Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : ElectroFun (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Göttingen — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : GAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499423.75 €

The impressive progress in organic chemistry during the past century has propelled this discipline to its current central position as the enabling technology in the physical and life sciences. Despite remarkable advances, our ability to assemble molecules of even moderate structural complexity remains unsatisfactory, since these syntheses continue to be inefficient, rely on a high number of reaction and purification steps, and generate undesired, often toxic waste. These features led to the general consensus on the need for greener chemical transformations that will stimulate the transition to more sustainable chemical industries. Conventional strategies in molecular syntheses make use of chemical redox reagents and directing groups, the installation of which results in costly reaction steps. Therefore, an environmentally-sound alternative is represented by molecular electrosynthesis to enable direct electro-functionalization of inert bonds. This strategy avoids prefunctionalizations, and prevents undesired waste formation, overall enabling a streamlining of organic synthesis for late-stage diversification. While significant recent progress has been achieved in electrosynthesis, available methods are limited, and key challenges remain, particularly metalla-electrocatalyzed transformations beyond the realm of innate reactivity are in high demand. I aim at addressing these major obstacles of selective electrochemical functionalizations. Thus, I will devise efficient electrochemical C–H and CO2 functionalizations without directing groups, gain full selectivity control in molecular electrocatalysis, and achieve late-stage polymer and peptide diversifications. Establishing a comprehensive set of sustainable strategies for organic electrocatalysis, including paired electrolysis, hybrid catalysts and electrophotocatalysis, will undeniably have a tremendous impact on applied areas, such as medicinal chemistry, drug discovery, chemical industries and material sciences.

Mots-clés : organic electrosynthesis,c h activation,metal catalysis,electrocatalysis,electrophotocatalysis,paired electrolysis,late stage diversification
Projet ERC : ENVIROIMMUNE (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Vlaams Instituut voor Biotechnologie — Pays : Belgique — Rôle : PI
Acronyme de l'entité : VIB
Type d'entité : Recherche
Financement ERC de l'entité : 1499041.0 €

The incidence of autoimmune diseases in developed societies is increasing at high rates, but the underlying cause for this phenomenon has not been elucidated yet. Since the genetic architect remains considerably stable, this increase is likely associated with changes in the environment. Autoimmunity is linked to an imbalance of pro-inflammatory Th17 cells and anti-inflammatory Foxp3+ regulatory T cells (Treg). However, little is known regarding environmental factors that influence the Th17/Treg balance. We recently discovered that a sodium-rich diet severely exacerbates experimental autoimmune encephalomyelitis (EAE) through an increased induction of pathogenic Th17 cells. Surprisingly, our preliminary data indicate that high-salt conditions also significantly impair Treg function, resembling a phenotype observed in several human autoimmune diseases. In addition, we have evidence that a high-salt diet affects the gut microbiota, implicating possible indirect effects on immune cells in vivo. Based on these findings we hypothesize that excess dietary salt represents an environmental risk factor for autoimmune diseases by modulating the Th17/Treg balance by several direct and indirect mechanisms. To address this hypothesis we will 1) examine the underlying mechanisms of high-salt induced Treg dysfunction and effects on the Treg/Th17 balance by molecular and functional analysis in vitro and compare it to known risk variants of human autoimmune diseases, and 2) define direct and indirect effects of excess dietary salt on the Th17/Treg balance and autoimmunity in vivo and explore potential novel pathways for targeted interventions. Thus, the proposed study will uncover the impact of a newly discovered environmental modulator of the immune cell balance and will ultimately pave the way for new approaches in therapy and prevention of autoimmune diseases.

Mots-clés : autoimmunity
Projet ERC : SENF (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Bristol — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1553043.0 €

