ERC FUNDED PROJECTS

This project aims at promoting sustainable combustion technologies for transport via validation of advanced combustion kinetic models obtained using sophisticated new laboratory experiments, engines, and theoretical computations, breaking through the current frontier of knowledge. It will focus on the unexplored kinetics of ignition and combustion of 2nd generation (2G) biofuels and blends with conventional fuels, which should provide energy safety and sustainability to Europe. The motivation is that no accurate kinetic models are available for the ignition, oxidation and combustion of 2G-biofuels, and improved ignition control is needed for new compression ignition engines. Crucial information is missing: data from well characterised experiments on combustion-generated pollutants and data on key-intermediates for fuels ignition in new engines. To provide that knowledge new well-instrumented complementary experiments and kinetic modelling will be used. Measurements of key-intermediates, stables species, and pollutants will be performed. New ignition control strategies will be designed, opening new technological horizons. Kinetic modelling will be used for rationalising the results. Due to the complexity of 2G-biofuels and their unusual composition, innovative surrogates will be designed. Kinetic models for surrogate fuels will be generalised for extension to other compounds. The experimental results, together with ab-initio and detailed modelling, will serve to characterise the kinetics of ignition, combustion, and pollutants formation of fuels including 2G biofuels, and provide relevant data and models. This research is risky because this is (i) the 1st effort to measure radicals by reactor/CRDS coupling, (ii) the 1st effort to use a μ-channel reactor to build ignition databases for conventional and bio-fuels, (iii) the 1st effort to design and use controlled generation and injection of reactive species to control ignition/combustion in compression ignition engines

2 498 450 €

Start date: 2011-12-01, End date: 2016-11-30

Several observed anomalies in neutrino oscillation data can be explained by a hypothetical fourth neutrino separated from the three standard neutrinos by a squared mass difference of a few eV2. This hypothesis can be tested with a PBq (ten kilocurie scale) 144Ce antineutrino beta-source deployed at the center of a large low background liquid scintillator detector, such like Borexino, KamLAND, and SNO+. In particular, the compact size of such a source could yield an energy-dependent oscillating pattern in event spatial distribution that would unambiguously determine neutrino mass differences and mixing angles. The proposed program aims to perform the necessary research and developments to produce and deploy an intense antineutrino source in a large liquid scintillator detector. Our program will address the definition of the production process of the neutrino source as well as its experimental characterization, the detailed physics simulation of both signal and backgrounds, the complete design and the realization of the thick shielding, the preparation of the interfaces with the antineutrino detector, including the safety and security aspects.

1 500 000 €

Start date: 2012-10-01, End date: 2018-09-30

What is responsible for the emergence of homochirality, the almost exclusive use of one enantiomer over its mirror image? And what led to the evolution of life’s homochiral biopolymers, DNA/RNA, proteins and lipids, where all the constituent monomers exhibit the same handedness? Based on in-situ observations and laboratory studies, we propose that this handedness occurs when chiral biomolecules are synthesized asymmetrically through interaction with circularly polarized photons in interstellar space. The ultimate goal of this project will be to demonstrate how the diverse set of heterogeneous enantioenriched molecules, available from meteoritic impact, assembles into homochiral pre-biopolymers, by simulating the evolutionary stages on early Earth. My recent research has shown that the central chiral unit of RNA, ribose, forms readily under simulated comet conditions and this has provided valuable new insights into the accessibility of precursors of genetic material in interstellar environments. The significance of this project arises due to the current lack of experimental demonstration that amino acids, sugars and lipids can simultaneously and asymmetrically be synthesized by a universal physical selection process. A synergistic methodology will be developed to build a unified theory for the origin of all chiral biological building blocks and their assembly into homochiral supramolecular entities. For the first time, advanced analyses of astrophysical-relevant samples, asymmetric photochemistry triggered by circularly polarized synchrotron and laser sources, and chiral amplification due to polymerization processes will be combined. Intermediates and autocatalytic reaction kinetics will be monitored and supported by quantum calculations to understand the underlying processes. A unified theory on the asymmetric formation and self-assembly of life’s biopolymers is groundbreaking and will impact the whole conceptual foundation of the origin of life.

