8.5. [CII] is one of the most valuable star formation tracers at high redshift. My project will answer the outstanding questions of whether dusty star-formation contributes to early galaxy evolution, and whether dusty galaxies play an important role in shaping cosmic reionization. My team will first build, test, and finally install the instrument on the APEX antenna following an agreement with APEX partners. The spectrometer will be based on the state-of-the-art development of new arrays in the millimeter using Kinetic Inductance Detectors. Spectra (200-360 GHz) will be obtained by a fast Martin-Puplett interferometer. Then, we will observe with CONCERTO a few square degrees and offer a straight forward alternative for probing star formation and dust build-up in the early Universe. Finally, CONCERTO will set to music the various cosmic evolution probes. Cross-correlation of the signals will be used in particular to capture the topology of the end of reionization era. CONCERTO will be one of two instruments in the world to perform intensity mapping of the [CII] line in the short term. The novel methodology is extremely promising as it targets an unexplored observable touching on some of the fundamental processes building the early universe. In the flourishing of new ideas in the intensity-mapping field, CONCERTO lies at the forefront.

3 499 942 €

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

According to the Centre for Research on the Epidemiology of Disasters (CRED), earthquakes are responsible for more than half of the total human losses due to natural disasters from 1994 to 2003. There is no doubt that earthquakes are lethal and costly. CoQuake proposes an alternative, ground-breaking approach for avoiding catastrophic earthquakes by inducing them at a lower energetic level. Earthquakes are a natural phenomenon that we cannot avoid, but –for the first time– in CoQuake I will show that it is possible to control them, hence reducing the seismic risk, fatalities and economic cost. CoQuake goes beyond the state-of-the-art by proposing an innovative methodology for investigating the effect and the controllability of various stimulating techniques that can reactivate seismic faults. It involves large-scale, accurate simulations of fault systems based on constitutive laws derived from micromechanical, grain-by-grain simulations under Thermo-Hydro-Chemo-Mechanical couplings (THMC), which are not calibrated on the basis of ad-hoc empirical and inaccurate constitutive laws. A pioneer experimental research programme and the design and construction of a new apparatus of metric scale, will demonstrate CoQuake’s proof-of-principle and it will help to explore the transition from aseismic to seismic slip. CoQuake is an interdisciplinary project as it takes knowledge from various fields of engineering, computational mechanics, geomechanics, mathematics and geophysics. CoQuake opens a new field and new line of research in earthquake mechanics and engineering, with a direct impact on humanity and science.

1 499 999 €

Start date: 2018-06-01, End date: 2023-05-31

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

Low temperature matter exhibits a spectacular variety of highly ordered states that occur through phase transitions. In quantum systems, phase transitions and associated critical phenomena constitute a central issue of modern physics. Wilson’s theory of renormalization showed that very different physical systems could be unified under the same universality class characterized by critical exponents. The high degree of control offered by ultracold atom experiments sets them as an ideal platform for the investigation of phase transitions and critical phenomena. CRITISUP2 aims at exploring criticality in superfluid spin ½ Fermi gases where the interplay between temperature spin polarization and interactions is at the origin of a rich phase diagram and a variety of phase transitions. We will measure the corresponding static and dynamic critical exponents, and search for the long-sought Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) phase predicted over 50 years ago. We will also study the phase diagram and critical counterflow of dual Bose-Fermi superfluids which have emerged as a new paradigm of quantum matter. Cutting-edge Bold Diagrammatic Monte Carlo and new resummation methods, developed in-house, will be confronted to the experiments on the one hand, and provide answers to debated questions on the other. The expected outcomes of CRITISUP2 will constitute a major leap forward relevant for several fields of modern physics, ranging from condensed-matter to astrophysics, nuclear physics, and high energy physics.

2 246 536 €

Start date: 2017-05-01, End date: 2022-04-30

Emergence of a large number of distributed decision and control systems (e.g., in health care, transportation, and energy management), combined with increasing demands of traditional communications (e.g., due to multiview videos), create an imminent need for highly improved communication systems. We advocate that—combined with improvements in battery, antenna, and chip technologies—context- and/or task-oriented communication techniques will bring the desired breakthrough. Specifically, context- oriented techniques will greatly improve performance, because future networks have complex infrastructures (with cache-memories, cloud-RANs, etc.) allowing the terminals to collect side-informations about other terminals’ data or signals, and because many distributed decision systems rely on numerous devices with correlated measurements. Task-oriented techniques promise even larger gains, especially in distributed decision systems where decisions take value on a small range, and thus the traditional approach of communicating sequences of observed signals results in a huge overhead. Information theory, and in particular distributed joint source-channel coding, provides a general framework for designing context-oriented communication techniques. Such a general framework is missing for task-oriented communication. Previous results indicate that creative usages of information theory on its frontier to statistics and decision theory are well-suited for designing task-oriented communication techniques for applications as diverse as coordination of smart devices, distributed hypothesis testing, and clustering of data. Our goal is to design context- and/or task-oriented communication techniques for these three applications and for cache-aided communication. Besides the high gains that our new techniques bring directly to these applications, the complementarity of our applications and obtained results will facilitate a future general framework for context- and task-oriented communication.

