Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : Scaling-Sensitivity (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
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 : 2132471.0 €

All biological systems tailor their organization and properties to their size. Such size scaling is essential to The scaling of biological structures and substructures with their size is a preeminent and essential feature of life. Accordingly, the study of scaling properties had a profound impact on our understanding of animal physiology, gene expression, cell cycle regulation and intracellular dynamics. Their study at the cell level has often led to the discovery of the fundamental mechanisms allowing cells to probe their size or geometry (cell size ruler). Yet we are very far from understanding how such cell size ruler controls more macroscopic processes such as morphogenesis or global tissue size. Building on interdisciplinary methods (live-imaging, genetics, physical modeling, transcriptomics) and on the recent progresses in mechanical force sensing, we aim to understand how cell size rulers are generated in epithelial tissues and how they are modulating in time to account for the spatiotemporal regulation morphogenesis and proliferation of developing organism. More specifically, working from the cell to the tissue levels, we explore how the interplay between two fundamental and prevalent structures, actomyosin stress fibers and tricellular junctions, define an internal cell ruler probing cell size in the control of epithelial morphogenesis, signalling and proliferation. Conversely, we will explore how systemic hormonal or local tissue timers modulate such internal cell rulers to control the temporal regulation of tissue dynamics. Thereby we will understand how tissue and organismal level regulation could impact on cell size rules to control the temporal dynamics of tissues. By focusing on both the genetic and mechanical regulation at different length-scales (cytoskeleton, cell, and tissue) and time-scales (seconds to hours), we expect to provide novel and fundamental insights into the spatiotemporal mechanisms governing the dynamics of biological structures.
Projet ERC : EOLinPLACE (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
Entité participante : University of Coimbra — Pays : Portugal — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1874391.0 €

All humans die, >60% from a chronic disease. Whenever possible, this should happen where that individual feels it is the right place to be, so they feel empowered and safe. We know that most would prefer dying at home but many die in hospital. To help achieve preferences we must dig deeper. Until now, science has failed to capture the dynamics and diversity of preferences and places where people are cared for at the end of life. Current classifications of dying places are incomplete and inconsistent. I am driven by the vision of reforming the way dying places are classified and understood, refining and shifting the focus from the end-point (place of death) to the pathway that precedes it. I want to develop a strong foundation for a pioneering international classification tool that maps preferred and actual places towards death grounded on what they mean for individuals (beyond a purely physical or medical view). To achieve this I combine classic methods of developing health classifications with a bottom-up participatory research approach, working with patient and family representatives. First, I conduct a novel mixed-methods study (ethnography followed by longitudinal study) in 4 countries covering existing target variation, to explore nuances and commonalities in the experiences of patients with life-threatening conditions and their families. Based on this, I build a contemporary classification and assess its content validity in focus groups with patients, carers and other stakeholders. I then test it in varied settings to examine construct validity, reliability, responsiveness, data quality and interpretability. All data are integrated to deepen understanding of different end of life pathways in caring environments and what influences them. Prompted by my discoveries on preferences and concern with unfit classifications for a fast-growing need in a changed social world with limited care resources, my research will open new directions in how to care for the dying.

Mots-clés : place of death,patient preference,family caregiver,classification,demography,health policy
Projet ERC : CRYSTAL CLEAR (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : Utrecht University — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

All of the crystals that form in water on Earth are formed through reaction between oppositely charged ions. In these crystals, the ions are present in an ideal, charge-balanced ionic ratio. In contrast, the natural solutions in which they form, contain widely diverging ionic ratios. When crystals nucleate from natural solutions, they will be charged, and charge has a massive impact on the behaviour of small new crystals. Most nucleation experiments have been conducted in solutions with charge-balanced ionic ratios. This leads to uncharged crystal formation, which can be described with nucleation theories based on uncharged gas condensation into droplets. My pilot data show that this does not apply when ionic ratios diverge. New crystals then form and grow much slower than expected. Similarly, in natural solutions, crystals are often expected to form, but they do not, and vice versa. Clearly, we still have no idea how, why and how fast crystals nucleate in Earth surface environments. In this project, I will test the hypothesis that ionic ratio has a dramatic impact on nucleation: crystals will be charged, and this charge will determine their size, how and how fast they grow, aggregate, and transform. I will conduct state-of-the-art experiments and analyses that will provide in situ knowledge of the impact of ionic ratio on the charge, size, growth, aggregation and transformation of nuclei. Experiments will be complemented with advanced modelling to derive charged-nuclei stability and surrounding water properties. The results will be assimilated in a new crystal nucleation theory. CRYSTAL CLEAR will focus on barite, calcite and pyrite as examples of highly relevant Earth Materials. The outcome will be improved geoengineering options such as drinking water production and CO2 sequestration. My project will bring a new vision on crystal formation in nature, with radically improved predictions of rates and mechanisms, and a paradigm shift in nucleation theory.

