Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : RELYUBL (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : University of Dundee — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499987.0 €

T lymphocytes are key cells of the adaptive immune system that protect us against pathogens and malignant cells. T cell activation and differentiation are tightly controlled processes and deregulation can result in lymphomas, autoimmunity and inflammation. Hence, the biochemical events regulating lymphocyte biology have long been a topic of intense research, which has been focussed predominantly on protein phosphorylation. I hypothesize that there are crucial roles undiscovered in T cells for other posttranslational modifications (PTMs) such as ubiquitin (Ub) and Ub-like proteins (UBLs). The importance of ubiquitylation in adaptive immunity is implied by the severe immunological disorders observed when components of the Ub system are disrupted in lymphocytes. Genetic approaches in mice give a limited understanding about the roles of these modifiers and do not reveal the full extent to which Ub and UBLs regulate lymphocyte biology. Deterred by the complexity of the Ub system, the field has not yet tackled the daunting challenge of systematically investigating these modifiers in vivo. The goal of this proposal is to define how T cell function and immune responses are regulated by Ub and UBL signalling networks. To pioneer substantial progress in this area, we will develop new methods to identify and characterize currently unknown recognition modules for the different modifications. We will elucidate the Ub and UBL modified proteome in lymphocytes and characterize dynamic changes of these PTMs during T cell activation. By focussing on enzymes that remove the modifications we will discover how these PTMs are regulated and define Ub and UBL-dependent signalling nodes. Each phase of the work will deliver fundamentally novel mechanistic insights into these PTMs while rewriting current concepts of signalling in lymphocytes. Ultimately, this work will inform therapies seeking to target lymphocyte activity in disease.

Mots-clés : ubiquitin,deubiquitinases,ubiquitin like modifier,proteomics,lymphocyte activation,differentiation,posttranlational modification,lymphocyte signalling
Projet ERC : DevoTed_miR (Horizon 2020, appel 2014, 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 €

T lymphocytes display potent pro- or anti-inflammatory properties, which typically associate with distinct effector (Teff) versus regulatory (Treg) cell subsets. Based on published and our preliminary data showing a major impact of microRNAs on T cell differentiation and (auto)immune pathology, my proposal aims to dissect the miRNA networks that control the balance between Teff and Treg subsets in vivo, in various experimental models of infection and autoimmunity. We will focus on three critical mediators of T cell functions: interferon-gamma (IFN-g) and interleukin-17A (IL-17), highly pro-inflammatory Teff cytokines; and Foxp3, the transcription factor that confers Treg suppressive properties. To track the activity of these key genes, we will generate a new Ifng/ Il17/ Foxp3 triple reporter mouse, from which we will isolate Teff and Treg subsets to determine their genome-wide miRNA profiles and specific signatures in vivo. We will investigate both natural (thymic-derived and present in naïve mice) and induced (in the periphery upon challenge) Teff and Treg subsets, as they make distinct contributions to the immune response. We will identify miRNAs selectively expressed in Teff (Ifng+ or Il17+) versus Treg (Foxp3+) subsets of various lineages (CD4+, CD8+, gamma-delta or NKT) in each in vivo model; assess whether they are induced during thymic development or upon peripheral activation; and determine the robustness of subset-specific miRNA profiles across various in vivo challenges. We will then use loss- and gain-of-function strategies to define the individual miRNAs that impact Teff or Treg differentiation and disease pathogenesis; dissect the external cues and intracellular mechanisms that regulate miRNA expression; and identify the mRNA networks controlled by key miRNAs in Teff and Treg differentiation. I expect this project to provide major conceptual and experimental advances towards manipulating miRNAs either to boost immunity or to treat autoimmunity.

Mots-clés : t cell differentiation,microrna,cytokines
Projet ERC : T-CUBE (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : Ludwig-Maximilians-Universität München — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : LMU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 0.0 €

T-CUBE aims at the theoretical modeling of chemistry involving the continuum. Traditionally, chemistry has been concerned with electrons that remain bound to the nuclei during a reaction. However, in many settings that deal with X rays or plasma, electrons can enter and leave the system; they are unbound. Most theoretical approaches for unbound electrons are not applicable to extended systems in complex environments. As a consequence, pathways and product distributions of processes such as dissociative electron attachment and Coulomb explosion are poorly understood. This hinders progress in laboratory and technology: The electron is a simple and versatile catalyst, but corresponding applications are still in an infant stadium. T-CUBE seeks to overcome these limitations. Often, unbound electrons can be described by resonances, electronic states with complex-valued energy. In recent years, I contributed to advancing this approach significantly. Small molecules in gas phase can now be described with an accuracy that allows for quantitative comparison to experiment. Here, I propose to investigate the chemistry of unbound electrons in larger molecules and condensed phase, for example, in solutions, polymeric networks, and biomolecules. Aspects that we will address include: energetics and character of resonances in different environments, resulting changes in chemical reactivity, and the interplay of nuclear motion and electron loss. To achieve these goals, quantum chemistry for electronic resonances needs to be advanced substantially. We will develop electronic-structure methods suitable for over a hundred of atoms, a quantum embedding scheme for describing different environments, and molecular dynamics simulations that take into account electron loss. In addition, we will advance the theory of electronic resonances itself. In exemplary applications, we will investigate phenomena involving dissociative electron attachment, electron transfer, and Coulomb explosion.