The incorporation of fluorine into organic compounds is extremely important for designing molecules with specific function. Fluorine is primed for improving the pharmacokinetic properties of drugs and agrochemicals, and is crucial for the life-changing imaging technique, Positron Emission Tomography (PET). Thus, selective fluorination is an area of significant interest in organic synthesis. This research programme will develop a concept that promises to revolutionise fluorination chemistry. While nucleophilic fluoride (F-) sources are inexpensive and readily available, they have unfavourable reactivity compared to electrophilic fluorine sources (F+), which are typically expensive, wasteful and not suited to either large scale synthesis or PET. By transmuting F- into F+, we can get the best of both worlds! We will develop a concept based on umpolung (polarity reversal) to invent a number of novel synthetic methodologies or to expand useful reactions into new chemical space. The overall vision is to create new pathways to new bioactive molecules that are either more potent, have improved pharmacokinetics, or can be new radiochemical tracers. Our strategy relies on the combination of catalysis and electrochemical oxidation to perform this thermodynamically demanding task. The use of electrochemistry is essential for this strategy, because it is necessary to be able to ‘dial-in’ any oxidising potential with high control. New organo- and organometallic catalysts, heterogeneous electrocatalysts and fluoride sources will be developed as part of the studies, which will be of value to the fields of fluorination, homogeneous catalysis, synthesis and energy research. Medicinal, process and radio chemists will all benefit as their toolbox of methods will expand, thereby facilitating the discovery and manufacture of drugs and chemicals that improve the quality of human life around the globe.

Mots-clés : organic electrochemistry,electrocatalysis,fluorination,organometallics,heterogeneous catalysis
Projet ERC : PREDICT-CARE (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : University of Parma — Pays : Italie — Rôle : PI
Acronyme de l'entité : UNIPR
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2309518.0 €

The increased burden of cardiometabolic diseases is a major societal challenge worldwide. Plant-based diets, rich in bioactive compounds such as (poly)phenols, may promote cardiometabolic health. However, the preventive effects of these bioactives depend on the individual capacity to produce, and respond to, (poly)phenol metabolites. This heterogeneity in the individual response to the consumption of (poly)phenols is the main hindrance to exploit their potential for the prevention of cardiometabolic diseases through effective dietary strategies. I aim to implement integrative tools for the prediction, at individual level, of the cardiometabolic response to the consumption of dietary (poly)phenols, taking into account inter-individual differences in both metabolism and health effects of these plant food bioactives. My vision is understanding the determinants leading to individual variability in the production of phenolic metabolites and driving cardiometabolic responsiveness to (poly)phenol consumption. I will be identifying comprehensive metabolic phenotypes (metabotypes) for main dietary (poly)phenols and the factors associated with their formation. Then, I will demonstrate the association between phenolic metabotypes and cardiometabolic health. Last, I will develop an integrative, high-throughput platform to identify phenolic metabotypes and to predict cardiometabolic responses to the consumption of dietary (poly)phenols considering individual’s makeup. PREDICT-CARE will develop new concepts, new methodologies and a new analytical platform. It relies on the integration of factors determining inter-individual variability, the deployment of translatable nutrition interventions, and the application of predictive modelling. PREDICT-CARE will lead to long-lasting breakthroughs and will build a new scenario in preventive, evidence-based, personalised nutrition strategies with these major dietary plant bioactives.

Mots-clés : polyphenol,phenolic metabolite,metabotype,inter individual variability,plant bioactive,personalised nutrition,bioavailability,cardiometabolic health,nutritional intervention
Projet ERC : IMMUNOBIOME (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2304375.0 €

The inflammatory bowel diseases (IBD) Crohn’s disease and ulcerative colitis manifest at the host-microbiota interface. The recently revealed genetic underpinning of IBD points towards an aberrant immune response to the intestinal microbiota. The prediction of genetically-impaired microbial handling is exemplified by key risk genes overlapping between leprosy, an infectious disease, and Crohn’s disease. A vigorous search for microbial triggers of IBD, which could also help explain the rising incidence and prevalence of this debilitating condition throughout the world, via high-throughput sequencing studies have indeed revealed structural alterations of the microbiota (‘dysbiosis’) compared to healthy individuals, although it is methodologically impossible to resolve cause-effect relationships of these associations. Here we propose a two-tier strategy to overcome these limitations of current methods to uncover the microbial targets of the ‘inappropriate’ immune response that characterises IBD. The first tier is based on an entirely novel, and potentially disruptive, method (termed MiIP-Seq - Microbial Immunoprecipitation and Sequencing) that we have developed. MiIP-Seq allows directed metagenomic sequencing of microbes complexed with immunoglobulins in patients with IBD, and hence the identification of those microbes within the microbiota that are targeted by the pathological IgG immune response; induction of massive mucosal IgG exceeding IgA that prevails in health is a core characteristic of IBD. The second tier builds on transfer of the microbiota from patients with active IBD harbouring dominant IBD risk genes into mice genetically hypomorphic at the orthologues of these risk genes, and to resolve the hierarchy of immunologically targeted microbes within the humanised microbiota via MiIP-Seq. Hence, via exploiting the lens of the immune system and harnessing genetic insight, this study will unravel the ‘environmental, microbial’ triggers and perpetuators of IBD.