1 495 288 €

Start date: 2017-05-01, End date: 2022-04-30

Designers draw extensively to externalize their ideas and communicate with others. However, drawings are currently not directly interpretable by computers. To test their ideas against physical reality, designers have to create 3D models suitable for simulation and 3D printing. However, the visceral and approximate nature of drawing clashes with the tediousness and rigidity of 3D modeling. As a result, designers only model finalized concepts, and have no feedback on feasibility during creative exploration. Our ambition is to bring the power of 3D engineering tools to the creative phase of design by automatically estimating 3D models from drawings. However, this problem is ill-posed: a point in the drawing can lie anywhere in depth. Existing solutions are limited to simple shapes, or require user input to “explain” to the computer how to interpret the drawing. Our originality is to exploit professional drawing techniques that designers developed to communicate shape most efficiently. Each technique provides geometric constraints that help viewers understand drawings, and that we shall leverage for 3D reconstruction. Our first challenge is to formalize common drawing techniques and derive how they constrain 3D shape. Our second challenge is to identify which techniques are used in a drawing. We cast this problem as the joint optimization of discrete variables indicating which constraints apply, and continuous variables representing the 3D model that best satisfies these constraints. But evaluating all constraint configurations is impractical. To solve this inverse problem, we will first develop forward algorithms that synthesize drawings from 3D models. Our idea is to use this synthetic data to train machine learning algorithms that predict the likelihood that constraints apply in a given drawing. In addition to tackling the long-standing problem of single-image 3D reconstruction, our research will significantly tighten design and engineering for rapid prototyping.

1 482 761 €

Start date: 2017-02-01, End date: 2022-01-31

Dark matter (DM) is a ubiquitous yet invisible presence in our universe. It dictated how galaxies formed in the first place, and now moves stars around them at puzzling speeds. The DM mass in the universe is known to be five times that of ordinary matter; yet its true nature remains elusive. Weakly interacting massive particles (WIMPs), relics from the early universe, are a compelling explanation chased by sensitive experiments in deep underground laboratories. However, searches for heavy WIMPs (≈100 times the proton mass), the most theoretically natural candidates, have been so far unsuccessful. Nor has evidence for such heavy particles yet been found at the CERN Large Hadron Collider. Alternative scenarios are now under scrutiny, such as the existence of a hidden sector of lighter DM particles that interact, differently than WIMPs, also with electrons. DAMIC-M (Dark Matter In CCDs at Modane) will search beyond the heavy WIMP paradigm by detecting nuclear recoils and electrons induced by light DM in charge-coupled devices (CCDs). The 0.5 kg detector will be installed at the Laboratoire Souterrain de Modane, France. In this novel and unconventional use of CCDs, which are commonly employed for digital imaging in astronomical telescopes, the ionization charge will be detected in the most massive CCDs ever built with exquisite spatial resolution (15 μm x 15 μm pixel). The crucial innovation in these devices is the non-destructive, repetitive measurement of the pixel charge, which results in the high-resolution detection of a single electron and unprecedented sensitivity to light DM (≈ eV energies are enough to free an electron in silicon). By counting individual charges in a detector with extremely low leakage current – a combination unmatched by any other DM experiment – DAMIC-M will take a leap forward of several orders of magnitude in the exploration of the hidden sector, a jump that may be rewarded by serendipitous discovery.