1 500 000 €

Start date: 2019-04-01, End date: 2024-03-31

The primary purpose of this project is to build on recent spectacular progress in the Langlands program to study the arithmetic properties of automorphic motives constructed in the cohomology of Shimura varieties. Because automorphic methods are available to study the L-functions of these motives, which include elliptic curves and certain families of Calabi-Yau varieties over totally real fields (possibly after base change), they represent the most accessible class of varieties for which one can hope to verify fundamental conjectures on special values of L-functions, including Deligne's conjecture and the Main Conjecture of Iwasawa theory. Immediate goals include the proof of irreducibility of automorphic Galois representations; the establishment of period relations for automorphic and potentially automorphic realizations of motives in the cohomology of distinct Shimura varieties; the construction of p-adic L-functions for these and related motives, notably adjoint and tensor product L-functions in p-adic families; and the geometrization of the p-adic and mod p Langlands program. All four goals, as well as the others mentioned in the body of the proposal, are interconnected; the final goal provides a bridge to related work in geometric representation theory, algebraic geometry, and mathematical physics.

1 491 348 €

Start date: 2012-06-01, End date: 2018-05-31

Actanthrope intends to promote a neuro-robotics perspective to explore original models of anthropomorphic action. The project targets contributions to humanoid robot autonomy (for rescue and service robotics), to advanced human body simulation (for applications in ergonomics), and to a new theory of embodied intelligence (by promoting a motion-based semiotics of the human action). Actions take place in the physical space while they originate in the –robot or human– sensory-motor space. Geometry is the core abstraction that makes the link between these spaces. Considering that the structure of actions inherits from that of the body, the underlying intuition is that actions can be segmented within discrete sub-spaces lying in the entire continuous posture space. Such sub-spaces are viewed as symbols bridging deliberative reasoning and reactive control. Actanthrope argues that geometric approaches to motion segmentation and generation as promising and innovative routes to explore embodied intelligence: - Motion segmentation: what are the sub-manifolds that define the structure of a given action? - Motion generation: among all the solution paths within a given sub-manifold, what is the underlying law that makes the selection? In Robotics these questions are related to the competition between abstract symbol manipulation and physical signal processing. In Computational Neuroscience the questions refer to the quest of motion invariants. The ambition of the project is to promote a dual perspective: exploring the computational foundations of human action to make better robots, while simultaneously doing better robotics to better understand human action. A unique “Anthropomorphic Action Factory” supports the methodology. It aims at attracting to a single lab, researchers with complementary know-how and solid mathematical background. All of them will benefit from unique equipments, while being stimulated by four challenges dealing with locomotion and manipulation actions.

2 500 000 €

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

"Computer vision is concerned with the automated interpretation of images and video streams. Today's research is (mostly) aimed at answering queries such as ""Is this a picture of a dog?"", (classification) or sometimes ""Find the dog in this photo"" (detection). While categorisation and detection are useful for many tasks, inferring correct class labels is not the final answer to visual recognition. The categories and locations of objects do not provide direct understanding of their function i.e., how things work, what they can be used for, or how they can act and react. Such an understanding, however, would be highly desirable to answer currently unsolvable queries such as ""Am I in danger?"" or ""What can happen in this scene?"". Solving such queries is the aim of this proposal. My goal is to uncover the functional properties of objects and the purpose of actions by addressing visual recognition from a different and yet unexplored perspective. The main novelty of this proposal is to leverage observations of people, i.e., their actions and interactions to automatically learn the use, the purpose and the function of objects and scenes from visual data. The project is timely as it builds upon the two key recent technological advances: (a) the immense progress in visual recognition of objects, scenes and human actions achieved in the last ten years, as well as (b) the emergence of a massive amount of public image and video data now available to train visual models. ACTIVIA addresses fundamental research issues in automated interpretation of dynamic visual scenes, but its results are expected to serve as a basis for ground-breaking technological advances in practical applications. The recognition of functional properties and intentions as explored in this project will directly support high-impact applications such as detection of abnormal events, which are likely to revolutionise today's approaches to crime protection, hazard prevention, elderly care, and many others."

