Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : UnStruct (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : Barcelona Graduate School of Economics — Pays : Espagne — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 406248.75 €

Most usable data is unstructured. Examples include text, transaction data, images, and web browsing histories. Although rich and plentiful, most economists do not use unstructured data. The few that do generally quantify it with off-the-shelf algorithms that are unrelated to the economic environment in which it is generated, which makes connecting it to economic models difficult. I instead propose to build novel probabilistic models of unstructured data that link it directly to relevant economic parameters. This powerful approach will use the information in unstructured data to test and estimate economic models in a way that is not currently possible with existing methods. I will focus on three distinct themes. The first studies how information about economic conditions is dispersed among agents, and how they aggregate it through interactions. This process it at the heart of the policymaking process, and the use of text data provides a unique opportunity to structurally model this information in innovative ways. The second theme jointly models unstructured data and the evolution of an economy hit by multiple, unobserved shocks. This will provide a novel forecasting tool, which is of key interest to policymakers. But it will also use unstructured data to estimate equilibrium models of the macroeconomy, and hence recover economic fundamentals. The final theme will use transaction payments between firms, and extend probabilistic models of network formation to create new definitions of markets that go well beyond anything in the current literature. This will contribute to measuring market power and the transmission of economic shocks, both questions of fundamental importance. Beyond these specific themes, my research will also pave the way for the use of probabilistic machine learning that combines novel data with clear economic models. The frameworks I introduce will provide a template for others to follow in the future.

Mots-clés : unstructured data,probabilistic machine learning,bayesian inference,structural modeling
Projet ERC : CiliaCircuits (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : University of Edinburgh — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1965459.94 €

Motile cilia are tiny microtubule-based projections which create fluid flow and are essential to human health. Cilia movement is powered by coordinated action of complex macromolecular motors, the axonemal dyneins. During differentiation, as cells produce hundreds of motile cilia, millions of dynein subunits must be pre-assembled in the cytoplasm into very large complexes in the correct stoichiometry which are then trafficked into growing cilia. This poses a sizeable challenge for the cell in terms of allocation of a significant fraction of the global translational machinery for streamlined assembly of dyneins within a crowded cellular space. The key question remains: How does the cell know how much is enough? This is an extreme example of a common problem in cell biology. Responsive and adaptive mechanisms must exist to prevent futile expenditure of cellular resources in making a surplus of large molecules like dyneins that may also pose a risk of toxic aggregation. While a well-defined transcriptional code for induction of cilia motility genes exists, the translational dynamics and subsequent feedback circuitry coordinating dynein pre-assembly with ciliogenesis remain unexplored. The molecular logic underlying the construction of motile cilia assembly are still not fully understood. The ambitious nature of CiliaCircuits proposes to use super-resolution and systems approaches to elucidate key mechanisms regulating this process in health and disease. Human genetics tells us that making cilia motile is a complex process. To date, almost 40 genes have been implicated in primary ciliary dyskinesia (PCD), the disease of motile cilia, for which there is no cure. The long-term vision is to understand this dynamic control operating over a specialized proteome in time and space in order to develop effective PCD therapeutics and identify additional candidate genes involved in this translation regulation.

Mots-clés : translational regulation,cilia,macromolecular assembly,axonemal dynein,mouse,ciliopathy,genome editing,super resolution imaging,disease models
Projet ERC : InfoNet (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Tel Aviv University — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1474375.0 €

Motivated by applications to information networks such as wireless and ad-hoc, this research will explore fundamental informational properties of networks under communication constraints. In the standard approach, the network is assumed to be fully connected and/or the information it carries is treated as a commodity. Here, we will investigate a markedly different paradigm where limitations on the nodes’ connectivity in the network are imposed and pieces of information can be combined. Examples include storage systems in which the links are established by physical proximity or system architecture, as well as low-power wide-area networks for Internet-of-Things applications. We will consider a broad spectrum of models and topics ranging from efficient information encoding and network resiliency to information loss under corrupt nodes to cooperative models and network information accessibility. We will study these topics under specific network families and random networks. While prominently theoretic, the proposed investigation is expected to yield insights and design rules for the construction of information networks, e.g., via new data placement techniques and communication protocols. Moreover, we plan to devote part of our study to practical aspects by implementing and testing the theory developed in real-world networks. Such developments may well lead to a paradigm shift in the design of resource-limited wireless communication systems, and potentially reduce energy consumption, delays, and increase the overall information reliability. Lastly, our motivation stems from the perception that naturally occurring phenomena in general networks are dependent on the information carried by them; this perception is what drives both the research questions we pose and the mathematical model we define. Consequently, the theoretical results are expected to be practical and influential across different disciplines and research areas.

