Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : OBESITY_SPIRAL (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : Radboud University Nijmegen — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Obesity is a major threat to human health, often characterized by increased consumption of energy-dense and easy-to-eat, ‘effortless fast food’. A better understanding of effort-related motivation in obesity is important to explain why healthy lifestyle changes are often so hard to maintain. Previously, I have demonstrated the neurocognitive and neurochemical processes underlying motivational control of behaviour. However, in obesity, findings about the motivation to overcome effort costs for food reward – and associated dopamine signalling - are inconsistent, suggesting another – yet unknown - variable. Here, I am the first to suggest that this variable is chronic low-grade inflammation - as a direct result of excess body fat. Peripheral inflammation can affect the brain dopamine system to decrease effortful behaviour, enforcing the downwards spiral of obesity. However, how an elevated inflammatory tone in obesity relates to effort-based decision-making is currently unknown. Here, I aim to elucidate the neurocognitive mechanisms underlying effort-based decision-making in human obesity and the explanatory role of inflammation, using both an observational and a supplementation design with the anti-inflammatory aspirin-like drug salsalate. Moreover, I will determine the causal role of dopamine in effort-based decision-making in obesity by employing acute administration of the dopamine precursor levodopa, and I will study levodopa’s effects as a function of inflammatory tone. I will develop a novel fMRI paradigm that dissociates food reward anticipation, reward sensitivity versus effort avoidance during effort decision, effort exertion and reward consumption. Lab findings will be translated to real life with experience sampling methods. This innovative, interdisciplinary approach will elucidate the inflammation-effort link in obesity and explain inconsistent findings about dopamine abnormalities and effortful behaviour in obesity.

Mots-clés : obesity,fmri,inflammation,effort,reward,dopamine
Projet ERC : ONTOGENY (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999973.0 €

Obesity is a significant global burden that is associated with adverse health outcomes. Adults are not alone in their struggles with obesity. Children now accumulate fat at an alarming rate, making childhood obesity a major health problem. Unfortunately, we do not know enough about the pathophysiology of these conditions to propose appropriate prevention strategies and more effective therapeutic approaches. In this ERC StG proposal, our goal is to discover the developmental processes important for proper con-trol of energy homeostasis. We will study Agrp and POMC neurons, located in the arcuate nucleus of the hypothalamus, that are heavily involved with control of energy homeostasis. Agrp and POMC neu-rons have delayed postnatal development, maturing their axonal projections around the third postnatal week in rodents. Here, we will study in detail this late ontogeny of Agrp and POMC neurons. In Aim 1, we will use novel approaches to measure Agrp and POMC neuronal activity during mouse development in response to nutrients and hormones involved in energy homeostasis. In Aim 2, we will use whole-brain imaging techniques to determine the anatomical development of Agrp and POMC neuronal projec-tions. We will also study the importance of a specific neuronal circuit in neonates to the development of obesity. Finally, in Aim 3, we will identify critical molecular mechanisms involved in the ontogeny of Agrp and POMC neurons by investigating their translatome over the course of postnatal development. Overall, this project will provide novel insights into Agrp and POMC neuron development in conditions relevant to childhood obesity and metabolic dysregulation. The functional, anatomical and molecular mechanisms illuminated here will provide the foundation for future studies aimed to dissect the devel-opment of other homeostatic systems.

Mots-clés : hypothalamus,metabolism,neuronal circuits,development
Projet ERC : BALDER (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : University of Copenhagen — Pays : Danemark — Rôle : PI
Acronyme de l'entité : UCPH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Obesity is an increasing problem where the central nervous system (CNS) plays a major role by regulating food intake. This regulation is based on feedback systems from peripheral organs, including adipose tissue. Brown adipose tissue (BAT) is a subtype of adipose tissue that produces heat in response to cold by switching from an idle state to a highly energy-consuming state. BAT also secretes signalling molecules called batokines, but the biological effects of batokines on distal tissues are unclear. My overall hypothesis is that the energetic state of BAT will be communicated to the CNS, via batokines, to mediate appetite control, in a BAT-brain axis. To test this, we will establish a peptide library of human plasma peptidomes of samples collected during different states of BAT activity, combined with peptidome datasets generated from human brown fat cells using two complementary approaches: peptidomics and smORF mapping. Joining these datasets will allow us to select batokine candidates that are consistently regulated by alterations in BAT activity in plasma and brown fat cells. Using in silico approaches for peptide ranking and bioactivity prediction, we will select peptides, and create a neural bioactivity screening platform, assessing neural activity and/or plasticity. For this, we will establish 3D-cultures of appetite-regulating neurons, including human iPSC-derived AgRP and POMC neurons as well as of murine primary hypothalamic neurons. These models will be incorporated with high-content screening and imaging approaches. Successful peptides will be tested for metabolic effects in mice models, and targeted neurons and signalling pathways will be tracked down to a single cell level. All experimental data will be integrated with the in-silico data to generate a searchable online atlas of appetite regulating peptides, promoting my overall goal of discovering novel appetite-regulating circuits to identify new strategies to target obesity and its related diseases.

