Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MYMOVE (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
Entité participante : Royal Netherlands Academy of Arts and Sciences — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : KNAW
Type d'entité : Recherche
Financement ERC de l'entité : 1883125.0 €

Although many immigrant children are more likely to move within the country of settlement than native born youth, little is known on the potential effects of this so called internal mobility. When does childhood internal mobility have negative consequences on an individual’s life? Are there differences in processes and consequences for those of immigrant and non-immigrant background? Do the number of moves or the reason for moving make a difference? Is the age at which moving takes place decisive and is distance relevant? Despite the fact that moving is a major stress-inducing life event, so far little is known on the potential consequences of childhood internal mobility for people of diverse immigrant origins. Given Europe’s diverse population and immigration being the key factor in population change, it is crucial to understand if, how and for whom childhood internal mobility matters. The main objective of the MYMOVE project is to advance knowledge on the relationship between childhood internal mobility and adult life chances as defined by demographic family life choices, health and well-being for those with and without immigrant background. The project makes five innovative contributions to the so far scattered literature. It will 1) comprehensively map childhood internal mobility patterns; 2) study its mid- and long-term consequences for diverse immigrant groups and the native-born; 3) cover two key outcomes that are crucial in the individual life path (demographic family behaviour and health and well-being); 4) simultaneously study different dimensions of internal mobility (number, reason, timing, distance), and 5), distinguish three levels of influence that may moderate the effect of internal mobility (the neighbourhood of origin and destination, family background, and individual characteristics). The MYMOVE project will break new ground by using unique and new longitudinal (full-) population register and survey panel data from across Europe.

Mots-clés : immigrants,internal mobility,later life outcomes,life course,demography
Projet ERC : BASILIC (Horizon 2020, appel 2017, 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 : 2000000.0 €

Although the T cell antigen receptor (TCR) occupies a central place in T cell physiology, it does not work in isolation and the signals it triggers are tuned by receptors that convey positive (costimulators) and negative (coinhibitors) informations. We lack a satisfying comprehension of the way T cells integrate such multiple inputs to make informed decisions. The proteomics-based methodology we developed around the TCR places us in a favorable situation to decode at systems-level the crosstalk between the TCR, the CD28 costimulator and the PD-1 coinhibitor signaling pathways. The novelty of our approach stems from (1) its use of primary T cells, (2) its capacity to probe the architecture and dynamics of signalosomes resulting from T cell-antigen presenting cell encounters, (3) the attention we pay to the stoichiometry of the studied signalosomes, a key parameter largely ignored in previous studies, and (4) its multidisciplinary nature straddling molecular and organismal scales. Our specific aims are: Aim 1. To understand how the TCR and CD28 signaling pathways cooperate to achieve optimal T cell responses. Aim 2. To determine whether CD28 is the sole target of the PD-1 coinhibitor. Aim 3. To determine how under inflammatory conditions CD28 functions can be superseded by those of OX40, a costimulator of the TNFR superfamily. Aim 4. To unveil how malfunctions of LAT, a key signaling hub used by the TCR, disrupt the TCR-CD28 crosstalk and result in unique pathogenic T cells that by becoming ‘autistic’ to TCR signals and addicted to CD28 signals lead to severe immunopathologies. We think that combining genetic, epigenomics, proteomics, and computational approaches creates ideal experimental conditions to understand at system-levels how TCR, costimulatory, coinhibitory and inflammatory signals are integrated during T cell clonal expansion. Although of fundamental nature, our project should help understanding the harmful role PD-1 plays during anti-tumoral responses.

Mots-clés : lymphoproliferative disorders,integrative biology,proteomics,gene editing,single cell transcriptomics
Projet ERC : SOS.aquaterra (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : Aalto University — Pays : Finlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1982113.0 €

Although the human population has quadrupled over the past century, per capita food availability is globally higher than ever - at the expense of environment: scarcity of water and land as well as exceedance of several planetary boundaries. Projected population growth and climate change will further increase the pressure on feeding the planet with sustainably managed natural resources. SOS.aquaterra takes up this challenge by identifying feasible measures to meet future food demand while staying below water and land scarcity thresholds. The project develops novel integrated modelling and data analysis methods to fully exploit the rapidly increasing global open spatio-temporal datasets together with outputs from global agrological and hydrological models. In the proposal, instead of assessing water and land scarcity separately, which is the current practice, the assessments are integrated. The second novelty in SOS.aquaterra is developing an integrated model that combines for the first time the potential of conventional and innovative measures -e.g. yield gap closure, alternative protein sources- towards increased food availability. The feasibility of these measures, within the safe operating space resulting from scarcity assessment, is explored by analogical problem solving and clustering methods. The innovative integration of measures using the latest datasets and modelling tools holds high risks, yet it significantly advances the scientific and technological state of the art to meet food demand with sustainably managed natural resources.

