Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : EPICut (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : University of Bristol — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1758623.75 €

Interactions between bacteria and their viruses (bacteriophages) have led to the evolution of a wide range of bacterial mechanisms to resist viral infection. The exploitation of such systems has produced true revolutions in biotechnology; firstly, the restriction-modification (RM) enzymes for genetic engineering, and secondly, CRISPR-Cas9 for gene editing. This project aims to unravel the mechanisms and consequences of prokaryotic immune systems that target covalently-modified DNA, such as base methylation, hydroxymethylation and glucosylation. Very little is known about these Type IV restriction enzymes at a mechanistic level, or about their importance to the coevolution of prokaryotic-phage communities. I propose a unique interdisciplinary approach that combines biophysical and single-molecule analysis of enzyme function, nucleoprotein structure determination, prokaryotic evolutionary ecology, and epigenome sequencing, to link the molecular mechanisms of prokaryotic defence to individual, population and community-level phenotypes. This knowledge is vital to a full understanding of how bacterial immunity influences horizontal gene transfer, including the spread of virulence or antimicrobial resistance. In addition, a deeper analysis of enzyme function will support our reengineering of these systems to produce improved restriction enzyme tools for the mapping of eukaryotic epigenetics markers.
Projet ERC : FamilyTies (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
Entité participante : Université Catholique de Louvain — Pays : Belgique — Rôle : Partner
Acronyme de l'entité : UCL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 152660.0 €

Internal migration (long-distance moves within national borders) is generally assumed to be beneficial to individuals and households. This FamilyTies project has been designed to make a decisive contribution to a much more comprehensive explanation of internal migration and its labour-market outcomes than current, mainly economic, explanations have achieved thus far. It introduces a novel perspective on internal migration and immobility, which focuses on the role of family outside the household in deciding on whether and where to relocate, and which takes into account contemporary family complexity: the family ties perspective. The aim is to identify the role of family ties in internal migration, immobility and labour-market outcomes. The objectives are: 1. Identifying the role of family ties as a deterrent of migration and key determinant of immobility. 2. Explaining migration towards family in relation to migration in other directions. 3. Determining to what extent and for whom family-related motives drive migration and immobility. 4. Unravelling how individual labour-market outcomes of migration versus immobility differ between (im)mobility related to family ties and (im)mobility due to other factors. Geo-coded register and census data containing micro-links between family members will be used for Sweden, Norway, Denmark, the Netherlands and Belgium, as well as survey data for Sweden, the Netherlands, the UK, the USA and New Zealand. These will be analysed using advanced applications of hazard regression, logistic regression, OLS regression and structural equation models, which take into account the multilevel and multi-actor structure of the data and issues of endogeneity and self-selection. The project will provide major new insights into migration, immobility and labour-market outcomes, and input for better predictions and policies concerning migration, population growth and decline, ethnic segregation, labour-market flexibility and family support.

Mots-clés : internal migration
Projet ERC : FamilyTies (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
Entité participante : University of Groningen — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : RUG
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2308733.75 €

Internal migration (long-distance moves within national borders) is generally assumed to be beneficial to individuals and households. This FamilyTies project has been designed to make a decisive contribution to a much more comprehensive explanation of internal migration and its labour-market outcomes than current, mainly economic, explanations have achieved thus far. It introduces a novel perspective on internal migration and immobility, which focuses on the role of family outside the household in deciding on whether and where to relocate, and which takes into account contemporary family complexity: the family ties perspective. The aim is to identify the role of family ties in internal migration, immobility and labour-market outcomes. The objectives are: 1. Identifying the role of family ties as a deterrent of migration and key determinant of immobility. 2. Explaining migration towards family in relation to migration in other directions. 3. Determining to what extent and for whom family-related motives drive migration and immobility. 4. Unravelling how individual labour-market outcomes of migration versus immobility differ between (im)mobility related to family ties and (im)mobility due to other factors. Geo-coded register and census data containing micro-links between family members will be used for Sweden, Norway, Denmark, the Netherlands and Belgium, as well as survey data for Sweden, the Netherlands, the UK, the USA and New Zealand. These will be analysed using advanced applications of hazard regression, logistic regression, OLS regression and structural equation models, which take into account the multilevel and multi-actor structure of the data and issues of endogeneity and self-selection. The project will provide major new insights into migration, immobility and labour-market outcomes, and input for better predictions and policies concerning migration, population growth and decline, ethnic segregation, labour-market flexibility and family support.

