Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : NEDAG (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 1255697.5 €

New Directions in Derived Algebraic Geometry: In this proposal we propose to give a new impulsion on derived algebraic geometry by exploring new domains of applicability as well as developing new ideas and fundamental results. For this, we propose to focus on the, still very much unexplored, interactions of derived algebraic geometry with an extremely rich domain: singularity theory (to be understood in a broad sense, possibly in positive and mixed characteristics, but also singularities of meromorphic flat connections and of constructible sheaves). We plan to use the fruitful interactions between these two subjects in a two-fold manner: on the one hand derived techniques will be used in order to prove long standing open problems, and on the other hand we propose new developments in derived algebraic itself and thus open new research directions.The proposal has three major parts, interacting with each other in a coherent manner. In a first part we explore some direct applications of derived techniques to the study of singularities of degenerating families of proper schemes with the objective to prove a long standing major conjecture in the subject: the Bloch’s conductor formula. This is achieved by the introduction of a new trend of ideas in non-commutative geometry and more precisely by the introduction of a trace formula in the non-commutative setting. The second part is devoted to the exploration of trace and index formula for sheaves in two different, but very similar, setting: l-adic constructible sheaves and quasi-coherent sheaves with flat connections along a given algebraic foliations. In a third part we propose to make progress towards an unexplored domain: moduli spaces of flat, possibly irregular, connections on higher dimensional varieties and their relations with Poisson and symplectic geometry. The objective here is a far reaching generalization of fundamental results on moduli spaces of flat connections on open curves and their symplectic aspects.

Mots-clés : derived algebraic geometry,derived categories,non commutative geometry,trace and index formula,meromorphic connections,conductor formula,singularity theory
Projet ERC : ATLAS (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : University of Aveiro — Pays : Portugal — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2438987.5 €

New generations of devices for tissue engineering (TE) should rationalize better the physical and biochemical cues operating in tandem during native regeneration, in particular at the scale/organizational-level of the stem cell niche. The understanding and the deconstruction of these factors (e.g. multiple cell types exchanging both paracrine and direct signals, structural and chemical arrangement of the extra-cellular matrix, mechanical signals…) should be then incorporated into the design of truly biomimetic biomaterials. ATLAS proposes rather unique toolboxes combining smart biomaterials and cells for the ground-breaking advances of engineering fully time-self-regulated complex 2D and 3D devices, able to adjust the cascade of processes leading to faster high-quality new tissue formation with minimum pre-processing of cells. Versatile biomaterials based on marine-origin macromolecules will be used, namely in the supramolecular assembly of instructive multilayers as nanostratified building-blocks for engineer such structures. The backbone of these biopolymers will be equipped with a variety of (bio)chemical elements permitting: post-processing chemistry and micro-patterning, specific/non-specific cell attachment, and cell-controlled degradation. Aiming at being applied in bone TE, ATLAS will integrate cells from different units of tissue physiology, namely bone and hematopoietic basic elements and consider the interactions between the immune and skeletal systems. These ingredients will permit to architect innovative films with high-level dialogue control with cells, but in particular sophisticated quasi-closed 3D capsules able to compartmentalise such components in a “globe-like” organization, providing local and long-range order for in vitro microtissue development and function. Such hybrid devices could be used in more generalised front-edge applications, including as disease models for drug discovery or test new therapies in vitro.

Mots-clés : regenerative medicine,soft matter,bioinstructive materials
Projet ERC : ATLAS (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : University of Minho — Pays : Portugal — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 60000.0 €