Mots-clés : secretome,secreted peptides,brown fat crosstalk,appetite regulation
Projet ERC : RelRepDist (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1196215.0 €

One can view the representation theory of a topological group as non-commutative harmonic analysis on the group. For compact groups this view is justified by the Peter-Weyl theorem. The relative representation theory of a group is harmonic analyses on spaces with transitive group action. I work in relative representation theory of reductive (algebraic) groups over local fields, e.g. the general linear group over the field of real numbers or the field of p-adic numbers. This theory has applications to the theory of automorphic forms, in particular to the relative trace formula. There are many similarities between the real and p-adic cases, and some results can be formulated uniformly for all local fields, but their proofs are usually specific to each type of local fields. An important tool in this theory, that is applicable for all local fields, is the analysis of equivariant distributions on the group. However, this analysis is quite different for the two kinds of fields. In the first part of this proposal I describe my ongoing work on some tools that will help to approach invariant distributions uniformly for all fields. I also propose to advance, using those tools, towards the proofs of some long-standing conjectures on density of orbital integrals, comparison of Lie algebra homologies, and classification of (non-compact) Gelfand pairs. The second part of this proposal concerns generalized Whittaker models, or equivalently harmonic analyses on the quotient of a reductive group by a unipotent subgroup. In 1987 Moeglen and Waldspurger comprehensively described the role of a representation in this harmonic analyses in terms of a certain collection of nilpotent orbits attached to this representation. This result, as well as previous results on Whittaker models have many applications in representation theory and in the theory of automorphic forms. I propose to obtain an archimedean analog of this result.

Mots-clés : representation theory,theory of distributions,microlocal analysis,harmonic analysis,relative trace formula
Projet ERC : StrainBooster (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 1998750.0 €

One global challenge of humanity in the 21st century is the shift from a petrochemical to a bio-based production of chemicals and fuels. An enabling technology towards this goal is metabolic engineering which uses computational and experimental methods to construct microbial cell factories with desired properties. While it has been shown that genetically engineered microorganisms can, in principle, produce a broad range of chemicals, novel approaches to improve the performance of those strains are urgently needed to develop economically viable bioprocesses. To this end, we propose a new metabolic design principle to rationally engineer cell factories with high performance. Supported by a recent pilot study, we postulate that suitable genetic interventions combined with mechanisms that burn (waste) an extra amount of ATP (e.g., by artificial futile cycles) will increase product yield and productivity of many microbial production strains. Key objectives of StrainBooster are therefore: (1) to use computational techniques and metabolic models to identify gene knockout strategies whose coupling with ATP wasting mechanisms can boost the performance of microbial strains and to prove in silico that those strategies exist for many combinations of substrates, products, and host organisms; (2) to develop genetic modules that can robustly increase ATP dissipation in the cell; and (3) to experimentally demonstrate the power of the proposed strategy for selected production processes with Escherichia coli. To reach these ambitious goals, an interdisciplinary approach will be pursued combining theoretical and experimental studies and making use of innovative methods from systems and synthetic biology. If successful, StrainBooster will not only establish a new and ground-breaking strategy for metabolic engineering, it will also deliver novel computational tools and genetic parts facilitating direct application of the approach to design and optimize industrial fermentation processes.