1 497 420 €

Start date: 2013-01-01, End date: 2018-12-31

"During the twentieth century, the development of macroscopic engineering has been largely stimulated by progress in digital prototyping: cars, planes, boats, etc. are nowadays designed and tested on computers. Digital prototypes have progressively replaced actual ones, and effective computer-aided engineering tools have helped cut costs and reduce production cycles of these macroscopic systems. The twenty-first century is most likely to see a similar development at the atomic scale. Indeed, the recent years have seen tremendous progress in nanotechnology - in particular in the ability to control matter at the atomic scale. Similar to what has happened with macroscopic engineering, powerful and generic computational tools will be needed to engineer complex nanosystems, through modeling and simulation. As a result, a major challenge is to develop efficient simulation methods and algorithms. NANO-D, the INRIA research group I started in January 2008 in Grenoble, France, aims at developing efficient computational methods for modeling and simulating complex nanosystems, both natural and artificial. In particular, NANO-D develops SAMSON, a software application which gathers all algorithms designed by the group and its collaborators (SAMSON: Software for Adaptive Modeling and Simulation Of Nanosystems). In this project, I propose to develop a unified theory, and associated algorithms, for adaptive particle simulation. The proposed theory will avoid problems that plague current popular multi-scale or hybrid simulation approaches by simulating a single potential throughout the system, while allowing users to finely trade precision for computational speed. I believe the full development of the adaptive particle simulation theory will have an important impact on current modeling and simulation practices, and will enable practical design of complex nanosystems on desktop computers, which should significantly boost the emergence of generic nano-engineering."

1 476 882 €

Start date: 2012-09-01, End date: 2017-08-31

The aim of this project is the realisation of efficient mid-infrared and THz optoelectronic emitters. This work is motivated by the fact that the spontaneous emission in this frequency range is characterized by an extremely long lifetime when compared to non-radiative processes, giving rise to devices with very low quantum efficiency. To this end we want to develop hybrid light-matter systems, already well known in quantum optics, within optoelectronics devices, that will be driven by electrical injection. With this project we want to extend the field of optoelectronics by introducing some of the concepts of quantum optic, particularly the light-matter strong coupling, into semiconductor devices. More precisely this project aims at the implementation of novel optoelectronic emitters operating in the strong coupling regime between an intersubband excitation of a two-dimensional electron gas and a microcavity photonic mode. The quasiparticles issued from this coupling are called intersubband polaritons. The major difficulties and challenges of this project, do not lay in the observation of these quantum effects, but in their exploitation for a specific function, in particular an efficient electrical to optical conversion. To obtain efficient quantum emitters in the THz frequency range we will follow two different approaches: - In the first case we will try to exploit the additional characteristic time of the system introduced by the light-matter interaction in the strong (or ultra-strong) coupling regime. - The second approach will exploit the fact that, under certain conditions, intersubband polaritons have a bosonic character; as a consequence they can undergo stimulated scattering, giving rise to polaritons lasers as it has been shown for excitonic polaritons.

1 761 000 €

Start date: 2010-05-01, End date: 2015-04-30

AMPA glutamate receptors (AMPAR) play key roles in information processing by the brain as they mediate nearly all fast excitatory synaptic transmission. Their spatio-temporal organization in the post synapse with respect to presynaptic glutamate release sites is a key determinant in synaptic transmission. The activity-dependent regulation of AMPAR organization is at the heart of synaptic plasticity processes underlying learning and memory. Dysfunction of synaptic transmission - hence AMPAR organization - is likely at the origin of a number of brain diseases. Building on discoveries made during my past ERC grant, our new ground-breaking objective is to uncover the mechanisms that link synaptic transmission with the dynamic organization of AMPAR and associated proteins. For this aim, we have assembled a team of neurobiologists, computer scientists and chemists with a track record of collaboration. We will combine physiology, cellular and molecular neurobiology with development of novel quantitative imaging and biomolecular tools to probe the molecular dynamics that regulate synaptic transmission. Live high content 3D SuperResolution Light Imaging (SRLI) combined with electron microscopy will allow unprecedented visualization of AMPAR organization in synapses at the scale of individual subunits up to the level of intact tissue. Simultaneous SRLI and electrophysiology will elucidate the intricate relations between dynamic AMPAR organization, trafficking and synaptic transmission. Novel peptide- and small protein-based probes used as protein-protein interaction reporters and modulators will be developed to image and directly interfere with synapse organization. We will identify new processes that are fundamental to activity dependent modifications of synaptic transmission. We will apply the above findings to understand the causes of early cognitive deficits in models of neurodegenerative disorders and open new avenues of research for innovative therapies.