Mots-clés : electronic resonances,electron induced chemistry,dissociative electron attachment,coulomb explosion,electronic structure theory,quantum chemistry
Projet ERC : TB-EPF (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : UK Research and Innovation — Pays : Royaume-Uni — Rôle : Partner
Acronyme de l'entité : UKRI
Type d'entité : Recherche
Financement ERC de l'entité : 1.25 €

TB is transmitted via person-to-person aerosols. Recent studies suggests that in TB endemic areas up to 70% of transmission events take place outside the household in public places. Moreover, TB transmission is unequally spatially distributed and occurs in transmission hotspot areas. Mathematical models consequently demonstrated that identifying hotspots and blocking within-hotspot-transmission through targeted public health interventions will be the most efficient way of lowering the TB burden. In the present PoC proposal we aim to complement the population-based Enhanced-Case-Finding intervention tested in the INTERRUPTB study, with a spatially more targeted “Enhanced-Place-Finding” (EPF) approach to identify transmission hotspots in an unbiased fashion. Using traditional methods to find transmission hotspots can only be done retrospectively after years of data collection. Therefore we propose a novel EPF strategy to detect transmission hotspots in real-time using phone-tracking technology to establish a spatial map of aggregated TB patients movements. Within the ERC-funded INTERRUPTB study in The Gambia, we sequenced 2000 mycobacterial isolates, which allows us to establish a bacterial genetic transmission network. Within the PoC proposal, we seek to reconsent these patients to analyze their everyday movements using classical contact investigation complemented by phone tracking, to determine which public places have an increased risk of TB transmission. We aim to demonstrate that phone tracking of TB patients can be a cheap, easy, and, most importantly, prospective TB transmission hotspots identification tool, no longer requiring molecular epidemiological investigations. Such a finding can ultimately be developed into an app that warns national TB programs of early TB outbreaks, so that early public health measures like increased ventilation and active case finding can be initiated. This approach can furthermore be applied to other infectious diseases.

Mots-clés : tuberculosis transmission hotspots case finding phone tracking
Projet ERC : TibSchol (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : Austrian Academy of Sciences — Pays : Autriche — Rôle : PI
Acronyme de l'entité : OAW
Type d'entité : Recherche
Financement ERC de l'entité : 1994161.0 €

TIBSCHOL will be the first wide-ranging exploration of the formative phase (11th–13th c.) of the Tibetan Buddhist scholastic tradition. Its ground-breaking study of an exceptionally active period of Tibetan scholarly creativity will integrate Tibetan thinkers into world intellectual history and the global history of philosophy. The revival of Buddhist culture in Tibet in the late 10th/11th c., marked by an intense engagement with the sophisticated tradition of Indian Buddhist scholarship, set in motion the development of new tools of reasoned analysis and their application in synthesizing exegeses of Indian Buddhist soteriological and philosophical literature and in newly devised textual genres. TIBSCHOL integrates the contextual aim of reconstructing the early Tibetan scholastic landscape with the conceptual aim of exploring the Tibetan scholastic method. This involves: - Mapping the networks of Tibetan scholastics in the 11th–13th c. - Charting the early scholastic corpus - Investigating seminal features of the early Tibetan scholastic toolkit - Studying how this toolkit was applied in hermeneutics and argumentation TIBSCHOL takes advantage of the recent surfacing of a large amount of early scholastic writings in manuscript form, advocating a broad-scale approach to this corpus that goes beyond previous studies both in qualitative and in quantitative terms. Introducing an original methodology that systematically exploits the high degree of intertextuality displayed in these scholastic treatises (typically containing critical discussions of others’ views), the project articulates personal networks, intellectual networks, and intellectual profiles. This will pave the way for studying the circulation of texts and knowledge propagation, as well as the continuities and ruptures in a particularly enduring tradition of methodical and systematic learning in human history, as forms of scholasticism continue to survive in Tibetan monastic contexts to the present day.