Mots-clés : metabolic engineering,computational strain design,microbial cell factories,metabolic networks,stoichiometric modeling,constraint based modeling,bio based production
Projet ERC : ITHACA (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : Ttfactor srl — Pays : Italie — Rôle : Partner
Acronyme de l'entité : Ttf
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 0.0 €

One main objective of our ERC Advanced Grant project (InMec, No 341131) was to determine how cancer stem cells (CSCs) contribute to tumour growth, and the relative impact of quiescent versus proliferative CSCs. In Acute Myeloid Leukaemia (AML), our results strongly suggest that quiescent leukaemia stem cells are critical for leukaemia maintenance and relapse after treatments. AML is an aggressive and frequently fatal hematologic malignancy. It is usually sensitive to chemotherapy at its onset, leading to disease remission in most patients; however, the majority of patient will later relapse and eventually die. Notably, leukaemia stem cells are often resistant to chemotherapy. We will use our innovative phage-display antibody screening platform to generate antibodies against AMLs. The screening will be performed directly on human AMLs growing in vivo, using an innovative mouse xenotransplantation model followed by an NGS-based antibody selection procedure. We plan to isolate antibodies that selectively recognize leukaemia stem cells, either quiescent or proliferating. Our primary goal is to develop novel therapeutic antibodies for the treatment of AMLs. This project will also indirectly confirm the hypothesis that leukaemia stem cells are the real fuel of the disease. We expect that this project will lead to quick and cheap identification, cloning and validation of human recombinant antibodies towards against AML leukemic stem cells. The use of phage display technology to isolate leukemic stem cell-specific human recombinant antibodies is to our knowledge unprecedented. The development of candidate antibodies against AMLs will be accompanied by the promotion of commercial/exploitation activities such as market and competition analyses, intellectual property management, and product and business development through the activities of our partner TTFactor.

Mots-clés : acute myeloid leukemia,therapeutic antibodies,in vivo phage display screening,leukemic stem cells
Projet ERC : iPES-3DBat (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : University of the Basque Country — Pays : Espagne — Rôle : PI
Acronyme de l'entité : UPV;EHU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 135000.0 €

One of the actual limitations of the current batteries is their rigidity and limited shape availability (cylindrical or flat). Furthermore, the manufacturing of current electrodes/cells is a long process which requires big investments for battery fabrication facilities. The idea of “iPES-3DBat” Proof of Concept grant will be to develop polymer batteries by a fast and cheap 3D printing process. Compared to the traditional planar structure of cells, 3D structuring provides different shapes as well as other advantages such as higher power density and higher energy density due to the increased surface area of electrodes. The iPES-3DBat research will be dedicated to develop 3D printable inks with the already developed energetic polymers. These new inks will be patented and used to build all polymer cell prototypes by 3D printing with different geometries, flexibility, low weight and recyclability. This new technology will target future applications in wearable electronics, medical devices, fitness, toys and other small electronic devices. After a strict market study, the creation of a spin-off will be pursued. iPES-3DBat PoC will move the polymers developed within iPES ERC grant towards the commercialization stage. This PoC will take advantage of the possibility of polymers to be processed by 3D printing. At the same time, the benefits of 3D printing will be used to develop battery prototypes in a fast way, to save money by using a cheap method, to accelerate the innovation process and shorten the time-to-market. The success of this idea will involve the development of energetic inks/materials which allow the delocalization of the manufacturing of batteries with the possibility of producing anywhere.

Mots-clés : polymeric batteries,3d printing,inks
Projet ERC : MUSTANG (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe sciences
Entité participante : Technical University of Munich — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : TUM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 226550.19 €