2 491 157 €

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

The scientific motivation of this project is the significant presence of organic compounds at the surface of the ocean. They form the link between ocean biogeochemistry through the physico-chemical processes near the water-air interface with primary and secondary aerosol formation and evolution in the air aloft and finally to the climate impact of marine boundary layer aerosols. However, their photochemistry and photosensitizer properties have only been suggested and discussed but never fully addressed because they were beyond reach. This project suggests going significantly beyond this matter of fact by a combination of innovative tools and the development of new ideas. This project is therefore devoted to new laboratory investigations of processes occurring at the air sea interface to predict emission, formation and evolution of halogenated radicals and aerosols from this vast interface between oceans and atmosphere. It progresses from fundamental laboratory measurements, marine science, surface chemistry, photochemistry … and is therefore interdisciplinary in nature. It will lead to the development of innovative techniques for characterising chemical processing at the air sea interface (e.g., a multiphase atmospheric simulation chamber, a time-resolved fluorescence technique for characterising chemical processing at the air-sea interface). It will allow the assessment of new emerging ideas such as a quantitative description of the importance of photosensitized reactions in the visible at the air/sea interface as a major source of halogenated radicals and aerosols in the marine environment. This new understanding will impact on our ability to describe atmospheric chemistry in the marine environment which has strong impact on the urban air quality of coastal regions (which by the way represent highly populated regions ) but also on climate change by providing new input for global climate models.

2 366 276 €

Start date: 2012-04-01, End date: 2017-03-31

The goal of this PoC proposal is to boost the creation of a start-up (AllYours) targeting both Internet users as well as small to medium companies (SME) offering full-fledged personalization in notification systems. The Web is now all about users; they are the greediest bandwidth consumers, the ultimate deciders of which applications are actually adopted and also the most prolific content generators. While social networks have taken off at an unexpected scale and speed, Web navigation has radically changed to the point that notification is taking over search: many users now navigate through the links they discover rather than explicit search operations. Yet, users get quickly overwhelmed with the huge amount of information in a click range. For such notification systems to be truly useful, they should be personalized depending on the user activity, operations, posts, interests. Yet, personalization poses several issues such as scalability (it is expensive to store a large amount of information per user) and privacy (users are more and more reluctant to give away their preferences to large companies). At the same time, SMEs are struggling to provide fully personalized services given the expertise and amount of resources such algorithms require. AllYours is an implicit instant item recommender providing personalization in the notification process without requiring explicit subscriptions to feeds or interests. They only let the system know whether they like the items received or not (eg like/dislike button). In addition, users personal data are stored on their own machine, leaving the space to provide a wide spectrum of privacy guarantees while enabling cross application benefits. Behind the scene, AllYours provides each user with a live social network of participants sharing similar interests, called an implicit social network. AllYours come in two different flavors: (1) Enterprise-AllYours provides a scalable notification and recommendation system targeting all SMEs operating Web content editors & ecommerce sites (2) P2P-AllYours provides a fully decentralized solution without requiring users to ever reveal their private preferences through a clever obfuscation mechanism.

149 236 €

Start date: 2013-01-01, End date: 2013-12-31

One already available method to expand the range of material properties is to adjust the composition of materials at the molecular level using chemistry. We would like to develop the alternative approach of homogenization which broadens the definition of a material to include artificially structured media (fluids and solids) in which the effective electromagnetic, hydrodynamic or elastic responses result from a macroscopic patterning or arrangement of two or more distinct materials. This project will explore the latter avenue in order to markedly enhance control of surface water waves and elastodynamic waves propagating within artificially structured fluids and solid materials, thereafter called acoustic metamaterials. Pendry's perfect lens, the paradigm of electromagnetic metamaterials, is a slab of negative refractive index material that takes rays of light and causes them to converge with unprecedented resolution. This flat lens is a combination of periodically arranged resonant electric and magnetic elements. We will draw systematic analogies with resonant mechanical systems in order to achieve similar control of hydrodynamic and elastic waves. This will allow us to extend the design of metamaterials to acoustics to go beyond the scope of Snell-Descartes' laws of optics and Newton's laws of mechanics. Acoustic metamaterials allow the construction of invisibility cloaks for non-linear surface water waves (e.g. tsunamis) propagating in structured fluids, as well as seismic waves propagating in thin structured elastic plates. Maritime and civil engineering applications are in the protection of harbours, off-shore platforms and anti-earthquake passive systems. Acoustic cloaks for an enhanced control of pressure waves in fluids will be also designed for underwater camouflaging. Light and sound interplay will be finally analysed in order to design controllable metamaterials with a special emphasis on undetectable microstructured fibres (acoustic wormholes).