Mots-clés : algebraic codes,erasure and error correction,corruption detection in networks,data management with topology constraints,distributed node repair on graphs,fractional decoding,random networks,threshold phenomena
Projet ERC : Descent (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Friedrich Miescher Institute — Pays : Suisse — Rôle : PI
Acronyme de l'entité : FMI
Type d'entité : Recherche
Financement ERC de l'entité : 2500000.0 €

Movement is the behavioral output of the nervous system. Animals carry out an enormous repertoire of distinct actions, spanning from seemingly simple repetitive tasks like walking to much more complex movements such as forelimb manipulation tasks. An important question is how neuronal circuits are organized and function to choose, maintain, adjust and terminate these many distinct motor behaviors. Recent technological advances in neuroscience have made it possible to begin to unravel the links between the organization of specific neuronal circuit elements in the CNS and the control of movement, a topic that will be central to this research program. While past work proposes that supraspinal centers in the brainstem are instrumental to the control of action diversification, little is known about how brainstem circuits translate movement intention to body control, how competing motor programs are selected, and how behavioral state influences movement control. The goal of this research project is to unravel the circuit blueprint of mouse descending motor pathways at a fine-scale level and to probe the intersection between revealed circuit organization and their behavioral function at many levels. The focus will be on studies on the interactions between brainstem neurons and spinal circuits to determine how initiation, duration, termination and selection of motor programs are implemented through specific neuronal subpopulations. Mapping descending connectivity matrices of motor circuits will serve as entry point and we will make use of state-of-the art intersectional technology including mouse genetics, viral approaches, in vivo neuronal recordings and activity manipulations of specific neuronal populations during behavior. Together, our project will elucidate the circuit organization and function of the descending motor output system and thereby uncover principles of how the nervous system generates diverse actions.

Mots-clés : motor system,neuronal circuit organization,mouse genetics,virual tracing
Projet ERC : DISCOVER (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499998.0 €

Multi-component systems offer the chemical and structural flexibility necessary to meet the needs of next-generation energy conversion. The vast majority of work in the field has focused on mixed-metal compounds. DISCOVER will computationally explore mixed-anion compounds. These are complex systems that provide significant technical challenges for atomistic and electronic structure modelling. Currently, structure-property relationships are poorly developed and there is a distinct lack of understanding of order-disorder transitions. Crucially, no systematic approach has been established for designing new combinations which can be tailored to match the criteria for technological applications. This project aims to utilize advanced computational techniques to: (i) understand trends in existing mixed anion systems, and (ii) to employ state of the art crystal structure prediction codes to investigate novel ternary and quaternary mixed-anion compositions. The structure-property information emanating from this analysis will allow us to develop design principles for mixed anion semiconductors, which we will use to predict prototype systems for energy conversion. Promising candidates will be experimentally tested through a collaborative network of experts in the field. This ambitious project will push the boundaries of computational materials design, through the use of both classical and electronic structure simulation techniques for bulk, surface and excited states calculations. The principle outcome will be a novel understanding of how to controllably design mixed anion semiconductors for technological applications, which will drive this material class to the forefront of materials science, while establishing my group at the frontier of computational materials science.

