Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : CHIPS (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
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 : 820366.74 €

Background: Acrylamide is a chemical formed in many commonly consumed foods and beverages. It is neurotoxic, crosses the placenta and has been associated with restriction of fetal growth in humans. In animals, acrylamide causes heritable mutations, tumors, developmental toxicity, reduced fertility and impaired growth. Therefore, the discovery of acrylamide in food in 2002 raised concern about human health effects worldwide. Still, epidemiological studies are limited and effects on health of prenatal exposure have never been evaluated. Research gaps: Epidemiological studies have mostly addressed exposure during adulthood, focused on cancer risk in adults, and relied on questionnaires entailing a high degree of exposure misclassification. Biomarker studies on prenatal exposure to acrylamide from diet are critically needed to improve exposure assessment and to determine whether acrylamide leads to major diseases later in life. Own results: I have first authored a prospective European study showing that prenatal exposure to acrylamide, estimated by measuring hemoglobin adducts in cord blood, was associated with fetal growth restriction, for the first time. Objectives: To determine the effects of prenatal exposure to acrylamide alone and in combination with other potentially toxic adduct-forming exposures on the health of children and young adults. Methods: Both well-established and innovative biomarker methods will be used for characterization of prenatal exposure to acrylamide and related toxicants in blood from pregnant women and their offspring in prospective cohort studies with long-term follow-up. Risk of neurological disorders, impaired cognition, disturbed reproductive function and metabolic outcomes such as obesity and diabetes will be evaluated. Perspectives: CHIPS project will provide a better understanding of the impact of prenatal exposure to acrylamide from diet on human health urgently needed for targeted strategies for the protection of the health.

Mots-clés : epidemiology,diet,prenatal exposure,biomarkers
Projet ERC : CHIPS (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Statens Serum Institut — Pays : Danemark — Rôle : Partner
Acronyme de l'entité : SSI
Type d'entité : Recherche
Financement ERC de l'entité : 102314.26 €

Background: Acrylamide is a chemical formed in many commonly consumed foods and beverages. It is neurotoxic, crosses the placenta and has been associated with restriction of fetal growth in humans. In animals, acrylamide causes heritable mutations, tumors, developmental toxicity, reduced fertility and impaired growth. Therefore, the discovery of acrylamide in food in 2002 raised concern about human health effects worldwide. Still, epidemiological studies are limited and effects on health of prenatal exposure have never been evaluated. Research gaps: Epidemiological studies have mostly addressed exposure during adulthood, focused on cancer risk in adults, and relied on questionnaires entailing a high degree of exposure misclassification. Biomarker studies on prenatal exposure to acrylamide from diet are critically needed to improve exposure assessment and to determine whether acrylamide leads to major diseases later in life. Own results: I have first authored a prospective European study showing that prenatal exposure to acrylamide, estimated by measuring hemoglobin adducts in cord blood, was associated with fetal growth restriction, for the first time. Objectives: To determine the effects of prenatal exposure to acrylamide alone and in combination with other potentially toxic adduct-forming exposures on the health of children and young adults. Methods: Both well-established and innovative biomarker methods will be used for characterization of prenatal exposure to acrylamide and related toxicants in blood from pregnant women and their offspring in prospective cohort studies with long-term follow-up. Risk of neurological disorders, impaired cognition, disturbed reproductive function and metabolic outcomes such as obesity and diabetes will be evaluated. Perspectives: CHIPS project will provide a better understanding of the impact of prenatal exposure to acrylamide from diet on human health urgently needed for targeted strategies for the protection of the health.

Mots-clés : epidemiology,diet,prenatal exposure,biomarkers
Projet ERC : COSMIC (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Harvard University — Pays : Etats-Unis — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 0.0 €