Mots-clés : water resources,land use optimisation,resource scarcity,food security,global change,mathematical modelling,integrated assessment and modelling,sustainable development
Projet ERC : CELLPHASE_AD (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Vlaams Instituut voor Biotechnologie — Pays : Belgique — Rôle : PI
Acronyme de l'entité : VIB
Type d'entité : Recherche
Financement ERC de l'entité : 2374997.5 €

Alzheimer disease (AD) is a major health problem worldwide. New therapies require an accelerated translation of genetic information into mechanistic insights. Given limitations of rodent models, fully humanized models are needed to capture the complexity of the disease process. Human stem cells (iPS) provide great possibilities but are largely investigated in vitro with associated limitations. Many of the novel genetic risk factors for AD are expressed in microglia and astroglia, which remains an understudied population in this classically neuron-centric field. We propose here mouse-human chimeric mouse models to test the effects of AD-associated genetic risk factors on the phenotypes of transplanted microglia and astroglia derived from patients and from genomic engineered, isogenic stem cells. The cells will be followed during disease progression in brain of wild type and of mice developing Aβ- and Tau- pathology. Using single cell transcriptomics, a dynamic view of the cell states over time is generated. In a first arm of the project, we investigate how the genetic makeup of patient derived stem cells with high and low polygenic risk scores influences pathological cell states. In the second arm of the project, we generate inducible Crisper/CAS9 iPS isogenic cell lines to manipulate rapidly and specifically the expression of 4 selected AD associated genes linked to a putative cholesterol pathway but also affecting inflammation. These cell lines will be used also in the second phase of the project when validating hypotheses generated from the extensive bioinformatics analysis of the 600.000 single human cell profiles generated. We expect to identify and validate >5 novel drug targets in the astroglia-microglia axis of AD pathogenesis. Our work provides humanized models for AD, an answer on how genetic makeup affects microglia and astroglia in an AD relevant context, and establishes a highly versatile platform to explore human genetics in human cells in vivo.

Mots-clés : alzheimer s disease,neuroinflammation,microglia,astroglia,single cell biology,polygenic risk factor
Projet ERC : Dementia (Horizon 2020, appel 2014, Proof of concept grants)
Entité participante : Erasmus MC — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Alzheimer’s disease (AD) affects worldwide ~50 million people. Preclinical research relies mainly on transgenic mouse models overexpressing mutant human proteins that are altered in <5% of AD cases (e.g. β-amyloid and tau), however, despite prominent protein aggregates, they fail to show the dramatic neurodegeneration and cognitive decline of patients, indicating that plaques and tangles may not be the only requirement for AD. Age is the most determining factor in AD, but is poorly represented in current AD models. Generating bona fide mouse models for various human DNA repair syndromes we have disclosed a very strong connection between DNA damage, repair and aging including dramatic neurodegeneration. Within the context of ERC-DamAge we discovered striking parallels in neurodegeneration, progressive cognitive decline and genome-wide expression profiles of repair-deficient Ercc1Δ/- mice and human AD. The similarities in expression profiles are an order of magnitude higher than current AD mouse models. We discovered that nutritional interventions can spectacularly delay neurodegeneration, opening realistic perspectives for combating AD and other neurodegenerative disorders. The primary goal of this application is to complete the characterization of the mouse mutants as a valid model for AD by a detailed quantitative comparison of all RNA classes of relevant brain compartments of Ercc1Δ/- mutants and AD patients. This not only provides the final PoC, but also an unparalleled resource for pathway analysis, target identification and biomarkers for monitoring disease progression and effects of any intervention. This application will be instrumental to facilitate transition to a valid AD model for pharmaceutical companies enabling development of effective medication for prevention and/or therapy. This proposal addresses a huge unmet medical need worldwide, which seriously affects QoL, challenges health care systems, and offers unprecedented socio-economical opportunities.