Mots-clés : internal migration
Projet ERC : COGTOM (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : Central European University — Pays : Hongrie — Rôle : PI
Acronyme de l'entité : CEU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1179462.0 €

Internal models are fundamental to our understanding of how the mind constructs percepts, makes decisions, controls movements, and interacts with others. Yet, we lack principled quantitative methods to systematically estimate internal models from observable behaviour, and current approaches for discovering their mental representations remain heuristic and piecemeal. I propose to develop a set of novel 'doubly Bayesian' data analytical methods, using state-of-the-art Bayesian statistical and machine learning techniques to infer humans' internal models formalised as prior distributions in Bayesian models of cognition. This approach, cognitive tomography, takes a series of behavioural observations, each of which in itself may have very limited information content, and accumulates a detailed reconstruction of the internal model based on these observations. I also propose a set of stringent, quantifiable criteria which will be systematically applied at each step of the proposed work to rigorously assess the success of our approach. These methodological advances will allow us to track how the structured, task-general internal models that are so fundamental to humans' superior cognitive abilities, change over time as a result of decay, interference, and learning. We will apply cognitive tomography to a variety of experimental data sets, collected by our collaborators, in paradigms ranging from perceptual learning, through visual and motor structure learning, to social and concept learning. These analyses will allow us to conclusively and quantitatively test our central hypothesis that, rather than simply changing along a single 'memory strength' dimension, internal models typically change via complex and consistent patterns of transformations along multiple dimensions simultaneously. To facilitate the widespread use of our methods, we will release and support off-the-shelf usable implementations of our algorithms together with synthetic and real test data sets.

Mots-clés : internal model,bayesian modelling,bayesian inference,computational cognitive science,observational learning,motor learning,statistical learning,learning curve,forgetting
Projet ERC : SNUGly (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1993750.0 €

Intestinal bacteria have an enormous influence on health, both in the form of major pathogens and as major constituents of the microbiota. We have demonstrated that high-affinity secretory antibodies (sIgA) offer huge potential to protect from infection and to manipulate microbiota composition. However, designing good oral vaccines to induce high-affinity sIgA is a compound problem. Most protective anti-bacterial sIgA targets bacterial glycans, requiring an understanding of inherently difficult glycan biochemistry. We also need to deliver intact antigen via the highly degradative environment of the intestine. Whole-cell inactivated oral vaccines can induce high-affinity sIgA against some glycan structures, but we have an incomplete picture of what determines the success/failure of these vaccines. By combining advanced biophysical methods (e.g. atomic force spectroscopy), fluorescence and electron microscopy, and synthetic biology, we aim to remove this mystery. Our objectives are: 1) Generate a "toolbox" for glycan-binding antibody research: Recombinant antibodies, BCR knock-in mice and defined glycan antigens as purified molecules, on whole bacteria or on virus-like particle will be developed for model antigens: Salmonella Typhimurium O-antigen and the E.coli K100 capsule. 2) Determine the quantitative relationship between glycan antigen sampling into gut-associated lymphoid tissues and particle size, glycan flexibility/structure, digestion resistance and natural IgA binding. 3) Determine how biophysical properties of glycan antigens affect B cell antigen uptake, T cell help and antibody affinity maturation. 4) Combine models of antigen sampling efficiency and anti-glycan antibody affinity maturation to generate a systems-level model of mucosal vaccine efficacy. This will uncover the fundamental principles governing the induction of high-affinity anti-glycan sIgA, driving urgently required progress in mucosal vaccine design

Mots-clés : mucosal antibodies,oral vaccines,b cell activation,glycoconjugate vaccines
Projet ERC : GutHormones (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Roche (Switzerland) — Pays : Suisse — Rôle : PI
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 870285.31 €