3 349 563 €

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

The switch from parchment to paper had a fundamental impact on later medieval universities, equivalent to the shift to Open Access today, hindering some intellectual practices while encouraging others. The DEBATE project identifies a neglected genre of latin texts that flourished on paper, the Principia, which record the public confrontations between candidates (socii) for the title of doctor. These debates, imposed by university statutes throughout Europe as annual exercises linked to lectures on the Sentences (the medieval parallel to our PhD thesis), forced the candidate to reveal his innovative theories (sheets of papers were exchanged among the socii beforehand), display his erudition and prove his intellectual prowess before a large audience. The futuristic discussion usually exceeded the confines of one discipline and allowed the bachelor to indulge his interdisciplinary interests, employing science, theology, mathematics, politics, literature, and rhetoric in his polemics against his colleagues. Principia thus reveal the cutting edge method of fostering science in later medieval universities. The DEBATE team intends to identify new manuscripts, edit the texts, establish authorship for anonymous fragments and propose an interpretation that will help explain how innovation was a primordial target in medieval academia. Putting together all the surviving texts of Principia produced in various cultural contexts, this project will provide a wealth of material that will bring about a basic change in our understanding of the mechanism of the production of academic knowledge in the early universities all around Europe.The project is designed to promote erudition by combining a palaeographical, codicological, editorial and hermeneutical approach, aiming to open an advanced area of inquiry focusing on an intellectual practice that bound together medieval universities from different geographical and cultural regions: Paris, Bologna, Vienna, Prague, Krakow and Cologne.

1 997 976 €

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

We are designing molecular networks - based on DNA programing- to detect extremely dilute molecular signals and robustly separate them from background noise. This could have relevant applications in the field of molecular diagnostics, in particular in the area of ultra-sensitive testing of nucleic acids from liquid biopsy for example for the detection of circulating microRNA. MicroRNA are difficult targets for standard ultra sensitive techniques such as quantitative PCR, but, because of their presence in the blood stream, they also represent an emerging class of important biomarkers for a wide range of diseases, including cancer. This project will allow us to put together a proof of principle, based of clinically relevant targets and sample, that will clearly demonstrate the benefit of our approach for the molecular diagnostic of microRNA, in terms of sensibility, multiplexing, robustness, modularity and simplicity in sample preparation.

149 852 €

Start date: 2017-12-01, End date: 2019-05-31

The desert is a paradox: it is at the same time arid and rich in resources, a margin and an interface. Far from being a no man’s land, it is a social space of linked solidarities. The “Desert Networks” project aims to explore the reticular organisation of such a zone by focusing on the southern part of the Eastern Desert of Egypt. Located between the Nile and the Red Sea, it has always been a tantalizing region for Egypt and beyond. Its ancient remains are admirably preserved and ancient sources about and from the region itself are numerous. Yet, the history of its occupation and appropriation remains a static and compartmentalized one. Therefore, the ambition of the project is to cross disciplinary borders and achieve an epistemological break by working for the first time in and on the Eastern desert as a dynamic object, both from a long-term perspective (mid-second millennium BC - late third century AD), and by analysing the patterns and functions of the different networks that linked its various nodes using the connectivity theory that reshaped scholarly paradigms for the Mediterranean in the 2000s. As the head of the French Eastern Desert mission, the PI will co-ordinate a multidisciplinary team. For the first time, the project will gather all the data unearthed in the region over 300 years, as well as the expected data from the excavations conducted by the project, in a database linked with a GIS. A collaborative and online open access map of the Eastern Desert will be created and will serve for the spatial analyses and rendering of the real, economic and social networks in the area. These networks evolved over time and through a shifting geography, as people experienced different perceptions of space. By assessing all these facets and confronting the archaeological material and written evidence, our final objective is to write a new history of the Eastern Desert from Pharaonic to Roman times, focusing on its networks and evaluating their meaning.

1 499 844 €

Start date: 2017-11-01, End date: 2022-10-31

Nobody knows why a soap bubble collapses. When the liquid film forming the bubble, stabilised by surfactants, becomes too thin, it collapses. This seemingly simple problem, ruled by the classical laws of fluid mechanics and of statistical physics, is still a challenge for the physicist. The rupture criteria based on a stability analysis in the vicinity of the film equilibrium state fail to reproduce the observations. However the film ruptures in a foam obey some simple phenomenological laws, which suggest that underlying fundamental laws exist and wait to be determined. The state-of-the-art conjecture is that ruptures are related to hydrodynamical processes in the films, a field in which I have now an international leadership. Recent experimental data I obtained open the possibility to address this question using a fully non-linear approach in the far from equilibrium regime. In this aim, DISFILM will develop an innovative technique to measure the interface velocity and surfactant concentration, based on the use of fluorescent surfactants. The risk relies in the adaptation to dynamical conditions of advanced optical techniques. These quantities have never been measured on flowing interfaces yet, and my technique will be an important breakthrough in the field of free interface flows in presence of surfactants. A set-up will be designed to reproduce on few thin films the deformations occurring in a foam sample. The dynamical path leading to the rupture of the film will be identified and modelled. The results obtained on an isolated film will be implemented to predict the 3D foam stability and the approach will be extended to emulsions. Foams and emulsions are widely used in industry and most of the stability issues have been solved. Nevertheless, most of the industrial formulations must currently be modified in order to use green surfactants. This adaptation will be extremely more efficient and possible with the results of DISFILM as a guideline.