Mots-clés : dna damage,aging,alzheimer
Projet ERC : TAU-NOW (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Lund University — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 860192.5 €

Alzheimer’s disease (AD) poses a major challenge, as 40 million people worldwide are diagnosed with AD and there is currently no cure. AD is characterized by Aβ plaques and tau neurofibrillary tangles. Recently, several phase III clinical trials targeting the Aβ pathway have failed to reach their primary endpoints. This stresses the need for diversification of the drug portfolio. Tau pathology is a promising drug target due to its strong associations with synaptic density, atrophy and cognition. I envision two treatment options to be potentially effective in halting or slowing AD: 1) preventing the spreading of pathological tau, and 2) boosting resilience against tau pathology. Both processes are currently insufficiently understood, especially in living humans. Since a few years, AD-specific tau pathology can be measured in vivo using PET. TAU-NOW uniquely utilizes longitudinal tau PET in conjunction with functional and structural MRI, biofluid and cognitive data, to investigate mechanisms of tau spread and resilience in humans. In WP1, I will test the hypothesis that tau predominantly spreads through functionally connected regions, by relating tau PET changes over time to the functional architecture of the brain. Next, molecular (CSF) and genetic (GWAS) drivers of tau spread will be identified. On top of that, I will assess whether functional disconnection in subjects who underwent epileptic surgery (i.e. unilateral medial temporal lobe resection or corpus callosotomy) leads to an asymmetric tau PET pattern decades later. In WP2, I will investigate the functional (fMRI), molecular and genetic modifiers that render individuals resilient to tau pathology. In WP3, I will examine the consequences of tau spreading and resilience for important clinical trial outcomes like cognitive and volumetric changes over time. Altogether, TAU-NOW will enhance our understanding of tau spreading and resilience and may ultimately identify novel leads for drug discovery against AD.

Mots-clés : alzheimer s disease,spreading,resilience,neuroimaging,cognition,genetics
Projet ERC : P-CITIZENS (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : Ludwig-Maximilians-Universität München — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : LMU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1905500.0 €

Amateur theatre played a significant role in the formation of a modern concept of citizenship that emerged during the Enlightenment and took shape during the American and French Revolutions. Around the social activities enacted and texts performed a broad-based movement developed between 1780 and 1850 that, arguably, had more impact than professional theatre which has previously been the almost exclusive focus of theatre studies. In the period, non-professional theatre offered huge educative possibilities for the acquisition of skills and competences deemed essential to becoming a ‘good citizen’. For the first time, a historiographical research project will study European amateur theatre’s impact on social change. Five different case studies will bring distinct cultural and political contexts into the picture that determined ideas and practices of citizenship as well as theatre: 1) late-absolutist rule in Germany, 2) revolutionary shifts in France, 3) parliamentary rule in Great Britain, 4) reformed monarchy in Sweden, and 5) a contested republic in Switzerland. The study of amateur theatre in these regions will reveal the development of their citizen practices in regard to accessibility and agency, aesthetic education, institutionalisation and professionalization. Merging performance theory, cultural theory and institutional theory this project will connect the historical formation of citizenship to discourses on performativity and the building of identity through embodied practices. It will also help to foreground the role of non-professional theatre in the shaping of society. The key objectives of this project are: [1] to contribute to a historiographic shift by focusing on the ‘doing’ and performativity of theatre practices [2] to examine how concepts of citizenship emerged around theatre in Germany, France, Britain, Sweden and Switzerland [3] to analyse how non-professional theatre embraced and further developed concepts that helped to establish a citizen

Mots-clés : theatre history,amateur cultures,political identity
Projet ERC : ALPHA (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : University of Amsterdam — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UvA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1371682.34 €