New generations of devices for tissue engineering (TE) should rationalize better the physical and biochemical cues operating in tandem during native regeneration, in particular at the scale/organizational-level of the stem cell niche. The understanding and the deconstruction of these factors (e.g. multiple cell types exchanging both paracrine and direct signals, structural and chemical arrangement of the extra-cellular matrix, mechanical signals…) should be then incorporated into the design of truly biomimetic biomaterials. ATLAS proposes rather unique toolboxes combining smart biomaterials and cells for the ground-breaking advances of engineering fully time-self-regulated complex 2D and 3D devices, able to adjust the cascade of processes leading to faster high-quality new tissue formation with minimum pre-processing of cells. Versatile biomaterials based on marine-origin macromolecules will be used, namely in the supramolecular assembly of instructive multilayers as nanostratified building-blocks for engineer such structures. The backbone of these biopolymers will be equipped with a variety of (bio)chemical elements permitting: post-processing chemistry and micro-patterning, specific/non-specific cell attachment, and cell-controlled degradation. Aiming at being applied in bone TE, ATLAS will integrate cells from different units of tissue physiology, namely bone and hematopoietic basic elements and consider the interactions between the immune and skeletal systems. These ingredients will permit to architect innovative films with high-level dialogue control with cells, but in particular sophisticated quasi-closed 3D capsules able to compartmentalise such components in a “globe-like” organization, providing local and long-range order for in vitro microtissue development and function. Such hybrid devices could be used in more generalised front-edge applications, including as disease models for drug discovery or test new therapies in vitro.

Mots-clés : regenerative medicine,soft matter,bioinstructive materials
Projet ERC : MacroEntrepreneurs (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1202014.0 €

New micro-level data reveals enormous heterogeneity across firms in terms of their growth and survival. Young firms are the engines of aggregate job creation and productivity growth even though most startups fail or do not grow. Therefore, only a small share of high-growth firms generates the documented macroeconomic gains. Despite the aggregate importance, we know very little about why firm performance is so heterogeneous, whether these differences are predictable based on characteristics of business founders (entrepreneurs), and how choices of different entrepreneurs to start firms shape, and are shaped by, macroeconomic conditions. This research agenda studies the nexus of entrepreneurs, firms and the macroeconomy. First, I will estimate to what extent firm growth and survival are predictable from the time of entry and whether characteristics of business founders help explain such patterns. To do so, I will use detailed micro-level data from four countries and adopt a methodology not yet used in this context. Second, I will build a new macroeconomic model of firm dynamics in which business growth and survival profiles are shaped by heterogeneous entrepreneurs in accordance with the empirical evidence. While the link between heterogeneity of firms and their founders is absent in existing research, without it we cannot study current key policy questions. How does rising income and wealth inequality impact the macroeconomy by affecting choices to start new firms? How can policy promote the founding of high-growth firms, which are less plentiful in Europe compared to the U.S.? What general equilibrium feedback effects do such policies have on workers? The large degree of firm and founder heterogeneity makes both the empirical and theoretical parts of this agenda very challenging. At the same time, the importance of a better understanding of firm growth for further academic research and for economic policy makes this proposal particularly high-return.

Mots-clés : firm heterogeneity,dynamic stochastic general equilibrium models
Projet ERC : NextGen IO (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : CIC bioGUNE — Pays : Espagne — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1993575.0 €

NextGen_IO has a core focus on immuno-oncology, specifically on target discovery and drug development, to exploit several opportunities that the hypoxia pathway in T cells offers for the treatment of cancer. It is well recognised that the clinical response of immunotherapies depends on the ability of T-cells to mount an effective effector response, persist in treated patients and avoid exhaustion and toxicities. Several approaches to immunotherapy have shown promise in clinical trials, especially the use of immune checkpoint inhibitors and, more recently, autologous adoptive T-cell therapies. However, current state-of-the-art immunotherapies are only effective in a small fraction of patients, offering a medical need to be addressed in several cancer types. Importantly, the tumor microenvironment has specific features that impact the immune response, including decreased oxygenation, aberrant vascularization and altered nutrient availability; all these influence the success of immunotherapies. During the last 10 years, my research has been focused on elucidating the role of the oxygen sensing machinery in T cell function, and the link of hypoxia-driven metabolism and epigenetic modifications with T cell differentiation into effector and memory T cells within the context of cancer immunotherapy. The current proposal aims to exploit these previous findings with a multi-disciplinary strategy, to deliver several early-stage drug discovery outputs. The main objectives are: 1. Development of a novel small molecule inhibitor to modulate the hypoxic response in T cells. 2. Therapeutic target discovery in T cells, focused on hypoxia-driven epigenetic modifications. 3. Development of hypoxia-inducible molecular switches for adoptive T cell therapy. Successful completion of the project will allow me to further innovate and consolidate my position as a leader in this field, harness this pathway for therapeutic potential and explore potential combinatorial approaches.