1 415 506 €

Start date: 2017-09-01, End date: 2022-08-31

DREAM, Drafting and Enacting the Revolutions in the Arab Mediterranean, seeks to write the history of the revolutions in the Arab Mediterranean since the independences. It aims to write a transnational history of often forgotten struggles, recall facts and original forms of resistance. We know very few about the revolts that occurred in this period, and even less about the memory that they left in the societies, the way these memories circulated. This rediscovery of revolutions in the shadows must be done through the collection of original material, specifically “poor archives” of the ordinary and the production of Archives – through a combination of classical interviews and innovative methods that involve researchers, archivists, artists and the actors themselves. The objective is to write a history that focuses on emotions and paths of revolts, telling us more about the link between all dimensions of human lives in these territories (religion, gender, social positions) and the articulation of these dimensions in the revolutionary projects. DREAM aims to write a history that doesn’t produce heroes or big figures, doesn’t discuss success or failure, but tries to understand the motivations and the potentialities that were at stake in different episodes and moments, during the uprisings and in between them. It aims to explore the historical signification and the concrete aspects of the call for dignity (Karama/sharaf) in a space that, after liberating itself from the colonial domination, was trapped into the illusion of a common faith (being it the Arab nation or the Islamic umma) and the concrete oppression of authoritarian regimes. This period needs urgently to be explored and history, with its modern tools and patterns, can embrace and trace the particular conditions in which Arab people lived for more than six decades, and specifically the frames of their dreams and projections.

1 941 050 €

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

We propose to develop the theoretical foundations of transforming memory into data rates, and to explore their practical ramifications in wireless communication networks. Motivated by the long-lasting open challenge to invent a communication technology that scales with the network size, we have recently discovered early indications of how preemptive use of distributed data-storage at the receiving communication nodes (well before transmission), can offer unprecedented throughput gains by surprisingly bypassing the dreaded bottleneck of real-time channel-feedback. For an exploratory downlink configuration, we unearthed a hidden duality between feedback and preemptive use of memory, which managed to doubly-exponentially reduce the needed memory size, and consequently offered unbounded throughput gains compared to all existing solutions with the same resources. This was surprising because feedback and memory were thought to be mostly disconnected; one is used on the wireless PHY layer, the other on the wired MAC. This development prompts our key scientific challenge which is to pursue the mathematical convergence between feedback-information-theory and preemptive distributed data-storage, and to then design ultra-fast memory-aided communication algorithms that pass real-life testing. This is a structurally new approach, which promises to reveal deep links between feedback information theory and memory, for a variety of envisioned wireless-network architectures of exceptional promise. In doing so, our new proposed theory stands to identify the basic principles of how a splash of memory can surgically alter the informational-structure of these networks, rendering them faster, simpler and more efficient. In the end, this study has the potential to directly translate the continuously increasing data-storage capabilities, into gains of wireless network capacity, and to ultimately avert the looming network-overload caused by these same indefinite increases of data volumes.

1 978 778 €

Start date: 2017-04-01, End date: 2022-03-31

Nicotinic acetylcholine receptors (nAChRs) mediate neuronal synaptic transmission and modulation. They contribute to higher brain functions such as cognition and reward and are important drug targets. Recent studies have revealed that these acetylcholine-gated ion channels display an unanticipated conformational plasticity, adopting multiple allosteric states that shape the time course of their electrophysiological response. To date, a single nAChR structure has been solved at high resolution, and our understanding of the conformational transitions remains so far elusive. To address this challenge, we propose to develop a top-down approach starting from the study of the conformational transitions of nAChRs functionally expressed in cells, and then dissecting the molecular mechanisms on purified proteins. In WP1, we will develop an innovative fluorescence quenching approach to follow the protein motions concomitant with channel opening at the cell membrane. In WP2, we will further exploit this technique on purified proteins, to study the role/requirement of lipids, and their pharmacological crosstalk with allosteric modulators acting at the transmembrane domain. In WP3, the gained knowledge will open original routes to solve 3D structures of nAChRs, in novel conformations and in complex with allosteric modulators. The research will be centered on the major brain nAChRs, primarily the homomeric α7 and also the heteromeric α4β2 nAChRs that are major physiological players and key potential therapeutic targets. This multidisciplinary project combines electrophysiology, fluorescence, pharmacology, membrane protein biochemistry and structural biology, together with in silico modeling, molecular dynamics and ligand docking. The results will provide fundamental insights into the allosteric mechanisms underlying both nAChR function and its modulation by allosteric modulators that hold promises in therapeutics.