Mots-clés : scholasticism,buddhism,tibet,religion,networks
Projet ERC : TILC (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Aix-Marseille Université — Pays : France — Rôle : PI
Acronyme de l'entité : amU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2257500.0 €

TILC focuses on Innate Lymphoid Cells (ILCs). ILCs are a newly discovered type of lymphocyte, and their study opens up new perspectives for understanding and manipulating of immunity. ILCs include cytotoxic ILCs (NK cells) and helper-like ILCs (ILC1, ILC2 & ILC3). Studies of ILC2 cells have advanced considerably, but much remains unknown about the respective roles of NK, ILC1 and ILC3 cells. TILC aims to explore new frontiers in ILC biology, by focusing on these subsets of ILCs in mice and humans, through five specific aims. 1. NK cells, ILC1 & NCR+ILC3 are known to express NKp46 in humans and mice, but the nature of the NKp46 ligands remains unclear, limiting our understanding of the biology of these three major ILC subsets. We thus aim to identify the NKp46 ligands, building on our preliminary data showing that Complement Factor P (CFP, Properdin) is involved in NKp46 recognition, hence revealing an unprecedented mode of immune recognition. 2. We also aim to create new mouse models selectively targeting these ILC subsets in vivo. We will then use these models for dissecting out the selective roles of ILC subsets in two major immune functions: cancer surveillance and gut homeostasis. 3. In cancer, we will investigate the contribution of these cells to tumor editing. 4. In the intestine, we will focus on the homeostasis of the cecum and appendix. These organs were long considered to be vestiges of evolution, but our own recent findings and those of phylogenetic studies have challenged this notion. We thus aim to address the role of ILC subsets in the cecum/appendix, and determine whether these organs serve as a refuge for repopulation with commensals after dysbiosis. 5. Finally, we aim to identify patients with deficiencies in ILCs, to dissect the function of these cells in natura. From the molecular scale to that of patients, we believe that TILC will provide answers to some of the most pressing questions concerning the role and clinical potential of NKp46+ ILCs

Mots-clés : innate immunity,innate lymphoid cells,natural killer cells
Projet ERC : TRANSJIHAD (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Danish Institute for International Studies — Pays : Danemark — Rôle : PI
Acronyme de l'entité : DIIS
Type d'entité : Recherche
Financement ERC de l'entité : 1499056.0 €

TRANSJIHAD aims at advancing our understanding of one of the greatest contemporary challenges on the international agenda for peace and security, namely the ability of transnational jihadist movements to tap into local conflicts, hence escalating violence. TRANSJIHAD specifically investigates the questions of how jihadist conflicts become transnational and under what circumstances they can be contained. The project also aims at developing an interdisciplinary analytical framework, which combines micro- and macro level approaches to jihadism, drawing from both Religious Studies, Security Studies and Peace & Conflict Studies. Methodologically, TRANSJIHAD dissolves the scientific dichotomy between inside- and outside-oriented approaches to the study of transnational jihadist conflicts, widening prevailing scientific understandings of transnationalization processes. The project uniquely combines i) a quantitative examination of transnationalization processes drawing from the Religion and Armed Conflicts (RELAC) dataset based at Uppsala University, ii) comparative case studies of the mechanisms of escalation and de-escalation of jihadist conflicts across Asia, the Middle East, the Arab Peninsula and Africa focusing on the movements of Islamic State, Al-Qaeda, the Taleban, and Boko Haram, iii) securitization analyses of the macro-level conflict structures that transnational jihadist movements tap into, and finally iv) sociotheological worldview analyses of potential changes in jihadist conflict imagery during transnationalization processes. With its focus on macro-level conflict structures, TRANSJIHAD also contributes to developing a new framework for thinking about containment, providing an alternative to both the micro-level countering discourses embraced by much of the radicalization research, and the containment thinking that stems from the treatment of jihadist conflicts as civil wars in the peace and conflict literature.

Mots-clés : religious violence,macro securitization,terrorism,worldview analysis,jihadism,sociotheology,conflict escalation,peace and conflict research,radicalization,transnationalization
Projet ERC : iDODDLE (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1553850.55 €