Background: One of the major challenges for malaria control and elimination is the phenomenally efficient spread of malaria through sexual stage malaria parasites (gametocytes). The epidemiology and dynamics of gametocytes are poorly understood: it is presently unknown when commitment to gametocytes first occurs during infections and what intrinsic or extrinsic factors influence gametocyte production and infectivity to mosquitoes. I hypothesize that continuous early commitment to gametocyte production and the preferential sequestration of mature gametocytes in the subdermal vasculature are key to explaining the high efficiency of malaria transmission. Aim: This proposal has three main aims: i) to determine when commitment to gametocyte production first occurs during experimental and natural infections; ii) to delineate environmental triggers that stimulate gametocyte production in the absence and presence of treatment; iii) to quantify the differential distribution of parasite developmental stages in different compartments of the human bloodstream. Approach: We will use novel parasite stage composition assays in combination with epidemiological methods to determine the dynamics of gametocyte commitment and maturation during controlled malaria infections in malaria-naive volunteers and during naturally acquired malaria infections in cohorts exposed to malaria in Burkina Faso. A stage-specific immunohistochemistry assay will, for the first time, directly quantify malaria stage composition in the subdermal vasculature and mosquito bloodmeals and allow comparison with other compartments of the circulation. Importance and Innovation: This is the first study to comprehensively characterize gametocyte commitment, maturation and infectivity in experimental and natural infections. This proposal will provide insight in one of the most important questions for malaria elimination: what processes are responsible for the phenomenally efficient transmission of malaria.

Mots-clés : malaria,gametocytes,transmission,infectivity,anopheles,mosquito,sequestration,elimination
Projet ERC : PlasmoSilencing (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
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 : 2413510.05 €

Background: The human protozoan malaria parasite P. falciparum causes approximately 200 million infections and 0.7 million deaths (mainly children) per year. In the well-studied asexual blood stages, cyclic monocistronic gene activation occurs at the transcriptional level; however, relatively few transcription factors have been identified, thus other types of regulatory processes that contribute to this coordinated gene expression are believed to exist. Through the study of molecular process of monoallelic expression of immune evasion genes in P. falciparum (project funded by a previous ERC grant to A. Scherf), we discovered an entirely new mechanism of gene silencing. We demonstrated that an exoribonuclease silences genes linked to severe malaria. A non-canonical 3’-5’exoribonuclease termed PfRNase II destroys nascent RNA made from promoter regions, leading to cryptic unstable mRNA. Parasites carrying a deficient PfRNase II produce full-length mRNA and long noncoding RNA. The molecular events and the number of genes directly controlled by this novel type of posttranscriptional gene silencing remain elusive. Aim: This proposal aims to investigate the molecular mechanisms controlling PfRNase II-dependent gene silencing using innovative strategies such as the new genome editing technique (Cas9/CRISPR) developed in my laboratory for use in P. falciparum. We will study i) the recruitment of PfRNase II to promoter regions of severe malaria related genes using protein pull-down assays and ii) the genome occupancy of PfRNase II and two other 3’-5’ exoribonucleases to determine the total number of genes controlled by this mechanism. Impact: This project represents a major change in mainstream malaria parasite gene regulation paradigms with repercussions for other organisms. The proposed research will both open new avenues in molecular process that control severe malaria and appeal to young researchers to join this rather ‘untouched’ topic.

Mots-clés : plasmodium,cryptic unstable rna,gene silencing,rnase degradation
Projet ERC : FatTryp (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : University of Lisbon — Pays : Portugal — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2000000.0 €

Background: The study of protozoan pathogens has been extensively explored often motivated to find suitable targets for new intervention strategies. However these studies have been mostly limited to those life-cycle stages that can be cultivated in vitro. Using a mouse model of African trypanosomiasis, we have recently discovered that the adipose tissue (fat) is a major reservoir for the extracellular protozoan Trypanosoma brucei and that, within this environment, parasites become phenotypically different from those in the blood. Our study exposed novel biology of the T. brucei life cycle, yet it remains unknown how parasites adapt to the fat and how parasite fat tropism affects disease. Our first aim is to determine the molecular and cellular mechanisms underlying T. brucei fat tropism. We will perform a genetic screen in mice to identify key parasite genes required for establishing and maintaining chronic infection in the fat. Together with the information of the transcriptome and proteome, we will identify the mechanistic steps underlying parasite tissue-adaptation. Our second aim is to identify the consequences of T. brucei fat tropism for the host and the importance for disease. We will first investigate if parasites can egress from the fat. We will also determine if parasites induce lipid breakdown in the host, leading to loss of fat mass. Finally, we will measure the impact of fat tropism in general traits of disease, including host survival and transmission potential. Impact: This project represents a completely novel research avenue built on recent work from my laboratory. By uncovering fundamental aspects of the biology of T. brucei, we will also improve the understanding of clinically relevant features of African trypanosomiasis, including relapses and weight loss. In addition, since parasite fat tropism has also been observed in malaria and Chagas’ disease, our findings will help elucidate disease mechanisms relevant to other infectious diseases.