Mots-clés : immunology,oncology,drug discovery,phage display,hypoxia,cell therapy,tumor microenvironment,small molecules,screening,t cells
Projet ERC : DISFILM (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : Université de Rennes — Pays : France — Rôle : PI
Acronyme de l'entité : UNIVRENNES
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1415506.0 €

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.

Mots-clés : bubbles,drops,foam,emulsion,liquid film stability,free interface flow,surfactant transport,energy absorption,complex fluid
Projet ERC : NSETHIO (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University Hospital Bonn — Pays : Allemagne — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 61000.0 €

Nodding syndrome (NS) is a neurological, incurable syndrome, currently affecting mainly children between 5 and 15 years of age in South Sudan, Uganda and Tanzania. Since 1950, when NS was first described, its cause has remained a mystery. NS is characterized by head-nodding (an atonic form of epilepsy), often followed by clonic - tonic seizures, developmental retardation and faltering growth. In the affected regions, NS is a major public health problem associated with severe socio-economic consequences. After exploratory missions to South Sudan, Uganda and the Democratic Republic of the Congo (DRC), we gathered epidemiological evidence that supports the hypothesis that NS is a disease caused by a pathogen transmitted by blackflies, the vectors that transmit the parasitic worm that causes onchocerciasis. This pathogen could be an unknown neurotropic virus or another pathogen that is transmitted either independently or as a symbiont of the worm. We postulate that this pathogen is able to cause typical NS, but also other forms of epidemic epilepsy. We hypothesise that the same disease is also endemic in other onchocerciasis hyper-endemic regions e.g. in the Mbam valley, Cameroon and the Orientale Province, DRC (where it is referred to as “river epilepsy”). In this project we aim to investigate our hypotheses in South Sudan, Uganda, Tanzania, Cameroon and the DRC with a trans-disciplinary approach including clinical-epidemiological, post-mortem, eco-entomological, and metagenomic studies. We will study the effect of vector control methods and ivermectin distribution on the incidence of river epilepsy. So far a multi-country study on NS was never done and nearly all previous studies were cross-sectional, carried out during short country visits. With this long term research plan we hope to finally discover the cause of NS and detect effective control strategies to decrease the incidence of epilepsy in onchocerciasis endemic areas.

Mots-clés : vector born diseases,onchocerciasis
Projet ERC : NOISE (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Hungarian Academy of Sciences — Pays : Hongrie — Rôle : PI
Acronyme de l'entité : MTA
Type d'entité : Recherche
Financement ERC de l'entité : 1386363.52 €

Noise-sensitivity of a Boolean function with iid random input bits means that resampling a tiny proportion of the input makes the output unpredictable. This notion arises naturally in computer science, but perhaps the most striking example comes from statistical physics, in large part due to the PI: the macroscopic geometry of planar percolation is very sensitive to noise. This can be recast in terms of Fourier analysis on the hypercube: a function is noise sensitive iff most of its Fourier weight is on "high energy" eigenfunctions of the random walk operator. We propose to use noise sensitivity ideas in three main directions: (A) Address some outstanding questions in the classical case of iid inputs: universality in critical planar percolation; the Friedgut-Kalai conjecture on Fourier Entropy vs Influence; noise in First Passage Percolation. (B) In statistical physics, a key example is the critical planar FK-Ising model, with noise being Glauber dynamics. One task is to prove noise sensitivity of the macroscopic structure. A key obstacle is that hypercontractivity of the critical dynamics is not known. (C) Babai’s conjecture says that random walk on any finite simple group, with any generating set, mixes in time poly-logarithmic in the volume. Two key open cases are the alternating groups and the linear groups SL(n,F2). We will approach these questions by first proving fast mixing for certain macroscopic structures. For permutation groups, this is the cycle structure, and it is related to a conjecture of Tóth on the interchange process, motivated by a phase transition question in quantum mechanics. We will apply ideas of statistical physics to group theory in other novel ways: using near-critical FK-percolation models to prove a conjecture of Gaboriau connecting the first ell2-Betti number of a group to its cost, and using random walk in random environment to prove the amenability of the interval exchange transformation group, refuting a conjecture of Katok.