Amazon forests contribute vital ecosystem services, including maintaining biodiversity (>10,000 tree species) and storing large amounts of carbon. Amazonia also features prominently in global climate, carbon, and vegetation models, which assume tropical forests are effectively pristine and that past human disturbance mimicked natural processes. It is now evident that recurrent human disturbance of Amazonia, like fire and deforestation, were significant in some areas. Since those disturbances likely modify subsequent vegetation dynamics - including temporarily increasing forest capacity to absorb carbon - the emerging paradigm of human disturbance is a challenge to global ecological understanding. The focus of my project is thus to reliably determine whether human disturbances occurred in locations that form the basis of global models. A key expected outcome is to either legitimize or force revision to these models of carbon sequestration potential in Amazonia. I will innovatively integrate ecological, paleoecological, archaeological, chemical and biogeographic analyses to assess the degree to which past human disturbance drives the diversity patterns and carbon dynamics observed in modern Amazonian forests. For key long-term sites across Amazonia, I will quantify the: i) time since the last fire, ii) past fire frequency, extent and intensity, iii) past vegetation change in the presence and absence of human activity, and iv) continuity of past human activity over the last 1000 years. My results will provide the first quantification of local-scale recovery processes exceeding 100 years in tropical forests, and will determine if observed forest dynamics are driven by disturbances that occurred before modern ecological surveys began. I will then quantify the extent to which past disturbances create an overestimation of carbon storage potential, driving a profound reexamination of carbon sequestration and biodiversity patterns in Amazonia.

Mots-clés : disturbance ecology,fire,cultural history
Projet ERC : CatASus (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Groningen — Pays : Pays-Bas — Rôle : Partner
Acronyme de l'entité : RUG
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1437500.0 €

Amines are crucially important classes of chemicals, widely present in pharmaceuticals, agrochemicals and surfactants. Yet, surprisingly, a systematic approach to obtaining this essential class of compounds from renewables has not been realized to date. The aim of this proposal is to enable chemical pathways for the production of amines through alcohols from renewable resources, preferably lignocellulose waste. Two key scientific challenges will be addressed: The development of efficient cleavage reactions of complex renewable resources by novel heterogeneous catalysts; and finding new homogeneous catalyst based on earth-abundant metals for the atom-economic coupling of the derived alcohol building blocks directly with ammonia as well as possible further functionalization reactions. The program is divided into 3 interrelated but not mutually dependent work packages, each research addressing a key challenge in their respective fields, these are: WP1: Lignin conversion to aromatics; WP2: Cellulose-derived platform chemicals to aromatic and aliphatic diols and solvents. WP3: New iron-based homogeneous catalysts for the direct, atom-economic C-O to C-N transformations. The approach taken will embrace the inherent complexity present in the renewable feedstock. A unique balance between cleavage and coupling pathways will allow to access chemical diversity in products that is necessary to achieve economic competitiveness with current fossil fuel-based pathways and will permit rapid conversion to higher value products such as functionalized amines that can enter the chemical supply chain at a much later stage than bulk chemicals derived from petroleum. The proposed high risk-high gain research will push the frontiers of sustainable and green chemistry and reach well beyond state of the art in this area. This universal, flexible and iterative approach is anticipated to give rise to a variety of similar systems targeting diverse product outcomes starting from renewables.
Projet ERC : SCAN (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Autonomous University of Madrid — Pays : Espagne — Rôle : PI
Acronyme de l'entité : UAM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Amines are ubiquitous across natural products, pharmaceuticals, polymers and biomolecules. The number of commercially available amines, from simple to complex, makes them one of the most accessible native functional groups. Therefore, they represent an attractive feedstock for the preparation of functionalized molecules through C-N bond activation. Nature long ago developed protocols to promote oxidative deamination reactions. Inspired by this approach, SCAN (Selective Pathways for CArbon-Nitrogen Bond Cleavage) is designed to open new directions in the field of C-N bond cleavage by unlocking the oxidative deamination pathway. To achieve this goal, the following specific objectives are proposed: 1) Design of redox-active amines capable of undergoing oxidative C-N cleavage. 2) Development of novel oxidative deaminations using photoredox and metallaphotoredox catalysis. 3) Site-selective modifications of peptides through photocatalyzed oxidative deaminations. The successful implementation will allow the use of one of the most readily available functional groups in a myriad of novel catalytic transformations, including for the first time asymmetric catalysis. The prevalence of alkyl amines in pharmaceuticals makes SCAN an ideal tool for late stage functionalization and molecular editing of complex molecules. Moreover, this reactivity could be used to achieve site-selective modifications of NH2 groups in peptides via C-N bond cleavage, which would have a profound impact in the fields of chemistry and chemical biology. Together, the conceptual novelty, the ability to pursue multiple complementary approaches at once, and the various potential applications will ensure high impact of this project in both the academic and industrial communities.

Mots-clés : amines,c n activation,transition metal catalysis,asymmetric catalysis,photocatalysis,radical chemistry,drug discovery,peptides