Mots-clés : aetiology,inflammatory bowel disease,host,microbe mutualism
Projet ERC : ImAgine (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1489520.0 €

The innate immune system has evolved signalling receptors, which detect various stresses including microbial infection but also signals emanating from non-infectious cellular damage. Upon activation, these signalling receptors can trigger a variety of distinct effector responses collectively aimed towards maintaining the integrity of the host. The recognition of cytosolic DNA through the cGAS-STING pathway is a fundamental mechanism through which pathogens and cellular stress evoke an inflammatory response. Recently, we discovered a new role of the cGAS-STING pathway in promoting cellular senescence, a critical stress response program that is emerging as a key driver of aging. On the basis of this finding, the overarching gaol of ImAgine is to further explore the molecular links that exist between the mechanisms of innate immune signalling and those underlying aging processes. Specifically, we will address whether the cGAS-STING pathway acts as a contributor to age-associated phenotypes and we will interrogate mitotic perturbations as a physiological source of age-associated damage that activates the innate DNA sensing machinery. Another intriguing possibility emerging from our work is that cellular senescence is relevant for the host response against pathogens. Utilising an array of genetic and pharmacological tools, we will challenge this idea and molecularly decipher the role of senescent cells in physiological models of acute and chronic infection. A detailed picture of the interplay between innate immune pathways and cellular ageing will not only be a critical step towards a global understanding of fundamental host response mechanisms, but may also provide new concepts for the treatment of diseases that are associated with infectious diseases or ageing.
Projet ERC : MULTILAT (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499869.99 €

The integration of materials and architectural features at multiple scales into structural mechanics changed the way buildings were designed and gave us the Eiffel Tower, for example. This approach led to the development of computational design approaches used in modern day construction and it is believed that similar principles can be applied to the design and manufacture of new lattice-based microstructures. This vision, of fundamentally changing how materials are developed, is the inspiration behind this programme. A systematic procedure for generating multi-phase lattice materials - MULTILAT - will be developed by micro-architectural design, in order to fill gaps in material property space. New engineering devices and products frequently require materials with extreme properties, such as high strength and toughness at low density, and a systematic means of material invention is needed. This proposal breaks much ground in developing new fundamental concepts, ranging from micro-architectured surface coatings to inter-penetrating bulk lattices of dissimilar materials. Based on Fleck’s earlier work on the mechanics of foams and lattice materials, the unique and novel aspects of the proposed research are to design multi-phase lattice materials made from a wide range of materials, topologies and length scales. The focus will be on 2 inter-penetrating lattices, but the topology of each can range from 1D fibres, through 2D meshes to 3D lattices and foams. A focus will be lightweight strong and tough lattices, and surface lattices (as coatings). Examples from Nature will be used to develop fundamental concepts, ranging from the high toughness and ductility of the root of a tree branch, to the high toughness of human skin and underlying fat. The successful project will lay scientific foundations for new engineering devices and solutions that will improve our competitiveness and quality of life.

Mots-clés : solid mechanics,multi functional materials
Projet ERC : lightMaterInt (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer science and informatics
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 0.0 €

The interaction between light and material leads to beautiful visual phenomena that greatly enrich our perception of the world. The ability to measure and model light scattering is central to almost any field of science. However, light transport in rich scenes is a complex process involving a long sequence of scattering events. Computationally modeling, reproducing and acquiring the processes generated so easily by Mother Nature is an extremely challenging task. While several computational models have been proposed, they are all making various simplifying assumptions that cannot capture the full complexity of light transport processes in nature. In the proposed research, we suggest new measurement strategies and new inference algorithms that will allow us to infer more information on light and material interaction. Specifically, the research will focus on the following tasks: (i) Acquiring internal sub-scattering, and recovering the volumetric structure of partially translucent objects using transient imaging data; (ii) Acquiring external illumination from its reflection on diffused objects; (iii) Exploiting illumination for developing digital light sensitive displays, capable of presenting 3D scenes with spatially varying reflectance properties. As light scattering is such a fundamental phenomenon, our envisioned new tools have applications in almost any field of science, from astronomy to microscopy, and in medicine. We plan to push the bound on the penetration depth of medical imaging devices, and allow chemists to infer more information on material decomposition through scattering. In earth science we can infer aerosol density from the scattering of sunlight in the atmosphere and ocean, a central challenge in any study of climate and pollution. In addition, we will pursue new technological developments such as light sensitive displays, offering a novel form of immersive visual experience, and new technologies of coded security cameras.