Mots-clés : density functional theory,defect chemistry,solid state chemistry,materials chemistry,band engineering
Projet ERC : MYELOMANEXT (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Navarra — Pays : Espagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1468606.0 €

Multiple myeloma (MM) represents a unique model to investigate cancer stem cells (CSCs), circulating tumour cells (CTCs), and the mechanisms of malignant transformation and chemoresistance. Despite the substantial improvement in MM patients’ outcome, the vast majority of patients eventually relapse and the disease remains largely incurable. For those patients failing to achieve deep remissions, biologically targeted research on the ultra-chemoresistant minimal residual disease (MRD) clone may allow us to understand the cellular mechanisms driving chemoresistance, and design novel therapeutic to overcome; importantly, such effort should be equally performed on two additional key players: CSCs and CTCs. On the opposite side, it is unquestionable that a selected group of patients does experience long-term survival irrespectively of the depth of response achieved, but we fail to understand the mechanisms driving sustained disease control. Is it because of persistent residual benign clones? Is it because of immune surveillance? Here, we will integrate next-generation flow cytometry and sequencing to define i) the signature of CTCs and ultra-chemoresistant MRD cells, ii) the hierarchical place of putative CSCs, iii) the genomic landscape of benign vs. malignant clones; and iv) the role of immune surveillance to achieve functional cures. Hence, we will characterize for the first-time-ever the highly-professional subclones responsible for malignant transformation, disease dissemination, and dramatic relapses after optimal response to therapy. Noteworthy, the innovative approach of this scientific proposal strongly relies on the use and expertise of highly-sensitive next-generation flow cytometry, coupled with optimized DNA- and RNA-sequencing for low-cell-numbers, and prospective patient samples longitudinally available within the scope of well-controlled clinical trials. Herein, we believe that all requirements are met to conduct this ground-breaking research program.

Mots-clés : multiple myeloma,minimal residual disease,circulating tumour cells,cancer stem cells,flow cytometry,next generation sequencing
Projet ERC : DIDO-MS (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : University of Perugia — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Multiple sclerosis (MS) is a chronic and progressive neurodegenerative disease that is currently affecting 2.3 million people worldwide. Incidence rates of MS are significantly higher in Europe and in other regions located within the northern hemisphere. In Europe, the number of patients currently afflicted with MS is estimated to be at 700,000, with incidence rates ranging from 2.3-12.2/100,000 per year. GlobalData assessed the market value for MS treatments in 10 major markets (France, Germany, Italy, Spain, UK, US, Canada, Japan, China and India) in 2014 to be at €16.2 billion and predicts it to rise to approximately €18.82 billion by 2024. This increase is attributed to the projected sales of newly-approved drugs. The main shortcoming of current MS treatments ultimately lies in their lack of efficacy, specifically in that they are unable to prevent progressive neurodegeneration in MS patients. MS poses a significant economic burden on society as the disease affects primarily young people who are in their most economically-productive years. Aside from limited efficacies, current treatment options are also associated with severe side-effects (increased risks of infection, cancer), high costs and inconvenient administration routes (e.g. intravenous, intramuscular, subcutaneous). The aim of DIDO-MS is to assess the commercial viability of a newly identified small molecule as a drug in the treatment of MS.

Mots-clés : multiple sclerosis,small molecule,immune modulator,treatment
Projet ERC : VIREX (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Copenhagen — Pays : Danemark — Rôle : PI
Acronyme de l'entité : UCPH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1813367.0 €

Mumps virus is a re-emerging pathogen that causes painful inflammatory symptoms, such as parotitis (salivary gland infection) and orchitis (testis infection). It is highly neurotropic with evidence of brain infection in half of cases and clinical evidence in up to 10%. It is a small RNA virus belonging to the family of paramyxoviridae that includes e.g. viruses for measles and pneumonia, all having a huge impact on global economics and human health. Current vaccine programs have not managed to eliminate mumps and infections occur also in vaccinated individuals. Seven transmembrane (7TM) receptors are important drug targets. Large DNA viruses (herpes- and pox-) assign large parts of their genomes to exploit 7TM receptors. No such mechanism has however yet been described for small viruses. Based on strong preliminary data, I will in this interdisciplinary project test the groundbreaking hypothesis that the adhesion 7TM receptor GPR125 is central for the organ damage caused by mumps virus via an interaction with the mumps virus-encoded short-hydrophobic (SH)-protein. I will do so by determining: 1 - The functional consequences of GPR125-SH-interaction at a single cell, organ and whole body level within the context of mumps virus infection 2 - The structural requirements for the GPR125-mumps virus interaction using NMR and resolution of crystal structure in preparation for future drug design The project is high risk and high gain, yet the gain clearly exceeds the risk. On account of my past expertise in pharmacology and virology, and that of several expert collaborators, the project is indeed feasible. It has tremendous perspectives as SH-proteins are present also in other viruses. The SH-GPR125 complex might thus represent a general principle for organ damage and a mode of action more generally amenable to therapeutic interference. In fact, novel approaches, mechanism-based, might be seen as more appealing to those who fear current vaccination 'modes'.

