Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : Controlling MAC (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Imperial College London — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999990.0 €

Structural basis of controlling the membrane attack complex Complement is a fundamental component of the human immune system; central to the battle between hosts and pathogens. The membrane attack complex (MAC) is the direct killing arm of complement that acts by forming large pores in target cell membranes. Uncontrolled activation results in by-stander damage, which can have devastating consequences for host cells and impact inflammatory pathologies, thrombosis and cancer. Understanding how MAC activity is controlled on human cells during an immune response is a major unresolved question. My lab has pioneered the use of cryo electron microscopy (cryoEM) to investigate the molecular mechanism underpinning MAC assembly. We have defined the stoichiometry of the complex and identified interaction interfaces that determine its sequential assembly mechanism. Recent data from my lab has now revealed atomic resolution information for the complete transmembrane pore. Results from my lab have provided a molecular and biophysical basis for MAC pore formation, which has led to a general mechanism for how proteins cross lipid bilayers. Here, the goal is to understand the structural basis for how MAC activity is controlled by (i) cell surface receptor CD59, (ii) removal of pores from the plasma membrane, and (iii) clearance of assembly by-products from the plasma. MAC interacts with a defined set of cellular proteins through these three pathways. In this proposal, we will integrate structural information that spans cellular to molecular length scales. Recent technical advances in cryoEM, cryo soft X-ray tomography (cryoSXT) and correlated fluorescence imaging make it now possible to address how MAC activity is controlled in and around the plasma membrane. In doing so, we will answer a longstanding question in immunology and open new research directions exploring fundamental cellular processes. These results will provide a foundation for the development of novel therapeutics.

Mots-clés : pore forming proteins,complement
Projet ERC : HT-S4DefOx (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
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 : 2493277.0 €

Structural materials exposed at high temperatures (650°C-1200°C) and severe loads are prone to both local oxidation-assisted deformation and deformation-assisted surface reactivity. Material evolutions within the sub-surface region affected by oxidation (0.1 to 100 µm deep gradient) generally drive premature damage and the unexpected ruin of bulky structural components. Therefore, assessing the evolutions of the local deformation at the sub-grain scale at high temperature using micro- and mesomechanical approaches is the key point to clarify thermo-mechano-chemical interactions favouring early damage. HT-S4DefOx aims to tackle such small-scale and pluridisciplinary investigations on Ni-based and Ti-based model materials. Advanced high temperature micromechanical techniques (high resolution-digital image correlation (HR-DIC), in-situ TEM mechanical testing, in-situ micropillar/nanoindentation testing, synchrotron nano-tomography and topotomography) will be purposely coupled with numerical simulations (phase field-coupled crystal plasticity finite element methods). My unique expertise in mesoscale ultrathin specimen preparation and testing allows the present experimental investigation of the coupling between surface reactivity and local deformations. The development of novel mesoscale flexural techniques with real-time 3D observation of the specimen deformation up to 1000°C will finally bridge the gap between micro- and macroscale mechanical characterisations, with an emphasis on graded properties materials. Investigating sub-surface behaviour during oxidation lies in the inability to achieve robust measurement at such hidden location. In addition, the surface texture evolution while oxide growth constitutes another significant obstacle. Therefore, smart surface monitoring for high temperature HR-DIC at the microscale and inverse numerical methods will give unique and quantitative information on the local mechanical behaviour of such “invisible” materials.

Mots-clés : high temperature oxidation,mechanics of material
Projet ERC : NPSkills (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : University of Bonn — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1050161.0 €

Structural models are key tools of economists to evaluate and design policies. These models specify economic environments, estimate mechanisms that determine outcomes, and can be used for counterfactual predictions. One important class of models deals with skill and human capital formation, which is an important driver of economic growth and inequality. These models study the determinants of skill formation and the timing of optimal investments in children. Since structural models require simplifying assumptions, they are also prone to misspecification. The proposed research shows that existing skill formation models rely on seemingly innocuous normalizations, which can severely impact counterfactual predictions. For example, simply changing the units of measurements of observed variables can yield ineffective investment strategies and misleading policy recommendations. I plan to tackle these problems by providing a new comprehensive identification analysis and by focusing on a novel set of important policy-relevant parameters that yield robust conclusions. These issues and solutions might extend to many other structural models with latent variables. In addition, I will provide a new flexible estimator for the policy-relevant features and analyze various data sets to reevaluate policy recommendations with potentially large impacts on costs and benefits of large public investments in children, economic growth, and inequality. Estimation will rely on other objectives of this proposal, which aim to develop new econometric tools. These tools are important contributions on their own rights and are applicable in a wide range of settings. They allow researchers to obtain more precise nonparametric estimators and more reliable conclusions by using shape restrictions implied by economic theory and data-driven dimension reduction techniques. By also providing guidance on which estimation method to use in practice, these results can have a large impact on empirical research.