2 282 105 €

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

The ultimate goal of device miniaturization is to rely on a single charge provided by a single dopant atom: solotronics. Currently the gate length in a transistor cannot be reduced beyond 10-12 nm, as variability between nominally identical devices reaches unacceptable levels. Elaborate quantum transport experiments can monitor the presence and spin state of a single charge, but do not provide information about location and distribution (wavefunction) of the charge or the local chemical and crystallographic environment. The latter, however, determine why the charge is present at a specific location with a particular distribution. Scanning probe techniques can measure charges but are restricted to the near surface region. In contrast, the phase of an electron in transmission electron microscopy (TEM) can probe the sample volume and is sensitive to charge. The target of the e-See project is the first real time observation of the wavefunction associated to a single electron charge in the volume of a device with atomic resolution. I aim to implement low temperature quantum transport experiments in a TEM to allow simultaneous electrical manipulation of this charge. Combined visualization and manipulation of a single charge trapped by Coulomb blockade in a transistor will (i) identify the origins of device variability, and (ii) show how the local properties of the sample affect localization of a single charge and its wavefunction. The project impact involves understanding of variability, improving device design and creation of a new research field on low temperature electrical in situ TEM experiments. It will provide the tool to visualize a single charge wavefunction in any device, enabling ultimate device engineering: deterministic 3D atomic scale control of the position of charge localization. To this end, I will use electron holography and scanning TEM, develop a low temperature electrical TEM sample holder, and novel sample preparation.

1 998 958 €

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

Cardiac electrical diseases are directly responsible for sudden cardiac death, heart failure and stroke. They result from a complex interplay between myocardial electrical activation and structural heterogeneity. Current diagnostic strategy based on separate electrocardiographic and imaging assessment is unable to grasp both these aspects. Improvements in personalised diagnostics are urgently needed as existing curative or preventive therapies (catheter ablation, multisite pacing, and implantable defibrillators) cannot be offered until patients are correctly recognised. My aim is to achieve a major advance in the way cardiac electrical diseases are characterised and thus diagnosed and treated, through the development of a novel non-invasive modality (Electrostructural Tomography), combining magnetic resonance imaging (MRI) and non-invasive cardiac mapping (NIM) technologies. The approach will consist of: (1) hybridising NIM and MRI technologies to enable the joint acquisition of magnetic resonance images of the heart and torso and of a large array of body surface potentials within a single environment; (2) personalising the inverse problem of electrocardiography based on MRI characteristics within the heart and torso, to enable accurate reconstruction of cardiac electrophysiological maps from body surface potentials within the 3D cardiac tissue; and (3) developing a novel disease characterisation framework based on registered non-invasive imaging and electrophysiological data, and propose novel diagnostic and prognostic markers. This project will dramatically impact the tailored management of cardiac electrical disorders, with applications for diagnosis, risk stratification/patient selection and guidance of pacing and catheter ablation therapies. It will bridge two medical fields (cardiac electrophysiology and imaging), thereby creating a new research area and a novel semiology with the potential to modify the existing classification of cardiac electrical diseases.

1 475 000 €

Start date: 2017-02-01, End date: 2022-01-31

Evolutionary and ecological processes can affect one another. For example, adaptation can affect population dynamics or species interactions in communities, and thus ecosystem functioning. Eco-evolutionary systems show periods of both stability and of sudden change, but the following general hypotheses for the causes of these complex dynamics are largely untested in natural settings. First, eco-evolutionary systems are thought to be governed by feedback loops, with positive feedback promoting rapid change and negative feedback stabilising dynamics. However, drivers with one-way effects likely also contribute, such as sudden environmental changes or mutations that do not interact with other genetic loci. Second, the capacity of meta-populations or communities to recover from disturbance (i.e., their resilience) can be affected by connectivity, with high connectivity making a system buffered and resilient to local change, but prone to system-wide change. Our understanding of how eco-evolutionary systems respond to environmental change will remain fundamentally limited until these hypotheses receive focused tests. This proposal outlines field-based, experimental, genomic, and model-based tests of these hypotheses, and also tests theories for the maintenance of genetic variation and the genetic basis of adaptation. The work uses meta-populations of Timema stick insects on different host plants and their associated arthropod communities. It tests how adaptation within species affects ecological dynamics across levels of biological organisation ranging from populations to ecosystems. It is novel via examining causal associations between ecology and evolution in nature, in light of theoretical predictions concerning feedback and connectivity. The results could help transform our understanding of complex systems in ecology, evolution, and beyond.