Mots-clés : computational photography,subsurface scattering acquisition,light sensitive displays
Projet ERC : OrbiDynaMIQs (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : National Research Council — Pays : Italie — Rôle : Partner
Acronyme de l'entité : CNR
Type d'entité : Recherche
Financement ERC de l'entité : 96045.56 €

The interaction between localized spins and mobile fermions underlies the transport properties of a large variety of highly correlated materials. Even a single localized spin impurity can dramatically influence the motion of many fermions in its surroundings, giving rise to one of the most remarkable phenomena in quantum many-body physics - the Kondo effect. For a finite density of localized spins, the Kondo effect competes with non-local fermion-mediated Ruderman-Kittel-Kasuya-Yosida (RKKY) interactions, providing the driving force for many intriguing phenomena such as the unconventional superconductivity and the quantum critical behavior of heavy-fermion compounds. Despite decades of investigations, fundamental issues remain concerning the dynamical and spatial properties of the Kondo effect, that are difficult to tackle in electron systems. Further, a detailed understanding of the transition between the single-impurity Kondo problem and a system of interacting impurities is still missing. In OrbiDynaMIQs, I will develop a novel experimental platform for addressing such open questions. Leveraging on recent progress in manipulating single atoms with optical tweezers, I will realize a versatile two-orbital quantum simulator based on ultracold fermionic ytterbium atoms. I will focus on the spin-orbital dynamics of single and multiple localized impurities embedded in one- and two-dimensional itinerant fermion systems. I will then investigate the emergence of RKKY interactions between localized spins, both in few-body and full lattice realizations, taking first steps in exploring a whole new range of spin-correlation phenomena in Kondo systems. The proposed approach capitalizes on the strong interlink between quantum many-body physics and precision measurements with two-electron atoms, and on my experience at the confluence of these fields. It will also facilitate studies of new two-orbital models with enlarged SU(N) symmetries beyond that of spin-1/2 electron systems.

Mots-clés : kondo physics,quantum dynamics
Projet ERC : KILL-OR-DIFFERENTIAT (Horizon 2020, appel 2019, Synergy grants)
Entité participante : Medical University of Vienna — Pays : Autriche — Rôle : CO-PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3166642.63 €

The interactions between tumor and its microenvironment are often critical to uncovering the mechanisms of tumor survival. A striking example is the recent success of immunotherapy approaches that expose tumor cells to immune attack by disrupting a specific interaction between the tumor and infiltrating lymphocytes. The tumor can also repress immune response by inducing complex interactions among dozens of immune and stromal cell types that typically make up tumor microenvironment, however those remain largely uncharacterized as we currently lack systematic approaches to uncover relevant cell-cell interactions. The alternative to killing tumor cells, either directly or through immune system, is to force them to differentiate. Such strategy is particularly promising for tumors arising due to failure of progenitor populations to follow proper differentiation cascade. Here as well, the progress has been limited by lack of understanding of specific intercellular signals that that are disrupted in tumorigenesis. We propose a systematic approach for characterizing cell-cell interactions in complex microenvironments through joint analysis of spatially-resolved and disassociated single-cell transcriptomics. We will apply it to identify inter-cellular signals and pathways that can push tumors of neural crest origin, including as pheochromocytoma (PCC), paraganglioma (PGL) and neuroblastoma (NB), towards terminal differentiation. Building on our expertise with neural crest development, we will use single-cell profiling to map individual tumor cells onto developmental trajectory of neural crest differentiation. Spatial transcriptomics analysis will then be used to identify the sources and nature of microenvironment signals that channel neural crest differentiation during normal development. Contrasting interactions in normal and tumor tissues we will then aim to identify factors, pathways or signals that would push that PCC, PGL and NB tumors towards benign state.

Mots-clés : neural crest,neuroblastoma,differentiation,cancer,single cell transcriptomics,2d transcriptomics,development,tumor,pheochromocytoma,sympatho adrenal differentiation