Mots-clés : nucleation,growth,mineral transformations,colloids
Projet ERC : EpiFold (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Institute for Bioengineering of Catalonia — Pays : Espagne — Rôle : PI
Acronyme de l'entité : IBEC;IBEC-CERCA
Type d'entité : Recherche
Financement ERC de l'entité : 2499470.0 €

All surfaces of our body, both internal and external, are covered by thin cellular layers called epithelia. Epithelia are responsible for fundamental physiological functions such as morphogenesis, compartmentalization, filtration, transport, environmental sensing and protection against pathogens. These functions are determined by the three-dimensional (3D) shape and mechanics of epithelia. However, how mechanical processes such as deformation, growth, remodeling and flow combine to enable functional 3D structures is largely unknown. Here we propose technological and conceptual advances to unveil the engineering principles that govern epithelial shape and mechanics in 3D, and to apply these principles towards the design of a new generation of biohybrid devices. By combining micropatterning, microfluidics, optogenetics and mechanical engineering we will implement an experimental platform to (1) sculpt epithelia of controlled geometry, (2) map the stress and strain tensors and luminal pressure, and (3) control these variables from the subcellular to the tissue levels. We will use this technology to engineer the elementary building blocks of epithelial morphogenesis and to reverse-engineer the shape and mechanics of intestinal organoids. We will then apply these engineering principles to build biohybrid devices based on micropatterned 3D epithelia actuated through optogenetic and mechanical control. We expect this project to enable, for the first time, full experimental access to the 3D mechanics of epithelial tissues, and to unveil the mechanical principles by which these tissues adopt and sustain their shape. Finally, our project will set the stage for a new generation of biohybrid optomechanical devices. By harnessing the capability of 3D epithelia to sense and respond to chemical and mechanical stimuli, to self-power and self-repair, and to secrete, filter, digest and transport molecules, these devices will hold unique potential to power functions in soft robots.

Mots-clés : epithelia,mechanobiology,mechanotransduction,cell mechanics,micropatterning,biomechanics,biohybrid devices
Projet ERC : UreaCa (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Almost 100 years ago, Warburg described a metabolic change in energy flux that occurs during carcinogenesis. Since then, multiple studies have demonstrated how anabolic synthesis of macromolecules can be altered to support cancer cell progression. Yet, the potential effect of altered catabolic degradation of macromolecules on tumour carcinogenesis has been much less studied. The urea cycle (UC) is the main catabolic pathway by which mammals excrete waste nitrogen. Although the complete UC pathway is liver-specific, most tissues express different combinations of UC enzymes according to the cellular needs. Surprisingly, we find that changes in expression of UC components causing UC dysregulation, (UCD) is a global phenomenon in cancer, metabolically augmenting net nitrogen usage for the synthesis of macromolecules by reducing nitrogen waste. This metabolic alteration is associated with poor patient prognosis. Thus, we hypothesise that UCD provides a major metabolic advantage to multiple aspects of carcinogenesis and as such, leads to specific, identifiable genomic and biochemical signatures, with implications for cancer diagnosis and therapy. To pursue our hypothesis, we will incorporate state-of-the-art comparative genomic, peptidomic, metabolomic, and molecular approaches to explore this scientific “blind spot” of nitrogen metabolism in carcinogenesis. We will investigate how UCD causally affects carcinogenesis, by characterising tumour-specific functions of UC enzymes (Aim I), correlating tumour phenotypes with systemic biomarkers (Aim II), and testing the treatment efficacy of drug combinations targeting UCD in cancers (Aim III). Our proposal, strengthened by my training as a physician scientist, harbours considerable potential for translational diagnostic and therapeutic utility of our findings, enabling us to i) identify new diagnostic biomarkers for monitoring cancer initiation and progression and ii) predict and enhance the therapeutic response.