One of the fundamental questions in modern astrophysics is how gas is converted into stars during galaxy formation, and how this may have changed with galactic environment and cosmic time. It is widely accepted that the unknown physics of star formation (SF) in molecular clouds and feedback from massive stars represent the main uncertainties in our understanding of galaxy formation. The key open questions are: which physical mechanisms govern the time-evolution of gas towards SF and its subsequent expulsion by feedback? How do these physics change with environment or cosmic time? How did the most extreme stellar systems in the Universe (i.e. globular clusters) form at high redshift? How do the cloud-scale physics of SF and feedback connect cold dark matter cosmology to the observable galaxy population? It is now possible to answer these questions thanks to two crucial developments. (1) The latest generation of billion-euro observatories allow the necessary observational data to be taken. (2) The techniques needed to solve the problem have been developed, tested, and validated, through major theoretical efforts that I have led. These developments position me ideally to answer the above questions with a unique combination of world-leading observational data, fundamental theory, innovative analysis techniques, and state-of-the-art simulations. I will use these to formulate a multi-scale description of SF and feedback, focussing on the cloud-scale physics and advancing the field beyond the phenomenology of galactic scaling relations. I will introduce an empirically-motivated, physical model for cloud-scale SF and feedback in galaxy formation simulations, thereby overcoming their main limitation and making the crucial step of linking the observable galaxy population to cold dark matter cosmology. This ambitious programme bridges observations, theory, and simulations, and can only be realised with the human resources provided by an ERC Starting Grant.

Mots-clés : star formation,galaxy formation and evolution,globular cluster formation and evolution,galactic archaeology,interstellar medium,cloud formation and evolution,observations,numerical simulations
Projet ERC : ValueChange (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : Delft University of Technology — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : TU Delft
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2477513.0 €

One of the key insights from the philosophy of technology is that technological artifacts and sociotechnical systems are not value neutral but supports or inhibits certain values. Several philosophical accounts for understanding the embedding of values in technological artifacts have been proposed and approaches like Value Sensitive Design, Design for Values and Responsible Research and Innovation have been established for integrating values into technical design. A blind spot is, however, the possibility of value change after a sociotechnical system has been designed. For example, when many of our current energy and transportation systems were designed sustainability was not yet a central value, and we are now struggling to incorporate this value into these systems. Progress in the field is currently inhibited by the lack of a philosophical theory of value change in sociotechnical systems. This proposal fills this gap by developing such a theory. It moves beyond the start of the art by proposing a dynamic rather than a static account of values, by developing insights in the dynamics of value change, by extending analysis about the embedding of values in technical artifacts to sociotechnical systems and by developing design strategies that aim at designing sociotechnical systems that can better deal with value change. The proposal has the following more specific objectives: 1) to propose a notion of value that is applicable to sociotechnical systems and that can account for value change, 2) to develop a taxonomy and mechanisms of value change in sociotechnical systems, 3) to extend philosophical analyses of the embedding of values in technological artifacts to sociotechnical systems 4) to carry out empirical studies about value change in energy systems and robot systems to support the development of a theory of value change, and 5) to develop strategies that can better deal with value change in sociotechnical systems than current value sensitive design approaches.

Mots-clés : philosophy of technology,value sensitive design,engineering ethics,sociotechnical system,design for values,responsible innovation
Projet ERC : CORFRONMAT (Horizon 2020, appel 2017, Starting 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 : 1056664.0 €

One of the main challenges in condensed matter physics is to understand strongly correlated quantum systems. Our purpose is to approach this issue from the point of view of rigorous mathematical analysis. The goals are twofold: develop a mathematical framework applicable to physically relevant scenarii, take inspiration from the physics to introduce new topics in mathematics. The scope of the proposal thus goes from physically oriented questions (theoretical description and modelization of physical systems) to analytical ones (rigorous derivation and analysis of reduced models) in several cases where strong correlations play the key role. In a first part, we aim at developing mathematical methods of general applicability to go beyond mean-field theory in different contexts. Our long-term goal is to forge new tools to attack important open problems in the field. Particular emphasis will be put on the structural properties of large quantum states as a general tool. A second part is concerned with so-called fractional quantum Hall states, host of the fractional quantum Hall effect. Despite the appealing structure of their built-in correlations, their mathematical study is in its infancy. They however constitute an excellent testing ground to develop ideas of possible wider applicability. In particular, we introduce and study a new class of many-body variational problems. In the third part we discuss so-called anyons, exotic quasi-particles thought to emerge as excitations of highly-correlated quantum systems. Their modelization gives rise to rather unusual, strongly interacting, many-body Hamiltonians with a topological content. Mathematical analysis will help us shed light on those, clarifying the characteristic properties that could ultimately be experimentally tested.

Mots-clés : calculus of variations,partial differential equations,spectral theory,schr dinger operators,bose einstein condensates,mott insulators,fractional quantum hall effect,fractional statistics