Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : PRiSM (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 1500000.0 €

Sensory perception has recently emerged as a master regulator of integrative physiology and behavior, including feeding, by controlling fundamental and pleiotropic regulatory processes of energy and glucose homeostasis. Further, sensory perception is altered in obesity and type 2 diabetes, and childhood obesity correlates with early sensory deficit. Along this line, the discovery of the developmental origins of health and diseases revealed that metabolic diseases have recognized roots in the very early stages of life and can be predisposed to by changes in the perinatal hormonal and nutritional environments, such as occur in cases of maternal obesity and unhealthy diet. In this context, an accumulating body of evidence suggests that maternal health and nutrition could negatively impinge on the development of sensory perception, and subsequently, on the lifelong regulation of sensory-dependent control of metabolic, physiological, and behavioral regulatory processes. This innovative research program consists of four autonomous but complementary projects aimed at (1) deciphering the exact central regulatory processes mediating sensory control of feeding behavior and glucose homeostasis, (2) uncovering the influence of maternal health and nutrition on lifelong sensory regulation of metabolism, and (3) & (4) investigating two independent, yet synergistic, mechanisms that could mediate developmental programming of sensory metabolic regulation. This research program will employ a technology framework of physiological, behavioral, and developmental analyses in mice in concert with state-of-the-art systems neuroscience approaches, including optogenetics, chemogenetics, and in vivo calcium imaging. Collectively, the overarching goals of this research program are to provide new insights into the precise regulatory processes of sensory metabolic regulation and to shed light on critical basic mechanisms underlying the developmental programming of metabolic diseases.

Mots-clés : obesity,developmental programming,feeding behaviour
Projet ERC : 5HTCircuits (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Champalimaud Foundation — Pays : Portugal — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2486074.0 €

Serotonin (5-HT) is a central neuromodulator and a major target of therapeutic psychoactive drugs, but relatively little is known about how it modulates information processing in neural circuits. The theory of predictive coding postulates that the brain combines raw bottom-up sensory information with top-down information from internal models to make perceptual inferences about the world. We hypothesize, based on preliminary data and prior literature, that a role of 5-HT in this process is to report prediction errors and promote the suppression and weakening of erroneous internal models. We propose that it does this by inhibiting top-down relative to bottom-up cortical information flow. To test this hypothesis, we propose a set of experiments in mice performing olfactory perceptual tasks. Our specific aims are: (1) We will test whether 5-HT neurons encode sensory prediction errors. (2) We will test their causal role in using predictive cues to guide perceptual decisions. (3) We will characterize how 5-HT influences the encoding of sensory information by neuronal populations in the olfactory cortex and identify the underlying circuitry. (4) Finally, we will map the effects of 5-HT across the whole brain and use this information to target further causal manipulations to specific 5-HT projections. We accomplish these aims using state-of-the-art optogenetic, electrophysiological and imaging techniques (including 9.4T small-animal functional magnetic resonance imaging) as well as psychophysical tasks amenable to quantitative analysis and computational theory. Together, these experiments will tackle multiple facets of an important general computational question, bringing to bear an array of cutting-edge technologies to address with unprecedented mechanistic detail how 5-HT impacts neural coding and perceptual decision-making.
Projet ERC : ZPR (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : University of Porto — Pays : Portugal — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1497520.0 €

Several human pancreatic diseases have been characterized, being the diabetes the most common. Like others, this genetic disease is related to disrupted non-coding cis-regulatory elements (CREs) that culminate in altered gene expression. Although Genome Wide Association Studies support this hypothesis, it’s still unclear how mutations on CREs contribute to disease. The translation from the “non-coding code” to phenotype is an exciting and unexplored field that we will approach in this project with the help of the zebrafish as a suitable animal model. We aim to uncover the implications of the disruption of pancreas CREs and how they contribute to diabetes in vivo. For this we will study transcriptional regulation of genes in zebrafish. The similarities between zebrafish and mammal pancreas and the evolutionary conservation of pancreas transcription factors (TF) make it an excellent model to approach and study this disease. In this project we will characterize the zebrafish insulin producing beta-cell regulome, by determining the active CREs in this cell type and their bound TFs. Then we will compare this information with a similar dataset recently available for human beta-cells, to define functional orthologs in these species. Selected CREs will be tested by in vivo gene reporter assays in zebrafish, focusing on those functionally equivalent to human CREs where risk alleles have been associated with diabetes or those regulating genes involved in diabetes. Later these CREs will be mutated in the zebrafish genome to validate their contribution to diabetes. Finally we will translate this to predict new human disease-associated CREs by focusing on the regulatory landscape of diabetes-associated genes, without the need of having countless patients to uncover them. With this project we will create a model system that will allow the identification of new diabetes-associated CREs, which might have a great impact in clinical management of this epidemic disease.