Mots-clés : structural models,skill formation,misspecification,normalizations,counterfactual implications,nonparametric methods,shape restrictions,dimension reduction
Projet ERC : GeoSub (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Scuola Internazionale Superiore di Studi Avanzati — Pays : Italie — Rôle : PI
Acronyme de l'entité : SISSA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1171465.0 €

Sub-Riemannian spaces are geometrical structures that model constrained systems, and constitute a vast generalization of Riemannian geometry. They arise in control theory, harmonic and complex analysis, subelliptic PDEs, geometric measure theory, calculus of variations, optimal transport, and potential analysis. In the last 10 years, a surge of interest in the study of geometric and functional inequalities on sub-Riemannian spaces revealed unexpected behaviours and intriguing phenomena that failed to fit into the classical schemes inspired by Riemannian geometry. In this project, I aim to develop a framework of geometric and functional interpolation inequalities adapted to sub-Riemannian manifolds, and to use this theory to tackle old and new problems concerning the geometric analysis of these structures. The project focuses on the following interconnected topics: (i) the development of a unifying theory of curvature bounds including sub-Riemannian structures, (ii) the study of measure contraction properties of Carnot groups, (iii) applications to isoperimetric-type problems, and (iv) applications to the regularity of the sub-Riemannian heat kernel at the cut locus. The project adopts a unique approach combining methods from geometric control theory, optimal transport and comparison geometry that I developed in recent years, and which already allowed me and my collaborators to obtain important results in the field. The project aims to achieve an ambitious unification program, solve long-standing problems, and explore new research directions in sub-Riemannian geometry, with an impact in several neighbouring areas, including geometric analysis on non-smooth spaces, analysis of hypoelliptic operators, geometric measure theory, spectral geometry. My long-term purpose is to build a leading research group in sub-Riemannian geometry, to significantly advance our understanding of Geometry under non-holonomic constraints.

Mots-clés : sub riemannian geometry,carnot carath odory spaces,ricci curvature bounds,isoperimetric problems,carnot groups,optimal transport
Projet ERC : TRUE DEPTHS (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : University of Pavia — Pays : Italie — Rôle : PI
Acronyme de l'entité : UNIPV
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1697500.0 €

Subduction of one tectonic plate below another is the primary cause of catastrophic geological events such as earthquakes and explosive volcanism that directly impact thousands of kilometers of coastal and mountain areas located on convergent margins. Real-time geophysical or seismic data only provide static snapshots of these subduction zones today. Therefore, quantitative understanding of the rates and true depths of subduction can only be achieved by determining the pressure-temperature-time-depth histories of Ultra-High-Pressure Metamorphic (UHPM) rocks that have been subducted to pressures greater than 3 GPa and subsequently exhumed. Conventional mineral thermo-barometry is severely challenged in UHPM terraines and thus the mechanisms attending the downwards transport of crustal material, and its return back to the Earth’s surface (exhumation), are still a matter of vigorous debate. The TRUE DEPTHS project will develop X-ray diffraction analysis of the anisotropic elastic interactions of inclusion minerals trapped inside host minerals. I will develop non-linear elasticity theory to provide a method that will be uniquely able to determine whether significant deviatoric stresses are recorded by UHPM rocks. By applying this method to samples from carefully selected field areas, I will be able to determine if metamorphic phase equilibria represent the true depths of UHPM, in which case subduction to depths in excess of 90 km must occur. Alternatively, quantitative measurements of large deviatoric stresses could indicate that tectonic over-pressure can account for the observed phase equilibria, thus not requiring deep subduction. If overpressurized domains are present in tectonically thickened lithosphere, they may represent a driving force for stress release leading to earthquakes. The results will provide new constraints on earthquake triggering mechanisms and how the styles of subduction and its detailed mechanisms have evolved over Earth’s history.