1 280 391 €

Start date: 2011-10-01, End date: 2016-09-30

Malaria parasite infection in humans has been called “the strongest known force for evolutionary selection in the recent history of the human genome”, and I hypothesize that a similar statement may apply to the mosquito vector, which is the definitive host of the malaria parasite. We previously discovered efficient malaria-resistance mechanisms in natural populations of the African malaria vector, Anopheles gambiae. Aim 1 of the proposed project will implement a novel genetic mapping design to systematically survey the mosquito population for common and rare genetic variants of strong effect against the human malaria parasite, Plasmodium falciparum. A product of the mapping design will be living mosquito families carrying the resistance loci. Aim 2 will use the segregating families to functionally dissect the underlying molecular mechanisms controlled by the loci, including determination of the pathogen specificity spectra of the host-defense traits. Aim 3 targets arbovirus transmission, where Anopheles mosquitoes transmit human malaria but not arboviruses such as Dengue and Chikungunya, even though the two mosquitoes bite the same people and are exposed to the same pathogens, often in malaria-arbovirus co-infections. We will use deep-sequencing to detect processing of the arbovirus dsRNA intermediates of replication produced by the RNAi pathway of the mosquitoes. The results will reveal important new information about differences in the efficiency and quality of the RNAi response between mosquitoes, which is likely to underlie at least part of the host specificity of arbovirus transmission. The 3 Aims will make significant contributions to understanding malaria and arbovirus transmission, major global public health problems, will aid the development of a next generation of vector surveillance and control tools, and will produce a definitive description of the major genetic factors influencing host-pathogen interactions in mosquito immunity.

2 307 800 €

Start date: 2013-03-01, End date: 2018-02-28

RNA interference (RNAi) is a conserved sequence-specific, gene-silencing mechanism that is induced by double-stranded RNA (dsRNA). One of the functions of this pathway is the defense against parasitic nucleic acids: transposons and viruses. Previous results demonstrated that viral infections in Drosophila melanogaster are fought by an antiviral RNAi response and that components of the endocytic pathway are required for dsRNA entry to initiate the RNAi response. Recently we have shown that infected insect cells spread a systemic silencing signal that elicits a protective RNAi-dependent immunity throughout the organism. This suggests that the cell-autonomous RNAi response is insufficient to control a viral infection and that flies also rely on systemic immune response to fight against such infections. As a junior group leader, I will study the mechanisms that mediate the RNAi-based antiviral response in insects. By combining biochemical, cellular, molecular and genomic approaches, both in vivo and in cell culture, I will analyze the mechanisms underlying viral tropism, systemic propagation of the antiviral signal and the basis of the persistence of the antiviral state. Furthermore, I will examine whether the dsRNA-uptake pathway is conserved in mosquitoes and its relationship with viral immunity in that host. This comprehensive approach will tackle how this nucleic acid-based immunity works in insects to generate an anti-viral stage. A better understanding of the role of RNA silencing in insects during virus infection will allow the exploitation of this pathway for improvement of public health related problems such as arbovirus infection and disease.

1 900 000 €

Start date: 2009-10-01, End date: 2014-12-31

Arboviruses infect millions of people each year, however, mechanisms that drive viral emergence and maintenance remain largely unknown. A combination of host factors (e.g., human mobility), mosquito factors (e.g., abundance) and viral factors (e.g., transmissibility) interconnect to drive spread. Further, for endemic arboviruses, complex patterns of population immunity, built up over many years, appear key to the emergence of particular lineages. To disentangle the contribution of these different drivers, we need detailed data from the same pathogen system over a long time period from the same location. In addition, we need new methods, which can integrate these different data sources and allow appropriate mechanistic inferences. In this project, I will use the most globally prevalent arbovirus, dengue virus, as a case study. I will focus on Thailand where all four dengue serotypes have circulated endemically for decades and excellent long-term data and isolates exist, to address two fundamental questions: i) How do population-level patterns of immunity evolve over time and what is their impact on strain dynamics? I will use mechanistic models applied to historic serotype-specific case data to reconstruct the evolving immune profile of the population and explore the impact of immunity on viral diversity using sequences from archived isolates from each year over a 50-year period. ii) How do human behaviors, vector densities interact with immunity to dictate spread? I will work with geolocated full genome sequences from across Thailand and use detailed data on how people move, their contact patterns, their immunity profiles and mosquito distributions to study competing hypotheses of how arboviruses spread. I will compare the key drivers of dengue spread with that found for outbreaks of Zika and chikungunya. This proposal addresses fundamental questions about the mechanisms that drive arboviral emergence and spread that will be relevant across disease systems.