Mots-clés : pancreas regulome,diabetes,enhancers,beta cells,zebrafish,cis regulatory elements,genome wide association studies,chip seq,atac,4c seq,crispr,cas9,pancreatic transcription factors
Projet ERC : FIRST LIGHT (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe sciences
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2458405.0 €

Several hundred million years after the Universe was born the first stellar systems began to shine. Energetic photons from early hot stars, free from enrichment by heavy elements, reionised the hydrogen in deep space. Ambitious observational facilities will directly chart this final frontier in cosmic history and any insight we can obtain now will be invaluable in future planning. Key questions include: what is the duration of this reionisation period; was this `cosmic dawn’ a brief or extended process; and what physical processes governed the subsequent evolution of these early galaxies? This proposal aims to trace the history and physics of cosmic reionisation by fully characterising the star-forming galaxy population during and towards the end of the reionisation era. The proposed program has three complementary themes. (i) Tracing the duration of the reionisation process by analysing diagnostic nebular emission lines in the spectra of early galaxies using radiative transfer calculations; the proposed measures can be usefully compared with independent signatures of cold gas during similar epochs determined by the European LOFAR interferometer. (ii) Determining whether star-forming galaxies are the sole agent of reionisation by addressing key uncertainties relating to the number of ionising photons they produce and the fraction that escape; this requires detailed spectroscopy of gravitationally-lensed examples. (iii) Inferring the abundance of the earliest galaxies whose direct detection is beyond reach of current facilities. Stellar masses and ages of galaxies seen at later times will be used to plan surveys in time for the upcoming launch of the James Webb Space Telescope. This research program is observationally challenging but I have demonstrated the relevant techniques are practical through pilot programmes undertaken in California. I am proposing to relocate to University College London and establish a new research effort in Europe to achieve these goals.
Projet ERC : FLIRT (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : University of Basel — Pays : Suisse — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1009351.0 €

Several important partial differential equations (PDEs) arising in the mathematical description of physical phenomena exhibit transport features: physical quantities are advected by velocity fields that drive the dynamics of the system. This is the case for instance for the Euler equation of fluid dynamics, for conservation laws, and for kinetic equations. An ubiquitous feature of these phenomena is their intrinsic lack of regularity. From the mathematical point of view this stems from the nonlinearity and/or nonlocality of the PDEs. Moreover, the lack of regularity also encodes actual properties of the underlying physical systems: conservation laws develop shocks (discontinuities that propagate in time), solutions to the Euler equation exhibit rough and "disordered" behaviors. This irregularity is the major difficulty in the mathematical analysis of such problems, since it prevents the use of many standard methods, foremost the classical (and powerful) theory of characteristics. For these reasons, the study in a non smooth setting of transport and continuity equations, and of flows of ordinary differential equations, is a fundamental tool to approach challenging important questions concerning these PDEs. This project aims at establishing: (1) deep insight into the structure of solutions of nonlinear PDEs, in particular the Euler equation and multidimensional systems of conservation laws, (2) rigorous bounds for mixing phenomena in fluid flows, phenomena for which giving a precise mathematical formulation is extremely challenging. The unifying factor of this proposal is that the analysis will rely on major advances in the theory of flows of ordinary differential equations in a non smooth setting, thus providing a robust formulation via characteristics for the PDEs under consideration. The guiding thread is the crucial role of geometric measure theory techniques, which are extremely efficient to describe and investigate irregular phenomena.