Mots-clés : adipose tissue,gene expression,metabolism,trypanosoma brucei,tropism
Projet ERC : DONORS (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
Entité participante : Vrije Universiteit Amsterdam — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : VU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1252720.0 €

Background: Why do individuals repeatedly help strangers even when this incurs personal costs? Current evidence on prosocial behaviour is contradictory, scattered across disciplines, restricted to one-country studies, not taking into account contextual influences, and fails to capture its dynamic nature. An integrated model is needed to increase understanding of prosociality as a societal core value. Aim: To break with monodisciplinary approaches, and grasp the dynamic and contextual nature of prosocial behaviour, I propose a life course model to link individual determinants, social network characteristics and societal contexts. I will test the model in the case of blood donation, as example of real world prosociality where a stranger is helped at a donor’s personal costs. Approach: DONORS comprises three interlinked work packages. 1) Dynamic interplay among individual and network determinants of donor behaviour over the life course. 2) Genetic determinants of prosociality. 3) Contextual variation in donor behaviour. To validate my model, I use six unique, complementary datasets, including prospective, retrospective, country-comparative survey, genetic and registry data. Innovation: 1) A multidisciplinary view —including demography, sociology, psychology— within a dynamic life course approach to enhance theory building. 2) A multi-method design, linking sociological survey with objective health-registry data and combining psychosocial with genetic data. 3) Using country-comparisons to account for the societal contexts in which donor behaviour occurs. Impact: DONORS will inspire a new era of multidisciplinary research on prosocial behaviour. With backgrounds in Medicine, Social Sciences and Psychology, years of experience in science and practice and high-level, award-winning international publications, I am uniquely suited to combine insights from social and health sciences to set the stage for a comprehensive, innovative scientific view on donor behaviour.

Mots-clés : life course approach,blood  donor behaviour,behavioural genetics,country comparison
Projet ERC : CollectSwim (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : École polytechnique — Pays : France — Rôle : PI
Acronyme de l'entité : X
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1497698.0 €

Bacteria are tiny; yet their collective dynamics generate large-scale flows and profoundly modify a fluid’s viscosity or diffusivity. So do autophoretic microswimmers, an example of active microscopic particles that draw their motion from physico-chemical exchanges with their environment. How do such ``active fluids'' turn individual microscopic propulsion into macroscopic fluid dynamics? What controls this self-organization process? These are fundamental questions for biologists but also for engineers, to use these suspensions for mixing or chemical sensing and, more generally, for creating active fluids whose macroscopic physical properties can be controlled precisely. Self-propulsion of autophoretic swimmers was reported only recently. Major scientific gaps impair the quantitative understanding of their individual and collective dynamics, which is required to exploit these active fluids. Existing models scarcely account for important experimental characteristics such as complex hydrodynamics, physico-chemical processes and confinement. Thus, these models cannot yet be used as predictive tools, even at the individual level. Further, to use phoretic suspensions as active fluids with microscopically-controlled properties, quantitatively-predictive models are needed for the collective dynamics. Instead of ad-hoc interaction rules, collective models must be built on a detailed physico-mechanical description of each swimmer’s interaction with its environment. This project will develop these tools and validate them against experimental data. This requires overcoming several major challenges: the diversity of electro-chemical processes, the confined geometry, the large number of particles, and the plurality of interaction mechanisms and their nonlinear coupling. To address these issues, rigorous physical, mathematical and numerical models will be developed to obtain a complete multi-scale description of the individual and collective dynamics of active particles.

Mots-clés : active fluids,synthetic microswimmers,collective dynamics,hydrodynamics
Projet ERC : DecodingInfection (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499999.0 €

Bacterial pathogens remain a significant threat to global health, necessitating a better understanding of host-pathogen biology. While various evidence point to early infection as a key event in the eventual progression to disease, our recent preliminary data show that during this stage, highly adaptable and dynamic host cells and bacteria engage in complex, diverse interactions that contribute to well-documented heterogeneous outcomes of infection. However, current methodologies rely on measurements of bulk populations, thereby overlooking this diversity that can trigger different outcomes. This application focuses on understanding heterogeneity during the first stages of infection in order to reduce the complexity of these interactions into informative readouts of population physiology and predictors of infection outcome. We will apply multiparametric single-cell analysis to obtain an accurate and complete description of infection with the enteric intracellular pathogen Salmonella of macrophages in vitro, and in early stages of mice colonization. We will characterize the molecular details that underlie distinct infection outcomes of individual encounters, to reconstruct the repertoire of host and pathogen strategies that prevail at critical stages of early infection. We propose the following three objectives: (1) Develop methodologies to simultaneously profile host and pathogen transcriptional changes on a single cell level; 2) Characterizing the molecular details that underlie the formation of subpopulations during macrophage infection; and (3) Determine how host and pathogen encounters in vivo result in emergence of specialized subpopulations, recruitment of immune cells and pathogen dissemination. We anticipate that this work will fundamentally shift our paradigms of infectious disease pathogenesis and lay the groundwork for the development of a new generation of therapeutic agents targeting the specific host-pathogen interactions ultimately driving disease.