Mots-clés : elasticity,mineralogy,ultra high pressure metamorphic rocks,deep subduction
Projet ERC : BayesianMarkets (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : Erasmus University Rotterdam — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : EUR
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Subjective data play an increasing role in modern economics. For instance, new welfare measurements are based on people’s subjective assessments of their happiness or their life satisfaction. A problem of such measurements is that people have no incentives to tell the truth. To solve this problem and make those measurements incentive compatible, I will introduce a new market institution, called Bayesian markets. Imagine we ask people whether they are happy with their life. On Bayesian markets, they will trade an asset whose value is the proportion of people answering Yes. Only those answering Yes will have the right to buy the asset and those answering No the right to sell it. Bayesian updating implies that “Yes” agents predict a higher value of the asset than “No” agents do and, consequently, “Yes” agents want to buy it while “No” agents want to sell it. I will show that truth-telling is then the optimal strategy. Bayesian markets reward truth-telling the same way as prediction markets (betting markets) reward people for reporting their true subjective probabilities about observable events. Yet, unlike prediction markets, they do not require events to be objectively observable. Bayesian markets apply to any type of unverifiable truths, from one’s own happiness to beliefs about events that will never be observed. The present research program will first establish the theoretical foundations of Bayesian markets. It will then develop the proper methodology to implement them. Finally, it will disseminate the use of Bayesian markets via applications. The first application will demonstrate how degrees of expertise can be measured and will apply it to risks related to climate change and nuclear power plants. It will contribute to the political debate by shedding new light on what true experts think about these risks. The second application will provide the first incentivized measures of life satisfaction and happiness.

Mots-clés : expectations,subjective data,belief elicitation,subjective probabilities,prediction markets,scoring rules,bayesian truth serum,market design,experts
Projet ERC : BRAVIUS (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : Partner
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 373490.0 €

Subjectivity defines the subject who is perceiving, feeling, thinking, acting, and is essential to understand the conscious mind from the inside. However, subjectivity, or non-reflective first-person perspective, is not identified as a core concept in cognitive neuroscience and its neural basis remain largely unknown. BRAVIUS offers a unified framework to appraise both the concept and the neural mechanisms generating subjectivity. The hypothesis relies on two vital organs that generate their own rhythmic electrical activity, the stomach and the heart, and therefore constantly send information up to the neocortex, even in the absence of bodily change. Cortical responses to those visceral organs would define the organism as an entity at the neural level, and create a subject-centered referential from which first-person perspective can develop. In other words, the cardiac and gastric pacemakers could feed the brain with self-specifying inputs. BRAVIUS builds on previous theories and studies on visceral states but focuses on ascending information, from viscera to brain, and does not require visceral states to change nor to be consciously perceived. Experimentally, BRAVIUS measures the understudied neural response evoked by heartbeats and introduces a new measure, the electrogastrogram, to quantify the slow gastric pacemaker. BRAVIUS will test with magneto-encephalography (MEG) the role of neural responses to ascending visceral signals in generating subjectivity by cutting across domains of cognitive sciences and exploring diverse paradigms where subjectivity is engaged: perceptual consciousness, self-consciousness, emotions and decision making. BRAVIUS will further explore how cardiac and gastric ascending signals shape the temporal (MEG) and spatial (fMRI) organization of spontaneous brain activity. The project outcome is a detailed mechanistic neural account of the most private part of the human mind, and a unified concept of subjectivity across cognitive domains.

Mots-clés : consciousness,brain body interactions,spontaneous brain activity,magneto encephalography
Projet ERC : ImmunoCode (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Eindhoven University of Technology — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : TU/e
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1812143.0 €