1 990 734 €

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

Navigation is one of the most crucial and most challenging problems animals face. Behavioural analyses have shown that animals make use of a number of different mechanisms to navigate, but very little is known of how spatial information is processed and integrated by the brain. This project will exploit the stunning ability of ants in learning long visual routes to investigate the mechanisms of navigation in a brain numerically much simpler than vertebrate. We will combine an ecological approach with state-of-the-art technologies to enable a thorough control of sensory-motor cues while the ant is navigating in virtual-reality reconstructions of its natural environments. This new and powerful method will enable us to dissect the mechanisms underlying the emergence of navigational behaviours by performing straightforward manipulations. The results will be modelled in the light of insect neurobiology and integrated into an increasingly complete neural architecture. This neural architecture will be embedded into an agent navigating in the same virtual-reality environment as the real ants for testing. The advantage of such an inter-disciplinary approach is that failures of our agent will help us identify gaps in our knowledge and thus fuel new experimentation. Reciprocally, our agent will become increasingly refined in the light of incoming experimental results. This will create a positive feedback towards a complete, multi-level understanding of navigation in the wild. The findings will inspire new robust solutions for navigational problems that can be applied to bio-robotics.

1 439 893 €

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

Understanding the links between neuronal plasticity which underlies memory and energy metabolism is a major goal of brain studies. The brain is a main energy consumer and the central regulator of energy homeostasis, and it prioritizes its own supply over peripheral organs. Interestingly, our work demonstrates that the brain is also able to regulate its own activity under energy shortage to favor survival. The EnergyMemo project proposes to perform in drosophila an original integrated study of the interplay between energy metabolism and olfactory memory at the molecular, cellular and circuit levels. On the ground of important preliminary results, we will investigate in vivo how and why the energy flux increases during long-term memory encoding, and how brain plasticity is regulated by the energy supply. We will focus on three major challenges: * Objective 1: to improve our understanding of brain physiology, we will characterize in drosophila neuronal circuits that integrate information about the brain energy status. * Objective 2: to understand how abnormal levels of energy can affect the brain, we will analyze how the energy level shapes the functioning of the olfactory memory center. * Objective 3: to characterize how energy stores are mobilized during memory formation, we will investigate how the neuronal and glial networks interact to manage the energy fluxes. This multidisciplinary project will benefit from our team's longstanding experience in behavioral studies and leadership in live brain imaging, in addition to the unmatched descriptive power of drosophila neuronal circuits at the single-neuron resolution. Successful completion of this program will surely uncover mechanisms of brain function conserved across species, and should bring-up new ideas about how deregulation of energy metabolism can affect cognitive functions in human. Thus the EnergyMemo project could have a major impact in neuroscience from fundamental research to human applications.

2 499 500 €

Start date: 2017-10-01, End date: 2022-09-30

The immune system uses both short- and long-range communication mechanisms to mount the coordinated and sophisticated cellular responses required to control microbial infections or fight tumors. Yet, our understanding of how immunological signals are integrated and propagated by individual cells in complex tissue microenvironments remains largely limited. ENLIGHTEN is a research program dedicated to establish new mechanisms by which the immune system fight tumors or infections, based on the direct manipulation of immunological signals in vivo. In relevant mouse models of human disease, we will combine intravital imaging, fluorescent sensors and optogenetic actuators to control single cell functions in real-time. We wish to understand how T cells sense and interpret cell-contacts in lymphoid organs and in developing tumors at steady state or during immunotherapy. In addition, we aim to establish how cytokine and chemokine gradients form in tissues and are interpreted by immune cells during infection or cancer. By determining the functional contribution of single immune cells in vivo, we aim to identify new paradigms for information transfer in the immune system during cancer or infection and to establish the combination of optogenetics and intravital imaging as a powerful strategy for decoding immune reactions in the context of disease pathogenesis.