Tackling climate change requires changes to daily life in mobility, food, homes and energy domains. Digitalisation is a major trend reshaping daily life across all these domains. The digitalisation of daily life and its impact on resource consumption and emissions has not been studied systematically. A Tackling climate change requires changes to daily life in mobility, food, homes and energy domains. Digitalisation is a major trend reshaping daily life across all these domains. The digitalisation of daily life and its impact on resource consumption and emissions has not been studied systematically. A new integrated science is needed on digitalised daily life and climate change. This new field should look across domains at generalisable mechanisms, enabling conditions and steering strategies so digitalisation helps not hinders climate action. The aim of the iDODDLE project is to develop a new thematic, cross-domain, inter-disciplinary science of digitalised daily life in support of action on climate change. iDODDLE's research activities are organised in three work packages on people (micro-level), system conditions (macro-level) and action (policy and practice), drawing on two major new cross-cutting sources of primary data collection - a sample of 80 living lab households, and a longitudinal online survey panel of 6,000 respondents in UK, Sweden and Spain. iDODDLE will: (1) understand the ways in which digitalised daily life impacts climate change, including substituting physical for digital, accessing services instead of owning goods, and integrating households into supply networks; (2) determine the conditions under which digitalised daily life has beneficial or adverse impacts on climate change, including access to infrastructure, trust and power, and technophile lifestyles; (3) develop an evidence-based programme of action for ensuring digitalised daily life helps tackle climate change, including quantitative systems analysis of energy and material flows.

Mots-clés : households,information and communication technologies  icts,energy and material flows,infrastructure,lifestyles
Projet ERC : EffectiveTG (Horizon 2020, appel 2018, 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 : 1155027.0 €

Tame geometry studies structures in which every definable set has a finite geometric complexity. The study of tame geometry spans several interrelated mathematical fields, including semialgebraic, subanalytic, and o-minimal geometry. The past decade has seen the emergence of a spectacular link between tame geometry and arithmetic following the discovery of the fundamental Pila-Wilkie counting theorem and its applications in unlikely diophantine intersections. The P-W theorem itself relies crucially on the Yomdin-Gromov theorem, a classical result of tame geometry with fundamental applications in smooth dynamics. It is natural to ask whether the complexity of a tame set can be estimated effectively in terms of the defining formulas. While a large body of work is devoted to answering such questions in the semialgebraic case, surprisingly little is known concerning more general tame structures - specifically those needed in recent applications to arithmetic. The nature of the link between tame geometry and arithmetic is such that any progress toward effectivizing the theory of tame structures will likely lead to effective results in the domain of unlikely intersections. Similarly, a more effective version of the Yomdin-Gromov theorem is known to imply important consequences in smooth dynamics. The proposed research will approach effectivity in tame geometry from a fundamentally new direction, bringing to bear methods from the theory of differential equations which have until recently never been used in this context. Toward this end, our key goals will be to gain insight into the differential algebraic and complex analytic structure of tame sets; and to apply this insight in combination with results from the theory of differential equations to effectivize key results in tame geometry and its applications to arithmetic and dynamics. I believe that my preliminary work in this direction amply demonstrates the feasibility and potential of this approach.

Mots-clés : model theory  o minimality,diophantine geometry  unlikely intersections,pfaffian functions,ordinary differential equations  complex domain,subanalytic geometry
Projet ERC : ReceptorPAINT (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
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 : 1598025.0 €

Targeting cell surface proteins to alter cellular behavior is a major aim of many therapeutics. Recently approved immunotherapeutic drugs trigger anti-tumor immunity by disrupting key cell surface proteins that guide immune cell interactions. Despite the cell surface representing a major site of drug action, its nanoscale organization remains poorly characterized. The main reason for this is largely due to technical limitations of current fluorescence and super-resolution imaging approaches, which do not allow high-throughput measurements of the spatial localization and interaction of hundreds of proteins with true single-protein- resolution on cell surfaces. We here propose to develop exactly such a disruptive capability by advancing recently developed DNA-PAINT microscopy to enable the visualization and quantification of all relevant cell surface proteins at single-protein-resolution. We will achieve this by innovating DNA-PAINT to enable isotropic 1-nm-resolution, develop DNA-based protein binders against all cell surface proteins, and devise multiplexing capabilities to resolve them with single-protein-resolution over large fields of view, reaching the ultimate goal of enabling Imaging Receptomics. We will then apply this to test the central hypothesis that surface protein architecture and patterning on immune and tumor cells dictates the outcome of their interactions. We will map the nanoscale organization of hundreds of key immunomodulatory surface proteins and their corresponding ligands on key interacting pairs of immune cells relevant to current immunotherapy approaches (dendritic cells and T cells), as well as tumor cells. This will yield fundamental insights into the molecular architecture of their interactions and potentially enable the future development of more refined “pattern”-based immunotherapeutics. Collectively, this highly multidisciplinary and novel approach has the potential to be ground-breaking across a range of research fields.

Mots-clés : super resolution microscopy,dna nanotechnology,cell surface receptors,receptor tyrosine kinases,immune checkpoints