Mots-clés : molecular pharmacology,ligand receptor interaction,adhesion receptor,severe infectious diseases,virus mediated diseases,anti viral drug therapy,epithelial integrity
Projet ERC : StuDySARCOMERE (Horizon 2020, appel 2019, Synergy grants)
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : CO-PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 5000000.0 €

Muscles are specialized tissues that power voluntary, fast and coordinated movements, a hallmark of animal life. The force-generating and load-bearing devices of muscles are called sarcomeres, highly structured ensembles of many proteins. While many sub-components are structurally and functionally characterised, muscle is more than the sum of these parts: its function is highly cooperative and its structure dynamic over time and space. The high-resolution structure of sarcomeres is unknown, yet a precise molecular understanding of how the entire sarcomere machine forms and functions is required to understand its role in health, disease and ageing. This consortium will deploy an unparalleled complementary knowledge and technology base to address these fundamental and translational questions. We will solve the structure of the sarcomere at near-atomic resolution, uMuscles are specialized tissues that power voluntary, fast and coordinated movements, a hallmark of animal life. The force-generating and load-bearing devices of muscles are called sarcomeres, highly structured ensembles of many proteins. While many sub-components are structurally and functionally characterised, muscle is more than the sum of these parts: its function is highly cooperative and its structure dynamic over time and space. The high-resolution structure of sarcomeres is unknown, yet a precise molecular understanding of how the entire sarcomere machine forms and functions is required to understand its role in health, disease and ageing. This consortium will deploy an unparalleled complementary knowledge and technology base to address these fundamental and translational questions. We will solve the structure of the sarcomere at near-atomic resolution, unravel the fundamentals of its force-driven assembly and turnover in health and ageing, and develop the foundations for future basic and translational research including the design and development of new agents to mitigate muscle disease and ageing.

Mots-clés : muscle,sarcomere,structure,electron cryo tomography,nanobodies,myofibrils,nanostructure,actin,myosin,obscurin,ageing,titin,super resolution microscopy,genome editing,myofibrillogenesis,self organization
Projet ERC : StuDySARCOMERE (Horizon 2020, appel 2019, Synergy grants)
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 : 3437250.0 €

Muscles are specialized tissues that power voluntary, fast and coordinated movements, a hallmark of animal life. The force-generating and load-bearing devices of muscles are called sarcomeres, highly structured ensembles of many proteins. While many sub-components are structurally and functionally characterised, muscle is more than the sum of these parts: its function is highly cooperative and its structure dynamic over time and space. The high-resolution structure of sarcomeres is unknown, yet a precise molecular understanding of how the entire sarcomere machine forms and functions is required to understand its role in health, disease and ageing. This consortium will deploy an unparalleled complementary knowledge and technology base to address these fundamental and translational questions. We will solve the structure of the sarcomere at near-atomic resolution, uMuscles are specialized tissues that power voluntary, fast and coordinated movements, a hallmark of animal life. The force-generating and load-bearing devices of muscles are called sarcomeres, highly structured ensembles of many proteins. While many sub-components are structurally and functionally characterised, muscle is more than the sum of these parts: its function is highly cooperative and its structure dynamic over time and space. The high-resolution structure of sarcomeres is unknown, yet a precise molecular understanding of how the entire sarcomere machine forms and functions is required to understand its role in health, disease and ageing. This consortium will deploy an unparalleled complementary knowledge and technology base to address these fundamental and translational questions. We will solve the structure of the sarcomere at near-atomic resolution, unravel the fundamentals of its force-driven assembly and turnover in health and ageing, and develop the foundations for future basic and translational research including the design and development of new agents to mitigate muscle disease and ageing.

Mots-clés : muscle,sarcomere,structure,electron cryo tomography,nanobodies,myofibrils,nanostructure,actin,myosin,obscurin,ageing,titin,super resolution microscopy,genome editing,myofibrillogenesis,self organization