2 499 994 €

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

General relativity has been introduced by A. Einstein in 1915. It is a major theory of modern physics and at the same time has led to fascinating mathematical problems. The present proposal focusses on two aspects of the evolution problem for the Einstein equations which has been initiated by the pioneering work of Y. Choquet-Bruhat in 1952. The Einstein equations form a nonlinear system of partial differential equations of hyperbolic type whose complexity raises significant challenges to its mathematical analysis. The goal of this project is to strengthen our understanding of two important themes concerning the evolution problem in general relativity. On the one hand, the control of low regularity solutions of the Einstein equations, a topic which is intimately linked with the celebrated cosmic censorship conjectures of R. Penrose, a major open problem in the field. On the other hand, the question of the stability of particular solutions of the Einstein equations in the wake of the groundbreaking proof of the stability of the Minkowski space-time due to D. Christodoulou and S. Klainerman. These directions are extremely active and have recently led to impressive results. More specifically, this project proposes to consider the following two work packages -Going beyond the bounded L2 curvature theorem. This result has been recently obtained by the PI in collaboration with S. Klainerman and I. Rodnianski and is the sharpest result in so far as low regularity solutions of the Einstein equations are concerned. Yet, the fundamental quest towards a scale invariant well-posedness criterion for the Einstein equations remains wide open. -The black hole stability problem. This problem concerns the stability of the Kerr metrics which form a 2-parameter family of solutions to the Einstein vacuum equations. Many results have been obtained concerning various versions of linear stability, but significant challenges remain in order to tackle the nonlinear stability result.

1 455 000 €

Start date: 2017-05-01, End date: 2022-04-30

Obesity is associated with adipose tissue dysfunction leading to the onset of several pathologies including type 2 diabetes (T2D). The mechanisms underlying the development of obesity and T2D include the hypertrophy and/or hyperplasia of adipocytes and adipose tissue inflammation together with an altered secretion of adipokines. However, the explanation of why individual obese (and some non-obese) humans differ in their susceptibility to develop T2D is still an issue that is currently not sufficiently addressed. This susceptibility to T2D is mainly associated with environmental factors. One link between environment and disease is epigenetics influencing gene expression and subsequently organ dysfunction. Epigenetic modifications in adipose tissue have been proposed to influence the susceptibility to T2D. However, the epigenomic mechanisms underpinning adipose tissue dysfunction are poorly known. In search for epigenomic modifiers that control adipose tissue function and also impact on T2D pathogenesis, we have recently identified the transcriptional coregulators GPS2 (G-Protein Pathway Suppressor 2) and KDM6B (Histone Lysine Demethylase 6B, also called JMJD3) as strong candidates. Our hypothesis is that the clinically documented dysregulation of GPS2 (down) and KDM6B (up) expression and function during obesity leads to the closely linked epigenetic and transcriptional reprogramming of adipocytes and adipose tissue-macrophages, thereby enhancing the susceptibility to metabolic and inflammatory disturbances and the progression towards T2D. We propose here to test this hypothesis using the combination of unique mouse models, genome-wide molecular and epigenomic analyses and human studies to dissect the epigenomic functions of GPS2 and KDM6B in adipose tissue, aiming at identifying mechanism involved in the development T2D. Thereby, we anticipate the discovery of novel epigenomic targets for future prevention and treatment strategies in metabolic dysfunction.

2 000 000 €

Start date: 2017-06-01, End date: 2022-05-31

Economics provides decision-makers with powerful tools to analyse a wide range of issues. The methodological unity of the discipline and its quest for a general understanding of market as well as non-market interactions have given the discipline great influence on policy. A core component of economics is its assumption that individuals act as if they each had some goal function that they seek to maximise, under the constraints they face and the information they have. Despite significant advances in behavioural economics, there still is no consensus as to whether and why certain preferences are more likely than others. Further progress could be made if the factors that shape human motivation in the first place were understood. The aim of this project is to produce novel insights about such factors, by establishing evolutionary foundations of human motivation.The project's scope is ambitious. First, it will study two large classes of interactions: strategic interactions, and interactions within the realm of the family. Second, to obtain both depth and breadth of insights, it will consist of four different, but inter-related, components (three theoretical and one empirical), the ultimate goal being to significantly enhance our overall understanding of the factors that shape human motivation. The methodology is ground-breaking in that it is strongly interdisciplinary. Parts of the body of knowledge built by biologists and evolutionary anthropologists in the past decades will be combined with state-of-the-art economics to produce insights that cannot be obtained within any single discipline. Focus will nonetheless be on addressing issues of importance for economists.The proposed research builds on extensive work done by the PI in the past decade. It will benefit from the years that the PI has invested in understanding the biology and the evolutionary anthropology literatures, and in contributing towards building an interdisciplinary research ecosystem in Toulouse, France