Successful immunotherapy against cancer is the result of a multitude of cellular interactions within the immune system. It is highly exciting how vaccination with small numbers of human plasmacytoid dendritic cells (pDCs) can induce anti-tumour immunity in metastatic cancer patients. Remarkably, how pDCs, as an extremely rare subset of cells, can act as Swiss army knives to regulate the tight balance between tolerance and immunity: i.e. secrete massive amounts of type I IFNs, prime T cells and exert cytotoxic effector functions, is still elusive. Do pDCs possess all functions or comprises the population distinct functional subsets all with their specialized roles. I will unravel which pDC is superior in inducing cytotoxic T cells (CTLs) for augmented cancer immunity. Despite advances in single cell technologies, understanding the role of heterogeneity in immune cell populations, remains poorly understood. In ImmunoCode, I will develop a novel and ambitious single cell technology platform, wherein innovative microfluidic approaches and single cell transcriptomics allow 1) functional analysis of single (pairs of) immune cells and 2) design of minimal environments under the omission of external factors that could influence cellular behaviour. This approach will provide me with the unique opportunity to unravel pDC function and plasticity. Although in this ERC proposal I will focus on understanding pDCs heterogeneity, my technology can in fact be exploited to any cell type that shows heterogeneous function. My unique and high-risk technical approach allows for decoding immune cell-cell or cell-pathogen interactions longitudinally and in great detail which will revolutionise the fields of immunology and cellular immunotherapy. Ultimately, ImmunoCode will have a tremendous impact by refining the design of vaccine strategies and the development of differently composed cellular vaccines to battle cancer and infectious and auto-immune diseases.
Projet ERC : SUMMIT (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Spanish National Research Council — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 2499187.0 €

Sulphur is an essential element for life that cycles rapidly in the pelagic ocean in the form of biogenic dimethylated compounds. Over three decades, dimethylated sulphur has been intensively investigated for its emission to the atmosphere and its suggested roles in returning sulphur to continents and in climate regulation. While the climate connection still awaits definitive confirmation or denial, these research efforts have provided important advances in plankton physiology and ecology, since these forms of sulphur arise from organism adaptation to saline and sunlit waters and are integral to the food web machinery. Previous studies have disclosed biochemical and trophic cycling pathways and their taxonomic affiliations. Also, evidence for their behaviour as infochemicals in organism-organism communication has been obtained. However, their contribution to the functioning of marine ecosystems remains largely unexplored, particularly with respect to the emerging renewed picture of food webs, where classical functional roles blur and concepts like multifunctional organisms and interdependence become the rule rather than the exception. I propose to bridge microbial physiology, ecology and biogeochemistry to explore new roles of dimethylated sulphur in microbial food-web interactions. I will build upon a combination of molecular tools, isotopes, single-cell analyses, physiological dyes, chemotaxis experiments, modelling, sea-going opportunities and an existing collection of samples from diverse oceanic biomes. Hypothesis-driven research is expected to yield paradigm shifts in (i) phytoplankton-bacteria interactions through nitrogen fixation and vitamin exchange; (ii) phytoplankton-phytoplankton interactions to overcome energy limitation to growth; (iii) phytoplankton-herbivore interactions for selective grazing on weakened prey. Overall, I intend to assess if interactions through dimethylated sulphur make microbial food-webs more robust and efficient.

Mots-clés : dimethylated organic sulphur,plankton,picoalgae,bacteria,microzooplankton,nitrogen fixation,dmsp,vitamin b12,methionine,chemotaxis,mutualism,food web
Projet ERC : Nanostress (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Amsterdam — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UvA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Summary: I will exploit novel molecules whose fluorescence properties depend strongly on the environment, notably on their spatial confinement, to study local stresses in complex materials down to the nanometer length scale and with unprecedented temporal resolution. Based on successful preliminary tests, I will develop this innovative methodology to tackle the fundamental scientific challenge of quantifying the long-range and very non-linear elasto-plastic stresses that govern the dynamics of friction, the glass transition and rheology. Friction is an immense global source of energy loss; the glass transition is perhaps the most important unsolved problem in condensed matter physics; and rheology in complex fluids is at the same time ubiquitous and poorly understood. The common denominator of these three open challenges is that in each, the material’s macroscopic mechanical behavior results from a complex interplay between microscopic stresses that remain ill characterized. This presents a scientific bottleneck as well as a major obstacle in the engineering of many important materials and tools such as ball bearings, plastics and foodstuffs. The fluorescent environmentally sensitive probes will allow me to achieve breakthrough results in three areas at once: (1) Locally measuring stresses in a frictional contact; (2) Probing the glass transition by local stress and viscosity measurements; (3) Visualizing and quantifying stress transmission in flowing complex fluids to explain non-Newtonian and non-local viscosity effects microscopically. I have a track record in providing new insights in long-standing problems, spurring renewed scientific interest, and in combining fundamental research with potential for technological innovation. By probing local stresses in much more detail than was possible before, this project will break open some of the toughest research areas in non-linear physics and (statistical) mechanics with far-reaching engineering consequences.

Mots-clés : friction,glass transition,yield stress materials