Mots-clés : cancer metabolism,amino acid metabolism,bio markers,immunotherapy,mutagenesis
Projet ERC : SWEETPROMISE (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Utrecht University — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Almost all cell surface proteins are modified by covalently-linked carbohydrates and the glycan structures on these glycoproteins are mediators of many physiological and disease processes. Despite their importance, there are no methods available to systematically and efficiently produce libraries of complex glycans to investigate specificities and biology of glycan binding proteins. To address this deficiency, we will develop chemoenzymatic technologies that can provide large collections of glycans having architectures of unprecedented complexity. It will exploit chemically modified sugar nucleotide donors that can be transferred by glycosyl transferases to give products in which artificial entities will blocks specific sites from enzymatic modification. It will provide full control over branching, sites of fucosylation, sulfation and sialylation. The chemical entities will be chosen in such a way that they can be removed after a series of enzymatic transformations. The methodology will be employed to prepare a series of keratan sulfate oligosaccharides. These glycoconjugates, which are biologically still poorly understood, have been implicated a multitude of physiological and disease processes. To further broaden the scope of the technology, a chemoenzymatic methodology will be developed to prepare sialosides that at C-4, C-7, C-8 and/or C-9 are modified by acetyl esters. The compounds will be used to develop a designer glycan microarray to identify ligands for glycan binding proteins. The focus will be on immuno-regulatory proteins and viruses that exploit cell surface glycans for infectivity. Cellular arrays will be developed to examine biological properties of hits identified in the microarray screening. The results of the studies will provide critical insight about glycan complexity and recognition by self- and viral glycan binding proteins, and will provide leads for the development of immune-modulators and antiviral agents.

Mots-clés : carbohydrates,oligosaccharides,enzymes,glycosyltransferases,chemoenzymatic synthesis
Projet ERC : MASCP (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Centre for Genomic Regulation — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CRG;CRG-CERCA
Type d'entité : Recherche
Financement ERC de l'entité : 2159574.0 €

Alternative splicing of messenger RNA precursors is a prevalent form of gene regulation that greatly expands the coding capacity and regulatory opportunities of higher eukaryotic genomes. It contributes to cell differentiation and pluripotency and its deregulation promotes cancer progression, as evidenced by the frequent occurrence of cancer-associated mutations in splicing factors, which are also targets of anti-tumor drugs. Despite its prevalence and relevance, the underlying mechanisms of regulation remain poorly understood. This proposal aims to develop and apply systematic approaches that can allow us to carry out the equivalent of genetic analysis of splicing regulation in cancer and pluripotent cells. These technologies can help to unweave the complex network of functional interactions within the spliceosome and of the spliceosome with regulatory factors, exhaustively map the contribution of regulatory sequences and be used to investigate, with unprecedented detail, mechanisms of regulation for essentially any regulator or alternative splicing event operating in a particular cell line. Such approaches can offer a unique opportunity to address key unresolved mechanistic questions, including the molecular basis for positional effects of splicing regulatory factors (RNA Maps), the regulatory potential of the core spliceosome and the integration of alternative splicing with other cell regulatory programs. We will combine these approaches with biochemical and cellular assays to investigate detailed mechanisms of regulation relevant for the control of cell proliferation and/or pluripotency in cancer and induced pluripotent stem (iPS) cells. Progress in this area can contribute to reveal the molecular logic governing a key layer of gene regulation and has the potential to discover novel factors and regulatory circuits that trigger or modulate cell growth, differentiation and cancer progression.

Mots-clés : pre mrna splicing,alternative splicing,regulatory mechanisms,cancer cells,stem cells,reprogramming,rna profiling,gene networks
Projet ERC : LIQUIDMASS (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : Spanish National Research Council — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 2470283.0 €