1 550 891 €

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

We propose to lay the theoretical foundations and design efficient computational methods for analyzing, quantifying and exploring relations and variability in structured data sets, such as collections of geometric shapes, point clouds, and large networks or graphs, among others. Unlike existing methods that are tied and often limited to the underlying data representation, our goal is to design a unified framework in which variability can be processed in a way that is largely agnostic to the underlying data type. In particular, we propose to depart from the standard representations of objects as collections of primitives, such as points or triangles, and instead to treat them as functional spaces that can be easily manipulated and analyzed. Since real-valued functions can be defined on a wide variety of data representations and as they enjoy a rich algebraic structure, such an approach can provide a completely novel unified framework for representing and processing different types of data. Key to our study will be the exploration of relations and variability between objects, which can be expressed as operators acting on functions and thus treated and analyzed as objects in their own right using the vast number of tools from functional analysis in theory and numerical linear algebra in practice. Such a unified computational framework of variability will enable entirely novel applications including accurate shape matching, efficiently tracking and highlighting most relevant changes in evolving systems, such as dynamic graphs, and analysis of shape collections. Thus, it will permit not only to compare or cluster objects, but also to reveal where and how they are different and what makes instances unique, which can be especially useful in medical imaging applications. Ultimately, we expect our study to create to a new rigorous, unified paradigm for computational variability, providing a common language and sets of tools applicable across diverse underlying domains.

1 499 845 €

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

Despite the dramatic impact of earthquakes, the physics of their onset and the short-term behavior of fault are still poorly understood. Using existing high quality seismic observations, we propose to develop a novel functional imaging of the brittle crust to clarify not only structural properties but also the dynamics of faults. We will analyze spatio-temporal changes of elastic properties around fault zones to highlight the interplay between changes in the host rocks and fault slip. Imaging the damage structure around faults and its evolution requires new seismological methods. With novel methods to image the highly heterogeneous fault regions, we will provide multi-scale descriptions of fault zones, including their laterally variable thicknesses and depth dependence. In parallel we will image temporal changes of seismic velocities and scattering strength. External natural forcing terms (e.g. tides, seasonal hydrologic loadings) will be modeled to isolate the signals of tectonic origin. This will also allow us to monitor the evolving seismic susceptibility, i.e. a measure of the proximity to a critical state of failure. Improved earthquake detection techniques using ‘deep machine learning’ methods will facilitate tracking the evolution of rock damage. The imaging and monitoring will provide time-lapse images of elastic moduli, susceptibility and seismicity. The observed short-time changes of the materials will be included in slip initiation models coupling the weakening of both the friction and the damaged host rocks. Laboratory experiments will shed light on the transition of behavior from granular (shallow fault core) to cohesive (distant host rock) materials. Our initial data cover two well-studied fault regions of high earthquake probability (Southern California and the Marmara region, Turkey) and an area of induced seismicity (Groningen). The derived results and new versatile imaging and monitoring techniques can have fundamental social and economic impacts.

2 434 743 €

Start date: 2017-10-01, End date: 2022-09-30

Many mechanical structures are submitted to repeated loadings and can break under stress lower than the ultimate tensile stress. This phenomenon is called the fatigue of materials and can be found in many industrial sectors, such as the transport industry, aeronautic industry and energy production. Fatigue design is thus crucial in engineering and it requires the precise characterization of material behavior under cyclic loadings to ensure the safety and reliability of structures throughout their life. An increase in the life span of a structure or a reduction in the number of maintenance phases leads to an increases in the number of cycles applied to this structure. It is presently common to find mechanical systems subjected to several billion cycles, in what is called the gigacycle fatigue domain. The characterization of the fatigue behavior of materials requires fatigue tests to be conducted until fracture for different stress amplitudes. One problem with this method is the test duration, which becomes excessive and beyond possible, particularly for a very high number of cycles. The goal of FastMat is to develop a new method that reduces considerably the duration of fatigue characterization. This method involves the use of only short interrupted tests coupled with a self-heating measurement to characterize the fatigue behavior for very low stress amplitudes. The scientific objective is to develop simultaneously experimental and numerical tools for the fast determination of fatigue behavior. The experimental approach will be developed to estimate simultaneously the dissipation and the stored energy, which directly reflect fatigue damage. For the numerical approach, discrete dislocation dynamics simulations will be developed to establish links between the fatigue damage associated with the evolution of dislocation structures, the stored energy and the dissipated energy.

1 860 963 €

Start date: 2017-07-01, End date: 2022-06-30