Mots-clés : transport and continuity equations,ordinary differential equations with non smooth velocities,geometric measure theory,bv functions,conservation laws,euler equations,mixing of fluids
Projet ERC : DEFOG (Horizon 2020, appel 2018, Proof of concept grants)
Entité participante : Hasselt University — Pays : Belgique — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 131563.0 €

Several organisations active in the health care market make decisions based on an estimation of the number of individuals infected with an infectious disease. These organisations benefit from a timely and trust-worthy prediction of the number of infected individuals. To date, infectious disease predictions tools are inadequate because they typically include limited and domain-specific data and because the translation to impact for specific stakeholders in the healthcare market is lacking. DEFOG proposes a data science solution as we will integrate classical surveillance data, pharmacy sales data, out-of-hours general practitioners data and social contact data in a novel real-time forecasting tool that will yield better and more rapid warning signals of the number of infected cases. DEFOG will produce software and know-how under intellectual property of the principal investigator which will be exploited through licence agreements with and consultancy services for various stakeholders. DEFOG will build on recent advances in mathematical modelling for infectious diseases as part of the original ERC-TransMID project. The team offers a vast amount of expertise in mathematical and infectious disease modelling, computational processing, business development and has an extensive collaborative network with research centres, regulatory agencies and companies, of which 4 entities already expressed interest in exploring the use and/or sharing data for of the proposed innovative real-time disease forecasting tool.

Mots-clés : infectious disease,disease burden,forecasting,software,pharmaceutical sector,pharmacies,public health,laboratories,warning signals,data science
Projet ERC : DIME (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Ghent University — Pays : Belgique — Rôle : PI
Acronyme de l'entité : UGent
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1273750.0 €

Several recent medical innovations do not conform with the way medicine traditionally operates, but rather blur the boundaries of medicine and/or side-line the doctor-patient relationship as an essential aspect of healthcare. Examples of this are healthcare apps, direct-to-consumer genetic testing, disease surveillance, electronic patient records, telehealth and certain types of clinical decision support systems. I postulate that several of these new innovations will fundamentally change the very concept of medicine and thus turn out to be disruptive innovations. Given that medical ethics are tailored to ‘traditional’ medicine, we should be critical about its current ability to cope with these changes and question whether the discipline of medical ethics is sufficiently equipped to guide new, disruptive innovations in healthcare towards their great potential in terms of improving patients’ access to good quality healthcare, while also safeguarding patients/users for the risks that come with them, not only in terms of health, but also in terms of infractions against firmly rooted values such as patient autonomy, the duty of care, confidentiality or privacy. If the medical ethics toolbox is ill-equipped to deal with these challenges, we urgently need to rethink or replace procedures, principles or theories in order to remedy this problem. DIME will address these challenges by focusing on three main objectives: (1) To establish where the most prominent ethical disruptions are located and therefore in which areas re-orientations of ethical principles are most urgently needed. (2) To develop normative arguments regarding which fundamental procedures, principles or theories in medical ethics ought to be reinforced, adapted or replaced in the face of disruptive innovations to better cope with the challenges ahead. (3) To critically analyse the shifting moral responsibilities in healthcare as a consequence of disruptive innovations.

Mots-clés : medical ethics,medical innovation,disruptive innovation,responsibility
Projet ERC : ASICA (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : University of Leeds — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 68735.0 €

Severe droughts in Amazonia in 2005 and 2010 caused widespread loss of carbon from the terrestrial biosphere. This loss, almost twice the annual fossil fuel CO2 emissions in the EU, suggests a large sensitivity of the Amazonian carbon balance to a predicted more intense drought regime in the next decades. This is a dangerous inference though, as there is no scientific consensus on the most basic metrics of Amazonian carbon exchange: the gross primary production (GPP) and its response to moisture deficits in the soil and atmosphere. Measuring them on scales that span the whole Amazon forest was thus far impossible, but in this project I aim to deliver the first observation-based estimate of pan-Amazonian GPP and its drought induced variations. My program builds on two recent breakthroughs in our use of stable isotopes (13C, 17O, 18O) in atmospheric CO2: (1) Our discovery that observed δ¹³C in CO2 in the atmosphere is a quantitative measure for vegetation water-use efficiency over millions of square kilometers, integrating the drought response of individual plants. (2) The possibility to precisely measure the relative ratios of 18O/16O and 17O/16O in CO2, called Δ17O. Anomalous Δ17O values are present in air coming down from the stratosphere, but this anomaly is removed upon contact of CO2 with leaf water inside plant stomata. Hence, observed Δ17O values depend directly on the magnitude of GPP. Both δ¹³C and Δ17O measurements are scarce over the Amazon-basin, and I propose more than 7000 new measurements leveraging an established aircraft monitoring program in Brazil. Quantitative interpretation of these observations will break new ground in our use of stable isotopes to understand climate variations, and is facilitated by our renowned numerical modeling system “CarbonTracker”. My program will answer two burning question in carbon cycle science today: (a) What is the magnitude of GPP in Amazonia? And (b) How does it vary over different intensities of drought?