1 499 896 €

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

The goal of this project is to prepare in a deterministic way, and then to characterize, various entangled states of up to 25 individual atoms held in an array of optical tweezers. Such a system provides a new arena to explore quantum entangled states of a large number of particles. Entanglement is the existence of quantum correlations between different parts of a system, and it is recognized as an essential property that distinguishes the quantum and the classical worlds. It is also a resource in various areas of physics, such as quantum information processing, quantum metrology, correlated quantum systems and quantum simulation. In the proposed design, each site is individually addressable, which enables single atom manipulation and detection. This will provide the largest entangled state ever produced and fully characterized at the individual particle level. The experiment will be implemented by combining two crucial novel features, that I was able to demonstrate very recently: first, the manipulation of quantum bits written on long-lived hyperfine ground states of single ultra-cold atoms trapped in microscopic optical tweezers; second, the generation of entanglement by using the strong long-range interactions between Rydberg states. These interactions lead to the so-called dipole blockade , and enable the preparation of various classes of entangled states, such as states carrying only one excitation (W states), and states analogous to Schrödinger s cats (GHZ states). Finally, I will also explore strategies to protect these states against decoherence, developed in the framework of fault-tolerant and topological quantum computing. This project therefore combines an experimental challenge and the exploration of entanglement in a mesoscopic system.

1 449 600 €

Start date: 2009-12-01, End date: 2014-11-30

We propose to investigate a new frontier in Physics: the study of Magnetic systems using attosecond laser pulses. The main disciplines concerned are: Ultrafast laser sciences, Magnetism and Spin-Photonics, Relativistic Quantum Electrodynamics. Three issues of modern magnetism are addressed. 1. How fast can one modify and control the magnetization of a magnetic system ? 2. What is the role and essence of the coherent interaction between light and spins ? 3. How far spin-photonics can bring us to the real world of data acquisition and storage ? - We want first to provide solid ground experiments, unravelling the mechanisms involved in the demagnetization induced by laser pulses in a variety of magnetic materials (ferromagnetic nanostructures, aggregates and molecular magnets). We will explore the ultrafast magnetization dynamics of magnets using an attosecond laser source. - Second we want to explore how the photon field interacts with the spins. We will investigate the dynamical regime when the potential of the atoms is dressed by the Coulomb potential induced by the laser field. A strong support from the relativistic Quantum Electro-Dynamics is necessary towards that goal. - Third, even though our general approach is fundamental, we want to provide a benchmark of what is realistically possible in ultrafast spin-photonics, breaking the conventional thought that spin photonics is hard to implement at the application level. We will realize ultimate devices combining magneto-optical microscopy with the conventional magnetic recording. This new field will raise the interest of a number of competitive laboratories at the international level. Due to the overlapping disciplines the project also carries a large amount of educational impact both fundamental and applied.

2 492 561 €

Start date: 2010-05-01, End date: 2015-04-30

Knowledge of the state of the Earth mantle and its temporal evolution is fundamental to a variety of disciplines in Earth Sciences, from the internal dynamics to its many expressions in the geological record (postglacial rebound, sea level change, ore deposit, tectonics or geomagnetic reversals). Mantle convection theory is the centerpiece to unravel the present and past state of the mantle. For the past 40 years considerable efforts have been made to improve the quality of numerical models of mantle convection. However, they are still sparsely used to estimate the convective history of the solid Earth, in comparison to ocean or atmospheric models for weather and climate prediction. The main shortcoming is their inability to successfully produce Earth-like seafloor spreading and continental drift self-consistently. Recent convection models have begun to successfully predict these processes (Coltice et al., Science 336, 335-33, 2012). Such breakthrough opens the opportunity to combine high-level data assimilation methodologies and convection models together with advanced tectonic datasets to retrieve Earth's mantle history. The scope of this project is to produce a new generation of tectonic and convection reconstructions, which are key to improve our understanding and knowledge of the evolution of the solid Earth. The development of sustainable high performance numerical models will set new standards for geodynamic data assimilation. The outcome of the AUGURY project will be a new generation of models crucial to a wide variety of disciplines.