Intestinal epithelium consists of self-renewing crypt-villus units and contains 6 mature cell types: Enterocytes, goblet cells, Paneth cells, Tuft cells, M cells and Enteroendocrine cells (EECs). The rare EECs are subclassified by the (>20) hormones they produce. Generally, EECs sense intestinal content and regulate gastrointestinal activity, systemic metabolism and food intake. While one EEC hormone, GLP1, has been developed into a highly successful diabetes drug, a paucity of laboratory models has complicated human EEC studies. Previously, we identified adult crypt stem cells by the novel marker Lgr5, and established conditions to grow ‘gut organoids’ from these. By single cell RNA sequencing, we have resolved the complex EEC subtype hierarchy into 5 lineages. Our studies underscore significant differences between mouse and man, not unexpected given the divergent diets and metabolism. Gut organoids can be manipulated to contain all EEC lineages. We have created a set of human organoids in which the individual hormones are fluorescently tagged by CRISPR. The current proposal exploits the technologies described above, as well as our ‘Human EEC Atlas’ to generate a detailed picture of the biology of EECs, their triggers, their interconnectivity and their products. To this end, I propose to: 1. Complete the Human EEC Atlas and hormone-tagged organoid set for stomach and colon. 2. Resolve how individual EEC subtype fates are set. 3. Resolve which luminal receptors and ligands allow sensing of nutrient components and microbial products 4. Resolve cross-regulation of EEC subtypes. 5. Investigate systemic effects of novel EEC products in mouse knockout models. Successful completion of this proposal will generate a comprehensive characterisation of EECs. This will inspire new therapeutic approaches to reshape the EEC landscape for treatment of metabolic diseases (obesity, diabetes, fatty liver disease, atherosclerosis) and other consequences of the Western-type diet.

Mots-clés : human enteroendocrine cells,organoids,hormones,microbiome
Projet ERC : Cancer-Recurrence (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Royal Netherlands Academy of Arts and Sciences — Pays : Pays-Bas — Rôle : Partner
Acronyme de l'entité : KNAW
Type d'entité : Recherche
Financement ERC de l'entité : 435606.4 €

Introduction: Current anti-cancer treatments are often inefficient, while many patients initially benefit from anti-cancer drugs eventually experience relapse of resistant tumors throughout the body. Current clinical strategies mainly aim at inducing tumor cell death, but this induction may have unintentional and unwanted side effects on surviving tumor cells. Preliminary data: We show that after chemotherapy-induced initial regression, PyMT mammary tumors reappear. During regression, we observe an increased number of cells that have undergone epithelial-mesenchymal transition (EMT) and become migratory. We show that migration can be induced upon uptake of extracellular vesicles (e.g. apoptotic bodies). Our findings suggest that EMT is induced upon chemotherapy, through e.g. EV uptake, potentially leading to migration and growth of surviving cells. Hypothesis and main aim: Based on preliminary data, we hypothesize that tumor cell death induces migration and growth of the surviving tumor cells. We aim to identify the key cell types and mechanisms that mediate this effect, and establish whether interference with these cells and mechanisms can reduce recurrence of tumors after chemotherapy. Approach: We have developed unique intravital imaging tools and genetically engineered fluorescent mice to visualize and characterize if and how dying tumor cells can affect surrounding surviving tumor and stromal cells. We will test whether dying tumor cells can influence the growth, migration, dissemination and metastasis of surviving tumor cells directly or indirectly through stromal cells. We will identify potential targets to block the influence of the dying tumor cells, and test whether this blockade inhibits the unintended side-effects of tumor cell death. Conclusion: With the studies proposed in this grant, we will gain fundamental insights on how induction of tumor cell death, the universal aim of therapy, could play a role in growth and spread of surviving tumor cells.

Mots-clés : intravital imaging,cancer imaging
Projet ERC : INFSYS (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer science and informatics
Entité participante : University of Warsaw — Pays : Pologne — Rôle : PI
Acronyme de l'entité : UW
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1340406.0 €