Mots-clés : noise sensitivity,discrete fourier analysis,critical percolation,ising and fk p,q  models,scaling limits,mixing time of random walks,hypercontractivity,amenability,cost,permutation groups
Projet ERC : CYPNASH (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : University of Edinburgh — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Non-alcoholic steatohepatitis (NASH) is an increasingly prevalent chronic liver disease (3-4% of the US population) for which there is currently no approved drug therapy. In the absence of innovative treatments healthcare costs associated with this disease are set to triple over the next decade. To address this unmet medical need, the pharmaceutical industry is currently pursuing a range of liver fibrosis drug discovery programs based on different mode of actions. A compelling mechanism for treating liver damage is pharmacological modulation of the mitochondrial permeability transition pore in liver cells via inhibition of the protein cyclophilin D. However existing cyclophilin inhibitors based on peptidic macrocyclic scaffolds are challenging to optimize into sub-type selective orally bioavailable agents suitable for clinical trials of liver fibrosis. As part of basic research activities undertaken during ERC StG EBDD to validate a computational-biophysical drug discovery platform, we have discovered a structurally novel family of small molecules that inhibit cyclophilins by targeting a previously unexplored binding pocket. The objective of this POC is to identify a lead compound in this family with potential for development towards a NASH clinical candidate. Such a candidate will form the basis of follow-on lead optimisation programs pursued via partnering or out-licensing with a pharmaceutical partner. The activities of this POC will focus on assembling a data package of in vitro DMPK, in vivo PK, in vitro sub-type selectivity and in vitro and in vivo efficacy measurements in relevant cellular and animal models of liver fibrosis. This POC has been designed in consultation with a major pharmaceutical company and assembles a team of physical and biological scientists and business development executives to maximize the likelihood of delivering a valuable preclinical NASH asset.

Mots-clés : drug discovery,medicinal chemistry,liver fibrosis,cyclophilin
Projet ERC : LEGALARCHITECTURES (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
Entité participante : National University of Ireland — Pays : Irlande — Rôle : PI
Acronyme de l'entité : NUI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1494650.0 €

Non-compliance with the EU’s environmental rules is one of the key weaknesses of the EU’s environmental policy. This research investigates the influence that environmental governance laws have on compliance decisions, and how we might best design our laws to maximise compliance. One of the most important trends in European environmental regulatory techniques over the past decade has been the shift from hierarchical, state-led government via command-and-control techniques, to decentralised, society-led governance by local private actors (see, e.g., Jordan et al (2013)). The EU has strongly supported efforts to empower compliance and enforcement by non-State actors, as embodied in the UNECE Aarhus Convention and implementing laws. Yet little is known about how this major change in environmental governance laws has actually influenced compliance levels in practice, and why. Can the design of environmental governance rules influence us not only to comply with the letter of the law, but also to go further? This research seeks to fill that gap by means of an interdisciplinary, bottom-up study of the relationships between the legal architecture of environmental governance and compliance decisions, in a selected field of EU environmental policy (biodiversity), and in three selected States. It is novel in terms of theory, because it tests new hypotheses about the effects environmental governance rules have on compliance. It is novel in terms of methodology, because in testing these hypotheses, it uses techniques that have not up to now been applied to measure the effect of law. It is challenging, because it sits at the intersection between the law and economics, socio-legal and governance/regulatory literatures, and brings together multiple methods from these fields to test its hypotheses. It has potentially high impact, because non-compliance is one of the most serious problems the EU’s environmental policy faces, and is closely linked to environmental outcomes.