Mots-clés : host pathogen interactions
Projet ERC : DiStRes (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Université Libre de Bruxelles — Pays : Belgique — Rôle : PI
Acronyme de l'entité : ULB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Bacterial “superbugs”, refringent to antibiotic treatments, have rapidly increased with the turn of the century. Slow growing, dormant cells (known as persisters) are subpopulations of bacteria that tolerate antibiotics and are considered a primary source of infections for antibiotic-resistant pathogens since they are difficult to eradicate in conventional ways. Mutations in RelA/SpoT (RSH), the effectors of the stringent response, promote antibiotic tolerance and persistent infections and are commonly selected in clinical settings of a variety of pathogens. However, despite the importance of the RSH-mediated stringent response, there is no comprehensive knowledge on the inner workings of the enzymes, or drugs that modulate the bacterial response to stress. Modern structurally biology is currently in the midst of a revolution comparable to that of the Genomic breakthrough of the end last century. This has facilitated access to structural information and increased the accuracy of the modeling and design of de novo structures of proteins and small molecules. Thus my overarching goal is to target key steps in the molecular mechanisms of ppGpp synthesis and hydrolysis catalysed by RSH enzymes, to discover active compounds against persisters. The highlight of this proposal is a new system biology approach that combines cellular microbiology (at a single cell resolution) with structural engineering, biophysical, biochemical and chemical-biology methods to design, screen and validate novel small molecule drug candidates targeting the stringent response. Based on preliminary keystone results from my group, we devised a proof of concept experiment for which we designed a catalogue of novel modulators of the stringent response customized to target bacteria in a specific or broad spectrum way. The success of this exercise guarantees this strategy will not only deliver new antipersister compounds and biotech tools, but will also impinge fundamental research in microbiology.

Mots-clés : drug discovery,system biology,bacteria,persistence,antibiotics,rela,spot,ppgpp,macromolecular engineering
Projet ERC : APMPAL-HET (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : Fundació markets, organizations and votes in economics — Pays : Espagne — Rôle : Partner
Acronyme de l'entité : Fundació move
Type d'entité : Recherche
Financement ERC de l'entité : 634165.99 €

Based on the APMPAL (ERC) project we continue to develop the frameworks of internal rationality (IR) and optimal signal extraction (OSE). Under IR investors/consumers behave rationally given their subjective beliefs about prices, these beliefs are compatible with data. Under OSE the government has partial information, it knows how policy influences observed variables and signal extraction. We develop further the foundations of IR and OSE with an emphasis on heterogeneous agents. We study sovereign bond crisis and heterogeneity of beliefs in asset pricing models under IR, using survey data on expectations. Under IR the assets’ stochastic discount factor depends on the agents’ decision function and beliefs; this modifies some key asset pricing results. We extend OSE to models with state variables, forward-looking constraints and heterogeneity. Under IR agents’ prior beliefs determine the effects of a policy reform. If the government does not observe prior beliefs it has partial information, thus OSE should be used to analyse policy reforms under IR. If IR heterogeneous workers forecast their productivity either from their own wage or their neighbours’ in a network, low current wages discourage search and human capital accumulation, leading to low productivity. This can explain low development of a country or social exclusion of a group. Worker subsidies redistribute wealth and can increase productivity if they “teach” agents to exit a low-wage state. We build DSGE models under IR for prediction and policy analysis. We develop time-series tools for predicting macro and asset market variables, using information available to the analyst, and we introduce non-linearities and survey expectations using insights from models under IR. We study how IR and OSE change the view on macro policy issues such as tax smoothing, debt management, Taylor rule, level of inflation, fiscal/monetary policy coordination, factor taxation or redistribution.

Mots-clés : heterogeneous agents,asset pricing,fiscal policy,monetary policy,subjective investor expectations,inequality