1 994 000 €

Start date: 2014-03-01, End date: 2020-02-29

Regulation of gene expression plays a key role in the ability of bacteria to rapidly adapt to changing environments and to colonize extremely diverse habitats. The relatively recent discovery of a plethora of small regulatory RNAs and the beginning of their characterization has unravelled new aspects of bacterial gene expression. First, the expression of many bacterial genes responds to a complex network of both transcriptional and post-transcriptional regulators. However, the properties of the resulting regulatory circuits on the dynamics of gene expression and in the bacterial adaptive response have been poorly addressed so far. In a first part of this project, we will tackle this question by characterizing the circuits that are formed between two widespread classes of bacterial regulators, the sRNAs and the two-component systems, which act at the post-transcriptional and the transcriptional level, respectively. The study of sRNAs also led to major breakthroughs regarding the basic mechanisms of gene expression. In particular, we recently showed that repressor sRNAs can target activating stem-loop structures located within the coding region of mRNAs that promote translation initiation, in striking contrast with the previously recognized inhibitory role of mRNA structures in translation. The second objective of this project is thus to draw an unprecedented map of non-canonical translation initiation events and their regulation by sRNAs. Overall, this project will greatly improve our understanding of how bacteria can so rapidly and successfully adapt to many different environments, and in the long term, provide clues towards the development of anti-bacterial strategies.

1 999 754 €

Start date: 2019-09-01, End date: 2024-08-31

The functioning of a single cell or organism is governed by the laws of chemistry and physics. The bridge from biology to chemistry and physics is provided by structural biology: to understand the functioning of a cell, it is necessary to know the atomic structure of macromolecular assemblies, which may contain hundreds of components. To characterise the structures of the increasingly large and often flexible complexes, high resolution structure determination (as was possible for example for the ribosome) will likely stay the exception, and multiple sources of structural data at multiple resolutions are employed. Integrating these data into one consistent picture poses particular difficulties, since data are much more sparse than in high resolution methods, and the data sets from heterogeneous sources are of highly different and unknown quality and may be mutually inconsistent, and that data are in general averaged over large ensembles and long times. Molecular modelling, a crucial element of any structure determination, plays an even more important role in these multi-scale and multi-technique approaches, not only to obtain structures from the data, but also to evaluate their reliability. This proposal is to develop a consistent framework for this highly complex data integration problem, principally based on Bayesian probability theory. Appropriate models for the major types data types used in hybrid approaches will be developed, as well as representations to include structural knowledge for the components of the complexes, at multiple scales. The new methods will be applied to a series of problems with increasing complexity, going from the determination of protein complexes with high resolution information, over low resolution structures based on protein-protein interaction data such as the nuclear pore, to the genome organisation in the nucleus.

2 130 212 €

Start date: 2012-05-01, End date: 2017-04-30

Diabetes has become one of the most widespread metabolic disorders with epidemic dimensions affecting almost 6% of the world’s population. Despite modern treatments, the life expectancy of patients with Type 1 diabetes remains reduced as compared to healthy subjects. There is therefore a need for alternative therapies. Towards this aim, using the mouse, we recently demonstrated that the in vivo forced expression of a single factor in pancreatic alpha-cells is sufficient to induce a continuous regeneration of alpha-cells and their subsequent conversion into beta-like cells, such converted cells being capable of reversing the consequences of chemically-induced diabetes in vivo (Collombat et al. Cell, 2009). The PI and his team therefore propose to further decipher the mechanisms involved in this alpha-cell-mediated beta-cell regeneration process and determine whether this approach may be applied to adult animals and whether it would efficiently reverse Type 1 diabetes. Furthermore, a major effort will be made to verify whether our findings could be translated to human. Specifically, we will use a tri-partite approach to address the following issues: (1) Can the in vivo alpha-cell-mediated beta-cell regeneration be induced in adults mice? What would be the genetic determinants involved? (2) Can alpha-cell-mediated beta-cell regeneration reverse diabetes in the NOD Type 1 diabetes mouse model? (3) Can adult human alpha-cells be converted into beta-like cells? Together, these ambitious objectives will most certainly allow us to gain new insight into the mechanisms defining the identity and the reprogramming capabilities of mouse and human endocrine cells and may thereby open new avenues for the treatment of diabetes. Similarly, the determination of the molecular triggers implicated in the beta-cell regeneration observed in our diabetic mice may lead to exciting new findings, including the identification of “drugable” targets of importance for human diabetic patients.