Investigation of infinite state systems is an active field since the early days of computer science. Despite of decades of research the most fundamental questions are not understood well even for basic models using only counters or a stack. The aim of the project is to provide solutions of the most challenging problems in the area. The goals of the project are grouped in three tasks: - The first goal in concerned with the reachability problem in Petri nets or Vector Addition Systems (VASes), a classical problem of fundamental importance. Recently, in a breakthrough paper (awarded the Best Paper Award at STOC 2019) with co-authors we have improved the lower bound for this problem from \expspace to \tower-hardness. The main goal of this task is to establish exact complexity of the reachability problem. - The second task focuses on separability problems, which ask about existence of simple classifiers. The first main goal in this task is to prove decidability of an important problem of regular separability for languages of VASes, i.e. the question whether for two given VAS languages there is a regular language including one of them and disjoint from the other one. Second main goal is to solve the word separating problem, namely to decide whether for each two words of length $n$ there exists a DFA with logarithmic number of states recognizing exactly one of them. - Without doubt the role of nondeterminism is a key question in theoretical computer science. The goal of this task is to study the related notion of unambiguity, which has very interesting properties, but is much less understood. My plan is to study unambiguity in simple models. The main goal here is to understand the complexity of the universality problem of unambiguous variants of finite automata and their extensions.

Mots-clés : infinite state systems,petri nets,vector addition systems,reachability problem,separability problem,unambiguous systems
Projet ERC : MissIons (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : University of Cologne — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499480.0 €

Ions play a key role in the chemical evolution of our universe. The process of star and planet formation is tightly connected to the presence and abundance of these species. Their spectra turn into diagnostic tools for various astrophysical environments and their temporal evolution. However, laboratory spectra of most ions relevant to astrophysics are not available. Moreover, predicted spectra from ab-initio theory are not nearly accurate enough to guide astrophysical searches. Therefore, corner stones for our understanding of chemistry in the interstellar medium are missing. In sharp contrast, highly sensitive telescopes with large collection areas are ready to find these species in space. In order to make this important next step in molecular astrophysics I propose to record high-resolution spectra from the microwave to visible range using our unique and innovative light induced reactions (LIR) methods in ion traps. It is molecule specific through mass selection, many orders of magnitude more sensitive and less complex due to buffer gas cooling as compared to conventional methods. High-resolution spectroscopy is the most accurate discipline in quantitative sciences and for molecules it is linked to highly accurate molecular structures, bond lengths and angles. But this fundamental concept is put into question for very floppy molecules, e.g. protonated methane, one of the key missing ions in space. Therefore, also new models describing the structure and internal dynamics of molecules shall be developed in this interdisciplinary project. Based on the laboratory spectroscopy in this project new molecules will be found in space. We shall unravel the role of the most important missing ions which will have great impact on the interpretation of astrophysical observations. At the same time understanding the spectra of the missing ions will challenge the current concept of molecular structure and thus lead to an advancement of molecular physics as a whole.

Mots-clés : high resoution spectroscopy,interstellar chemistry,molecular structure and,reactivity,ion molecule reactions
Projet ERC : SenSArt (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : University of Padua — Pays : Italie — Rôle : PI
Acronyme de l'entité : UNIPD
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499328.0 €

Is sight the only sense actively involved in the perception of art? This is a crucial question for Western culture, dominated today by the hegemony of vision and the suppression of the other senses. By challenging the current ocularcentric paradigm, and assimilating notions on the cultural values of sensation, SenSArt provides the first examination of medieval sacred art from the unconventional lens of its sensory agency. Between the 12th and the 15th century Europe underwent an extraordinary artistic evolution and an impressive cultural revitalization, which sparked a reassessment of the role of sensory perception in systems of knowledge and spiritual enlightenment. SenSArt explores and compares different social environments in six selected regions, pursuing three groundbreaking objectives: A) it will analyse quantitatively and qualitatively the perceptual schemes that orientated the reception of sacred art, scrutinizing how art solicited its beholders through multiple sensory inputs; B) it will develop and investigate the new notion of ‘sensory agency’ of art, establishing sacred art as a primary actor capable of exerting, through sensorial stimulation or deprivation, a social agency on its audience; C) it will provide an overall phenomenology of experiences on a European scale, by comparing the diverse patterns that different social groups lived on a local, regional and supranational scale. SenSArt will achieve its goals by developing a new combined approach at the crossroad of Art History, Philosophy and Text Studies; it will establish a multidisciplinary team of scholars to delve into a comparative set of materials, including normative texts on the senses and works of art. The project promises to bring about a paradigm shift in our understanding of Medieval Europe. It will shed new light on wide historical, devotional and cultural phenomena, outlining complex networks of social interactions where humans, art and the senses interplayed with each other.

Mots-clés : medieval art,medieval europe,spirituality,senses,sensoria