Mots-clés : carbon cycle,carbon uptake,stable isotopes
Projet ERC : SEXSEA (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
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 : 1498694.89 €

Sexual reproduction is an extraordinarily widespread phenomenon that assures the production of new genetic combinations in nearly all eukaryotic lineages. Although the core mechanisms of sexual reproduction (meiosis and syngamy) are highly conserved, the control mechanisms that determine whether an individual is male or female are remarkably labile across eukaryotes. In genetically controlled sexual systems, gender is determined by sex chromosomes, which have emerged independently and repeatedly during evolution. Sex chromosomes have been studied in only a handful of classical model organism, and empirical knowledge on the origin and evolution of the sexes is still surprisingly incomplete. The goal of our project is to exploit the remarkable richness of sexual characteristics of the brown algae to gain novel insights into the functional and evolutionary interactions between the sex chromosomes and key eukaryotic reproductive and life cycle features. First, we will use the model brown alga Ectocarpus to reveal the fundamental genetic mechanisms by which sex chromosomes control reproductive and life cycle traits of broad importance to all eukaryotes, including sex determination and asexual reproduction through parthenogenesis but also the control of gamete size and the regulation of developmental switches during the life cycle. Secondly, we will employ a combination of experimental and computational approaches on selected brown algal species exhibiting a range of reproductive and life cycle features to understand the long term evolutionary consequences of the variations in these traits to the structure of their sex chromosomes, in a phylogenetic context. These analyses will not only reveal fundamental forces that shape sex chromosome evolution in the scope of the tree of life, but will also uncover the mechanisms underlying important evolutionary transitions between major reproductive and life cycle modes and shed new light on the origin and evolution of the sexes.

Mots-clés : sex chromosome evolution,sex determination,life cycle,alternation of generations,brown algae,gametophyte and sporophyte development,anisogamy,sexes
Projet ERC : RACOM (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : University of Warwick — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1421005.0 €

Silver coinage formed the backbone of state finance in Classical antiquity. The fineness and quality of a coinage is often taken by historians to be a comment on the fiscal health of the issuing state, yet very little is really known about its fineness and chemical composition, and many of the existing analyses are inadequate to answer key questions. Samples for analysis are commonly taken from the surfaces, or from just beneath the surfaces, of silver coins, and these are not representative of the original alloys used, leading to erroneous estimates of overall composition. The aim of the project is to examine financial and monetary strategies from c. 150 BCE to a major coin reform in c. 64 CE – a period that witnessed the creation of an overarching currency for the Mediterranean world and increasing monetisation – by providing a detailed and reliable set of analyses of the chemical composition of all major silver coinages of the period, obtained by taking samples from deep within the coins. It will also evaluate two new, non-destructive techniques to see how they compare with established protocols. The period witnessed a major increase in long distance trade and probably also economic growth and a rise in per capita income. Roman conquest led to greater economic and monetary integration of the Mediterranean area, and Rome’s apparent currency monopoly may have had its own consequences for the development of coinage and management of finances. Flows of precious metals to Rome and other important centres of power helped to finance Roman expansion, and understanding the chemical composition of silver coinage will transform our understanding of Roman monetary strategy as an instrument of imperialism.

Mots-clés : roman empire,coinage,monetary history,hellenistic world,scientific analysis,microwave plasma atomic emission spectrometry,inductively coupled plasma mass spectrometry,lead isotopes,metallography,laser ablation,negative muons