Although mass spectrometry has brought about major advancements in proteomics in the last decade, protein mass spectrometers still have important limitations. One fundamental limitation is that they require sample ionization, desorption into the gas phase and fragmentation, clearly leading to protein denaturation. Since relevant protein complexes are unstable or transient, their characterization in its native state and physiological environment remains an unexplored route towards the full understanding of protein function and protein interactions. This problem has only been targeted to date through theoretical approaches or low throughput experimental techniques, such as atomic force spectroscopy, optical tweezers or FRET. A high throughput characterization technology capable of addressing single proteins in its native state would have a large impact in proteomics. The goal of LIQUIDMASS is to develop a high throughput spectrometric technique addressing single proteins from complex samples while in physiological conditions. LIQUIDMASS also proposes a new concept for protein spectrometry, by characterizing not only the mass, but also the hydrodynamic radius, geometry and stiffness of single proteins. This multiparameter approach will serve to open up new routes to understand protein structure-function relations by providing insight into the fast conformational changes that occur in liquids. In order to attain these goals, I propose to integrate nanomechanical resonators, nano-optics and nanofluidics. The disruptive approach proposed will bring about new knowledge about protein interactions and protein conformation that is elusive today. The enabling technologies aimed at the LIQUIDMASS will increase our understanding of protein misfolding related diseases, such as Alzheimer’s or diabetes, as well as bring closer a full understanding of the human interactome, contributing to the advancement of the proteomics field.

Mots-clés : physics,chemistry,mechanical engineering,material sciences,nanotechnology,mathematics,nanofluidics,biophysics,molecular biology and proteomics
Projet ERC : FASERnu (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : University of Bern — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1998125.0 €

Although the properties of neutrinos have been intensively studied, we are still missing data about their behaviour in the TeV energy scale, as well as conclusive tests of lepton universality in neutrino scattering. Embracing the discussions on recently identified flavour anomalies, which hint at lepton universality violation, the study of high-energy neutrino interactions involving both heavy leptons and heavy quarks may be a powerful and complementary tool to search for new physics effects. Such interaction channels require high neutrino energy. Here I propose to measure high energy neutrinos with a detector sensitive to heavy flavour particles. This project (FASERnu) employs a novel approach to exploit the CERN Large Hadron Collider (LHC) as an intense neutrino source, which allows for the study of the high energy frontier of man-made neutrinos. An emulsion hybrid neutrino detector with a target mass of 1.2 tonnes will be employed. Such a detector structure has been well proven to be sensitive to heavy flavour particles: tau, charm and beauty. Data taking will be carried out during the forthcoming Run 3 of LHC operation (2021-2024), which would yield >20,000 neutrino interactions in the detector. During the timeline of this grant, neutrino cross sections will be measured for all three flavours in the uncharted energy range between 360 GeV and 6 TeV. Furthermore, the channels associated with heavy quark (charm and beauty) production will be studied. I established this project within the framework of the FASER experiment. The letter of intent and technical proposal of this project were approved by the CERN committees and I presently act as one of the project leaders of the neutrino program in FASER. FASERnu will not only investigate an unexplored energy regime, but will also provide relevant inputs to future neutrino experiments at the High-Luminosity-LHC (HL-LHC) and then at the Future Circular Collider (FCC).

Mots-clés : neutrino,flavor physics
Projet ERC : LiLa (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : Università Cattolica del Sacro Cuore — Pays : Italie — Rôle : PI
Acronyme de l'entité : UCSC;UNICATT
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1984500.0 €

Although the research area dealing with building, sharing and exploiting linguistic resources and tools for automatic processing of Latin (and, more generally, of ancient languages) has seen a large growth across the last decade, linguistic resources for Latin are still not interoperable. This means that linguistic information is split up in many products that just do not talk to each other. Such a situation results in poor exploitation of the richness provided by all those digital objects for Latin that were produced across years of work. Since Latin is a dead language (thus missing native speakers), all we can and must do is to exploit to the best the information contained in those few and precious texts that survived from the past. This means: - to make the best possible organization and use of the available linguistic resources for Latin (enhanced with web-services for Natural Language Processing – NLP –) for a fruitful integration of the information they provide, i.e. to retrieve and combine information from different sources in the most efficient way; - to make it available linguistic resources whose quality is assessed (curated data sets). The objective of the LiLa project is to connect and, ultimately, to exploit the wealth of linguistic resources and NLP tools for Latin assembled so far, in order to bridge the gap between raw language data, NLP and knowledge descriptions, thus enabling scholars to exploit to the best the currently available resources and tools. To address such a challenge, LiLa intends to incorporate the linguistic resources for Latin into the Linked Data framework, making it possible for them to be published and interlinked on the web and to interact with each other. To this aim, the project will build an open-ended knowledge base for Latin by using the Linked Data paradigm to combine data from disparate linguistic resources, provide NLP web-services and include also Latin into the multilingual Linguistic Linked Open Data cloud.

Mots-clés : latin,linked data,linguistic resources