1 500 000 €

Start date: 2012-01-01, End date: 2016-12-31

Tissue morphogenesis is a complex process that emerges from spatially controlled patterns of cell shape changes. Dedicated genetic programmes regulate cell behaviours, exemplified in animals by the specification of apical constriction in invaginating epithelial tissues, or the orientation of cell intercalation during tissue extension. This genetic control is constrained by physical properties of cells that dictate how they can modify their shape. A major challenge is to understand how biochemical pathways control subcellular mechanics in epithelia, such as how forces are produced by interactions between actin filaments and myosin motors, and how these forces are transmitted at cell junctions. The major objective of our project is to investigate the fundamental principles of epithelial mechanics and to understand how intercellular signals and mechanical coupling between cells coordinate individual behaviours at the tissue level. We will study early Drosophila embryogenesis and combine quantitative cell biological studies of cell dynamics, biophysical characterization of cell mechanics and genetic control of cell signalling to answer the following questions: i) how are forces generated, in particular what underlies deformation and stabilization of cell shape by actomyosin networks, and pulsatile contractility; ii) how are forces transmitted at junctions, what are the feedback interactions between tension generation and transmission; iii) how are individual cell mechanics orchestrated at the tissue level to yield collective tissue morphogenesis? We expect to encapsulate the information-based, cell biological and physical descriptions of morphogenesis in a single, coherent framework. The project should impact more broadly on morphogenesis in other organisms and shed light on the mechanisms underlying robustness and plasticity in epithelia.

2 473 313 €

Start date: 2013-05-01, End date: 2018-04-30

"Transcriptional regulation of protein coding genes in eukaryotic cells requires a complex interplay of sequence-specific DNA-binding factors, co-activators, general transcription factors (GTFs), RNA polymerase II and the epigenetic status of target sequences. Nuclear transcription complexes function as large multiprotein assemblies and are often composed of functional modules. The regulated decision-making that exists in cells governing the assembly and the allocation of factors to different transcription complexes to regulate distinct gene expression pathways is not yet understood. To tackle this fundamental question, we will systematically analyse the regulated biogenesis of transcription complexes from their sites of translation in the cytoplasm, through their assembly intermediates and nuclear import, to their site of action in the nucleus. The project will have four main Aims to decipher the biogenesis of transcription complexes: I) Investigate their co-translation-driven assembly II) Determine their cytoplasmic intermediates and factors required for their assembly pathways III) Uncover their nuclear import IV) Understand at the single molecule level their nuclear assembly, dynamics and action at target genes To carry out these aims we propose a combination of multidisciplinary and cutting edge approaches, out of which some of them will be high-risk taking, while others will utilize methods routinely run by the group. The project builds on several complementary expertise and knowledge either already existing in the group or that will be implemented during the project. At the end of the proposed project we will obtain novel results extensively describing the different steps of the regulatory mechanisms that control the assembly and the consequent gene regulatory function of transcription complexes. Thus, we anticipate that the results of our research will have a major impact on the field and will lead to a new paradigm for contemporary metazoan transcription."

2 500 000 €

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

"Many physical models involve nonlinear dispersive problems, like wave or laser propagation, plasmas, ferromagnetism, etc. So far, the mathematical under- standing of these equations is rather poor. In particular, we know little about the detailed qualitative behavior of their solutions. Our point is that an apparent com- plexity hides universal properties of these models; investigating and uncovering such properties has started only recently. More than the equations themselves, these univer- sal properties are essential for physical modelisation. By considering several standard models such as the nonlinear Schrodinger, nonlinear wave, generalized KdV equations and related geometric problems, the goal of this pro- posal is to describe the generic global behavior of the solutions and the profiles which emerge either for large time or by concentration due to strong nonlinear effects, if pos- sible through a few relevant solutions (sometimes explicit solutions, like solitons). In order to do this, we have to elaborate different mathematical tools depending on the context and the specificity of the problems. Particular emphasis will be placed on - large time asymptotics for global solutions, decomposition of generic solutions into sums of decoupled solitons in non integrable situations, - description of critical phenomenon for blow up in the Hamiltonian situation, stable or generic behavior for blow up on critical dynamics, various relevant regularisations of the problem, - global existence for defocusing supercritical problems and blow up dynamics in the focusing cases. We believe that the PI and his team have the ability to tackle these problems at present. The proposal will open whole fields of investigation in Partial Differential Equations in the future, clarify and simplify our knowledge on the dynamical behavior of solutions of these problems and provide Physicists some new insight on these models."

2 079 798 €

Start date: 2012-04-01, End date: 2017-03-31