Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : StopAutoimmunity (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Oslo — Pays : Norvège — Rôle : PI
Acronyme de l'entité : UiO
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Autoimmune disease is an increasing health concern. These diseases are strongly associated with altered gut microbiome. When immunosuppression fails there is little to offer in terms of therapy. In this project, I hypothesize that gut signals (microbial factors from the intestine) unaffected by immunosuppression are key drivers of autoimmune diseases. I propose to use recurrent autoimmune disease after organ transplantation as a human disease model to identify and stop these gut signals, providing a novel approach to close the gap between basic microbiome research and patient care in autoimmune diseases. To identify autoimmunity-related gut signals, I will use patients with primary sclerosing cholangitis (PSC), an inflammatory disease of the bile ducts. PSC is a common indication for liver transplantation, but after transplantation there is high risk of recurrent PSC (rPSC). I recently showed that the PSC gut microbiome has low diversity and identified microbial metabolites associated with severe PSC. Preliminary data show that the post-transplant gut is even less diverse, suggesting that microbial factors drive autoimmunity. In this project I will identify gut signals by in-depth investigation of gut bacterial genes and circulating metabolites in the blood. The outcome will be diagnostic and prognostic markers overlapping in PSC and rPSC, defined by changes in gut bacterial genes and concentrations of bacterial metabolites in the blood. Next, I will investigate if common drugs or interventions influence the identified autoimmunity-related gut signals. By generating a library of interventions influencing the gut microbiome it will be possible to select promising candidates for pilot treatment trials after liver transplantation. The outcome of StopAutoimmunity will be gut signals useful as novel biomarkers and treatment targets. These may directly translate into improved patient care but also provide a foundation for understanding the mechanisms of autoimmunity.
Projet ERC : EARS (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer science and informatics
Entité participante : Technion – Israel Institute of Technology — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Autonomous multi-rotor aerial vehicles (MAVs) are an emerging technology, which has a large number of current and potential applications in a wide range of industries. These airborne vehicles are becoming growingly autonomous thanks to modern artificial intelligence technologies, with their navigation and interaction capabilities based predominantly on visual sensing. While vision navigation has attracted considerable attention, it suffers from a poor performance in low light, limited field of view, and direct sunlight and is vulnerable to occlusions. Acoustic sensing can complement and even replace vision in many situations, and it also benefits from lower system cost and energy footprint, which is especially important for small form-factor aircraft. While novel acoustic technologies based on phased microphone arrays are making their way into the Internet of Things and home automation markets, their use in MAVs is currently impeded by the strong self-noise generated by the drone propulsion system. Consequently, existing commercial and research aerial platforms have advanced vision capabilities, yet no acoustics. This project targets to change this situation, endowing drones with "ears". The proposed research aims at the development of novel machine learning-based algorithms and real-time systems for acoustic-based autonomous mapping, localization, and interaction of MAVs. One of the key ideas of the proposal consists of actively controlling and shaping the aircraft self-noise for the benefit of the navigation and interaction tasks, instead of considering it a harmful nuisance. Our end goal is to demonstrate a flying proof-of-concept system which, to the best of our knowledge, will be the first of its kind. While the primary goal of the project is very specific, achieving it will require a considerable amount of scientific and methodological innovation in modelling, signal processing, and machine learning that we expect to have a significant impact on broad domains.

Mots-clés : acoustic imaging,inverse problem,intelligent systems,simultaneous localization and mapping
Projet ERC : ATG9_SOLVES_IT (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : The Francis Crick Institute — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2121055.0 €

Autophagy is a conserved, lysosomal-mediated pathway required for cell homeostasis and survival. It is controlled by the master regulators of energy (AMPK) and growth (TORC1) and mediated by the ATG (autophagy) proteins. Deregulation of autophagy is implicated in cancer, immunity, infection, aging and neurodegeneration. Autophagosomes form and expand using membranes from the secretory and endocytic pathways but how this occurs is not understood. ATG9, the only transmembrane ATG protein traffics through the cell in vesicles, and is essential for rapid initiation and expansion of the membranes which form the autophagosome. Crucially, how ATG9 functions is unknown. I will determine how ATG9 initiates the formation and expansion of the autophagosome by amino acid starvation through a molecular dissection of proteins resident in ATG9 vesicles which modulate the composition and property of the initiating membrane. I will employ high resolution light and electron microscopy to characterize the nucleation of the autophagosome, proximity-specific biotinylation and quantitative Mass Spectrometry to uncover the proteome required for the function of the ATG9, and optogenetic tools to acutely regulate signaling lipids. Lastly, with our tools and knowledge I will develop an in vitro reconstitution system to define at a molecular level how ATG9 vesicle proteins, membranes that interact with ATG9 vesicles, and other accessory ATG components nucleate and form an autophagosome. In vitro reconstitution of autophagosomes will be assayed biochemically, and by correlative light and cryo-EM and cryo-EM tomography, while functional reconstitution of autophagy will be tested by selective cargo recruitment. The development of a reconstituted system and identification proteins and lipids which are key components for autophagosome formation will provide a means to identify a new generation of targets for translational work leading to manipulation of autophagy for disease related therapies.

Mots-clés : autophagy,autophagosome formation,atg9,phagophore
Projet ERC : BONEPHAGY (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Telethon Foundation — Pays : Italie — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1586430.0 €

Autophagy is a fundamental cellular catabolic process deputed to the degradation and recycling of a variety of intracellular materials. Autophagy plays a significant role in multiple human physio-pathological processes and is now emerging as a critical regulator of skeletal development and homeostasis. We have discovered that during postnatal development in mice, the growth factor FGF18 induces autophagy in the chondrocyte cells of the growth plate to regulate the secretion of type II collagen, a major component of cartilaginous extracellular matrix. The FGF signaling pathways play crucial roles during skeletal development and maintenance and are deregulated in many skeletal disorders. Hence our findings may offer the unique opportunity to uncover new molecular mechanisms through which FGF pathways regulate skeletal development and maintenance and to identify new targets for the treatment of FGF-related skeletal disorders. In this grant application we propose to study the role played by the different FGF ligands and receptors on autophagy regulation and to investigate the physiological relevance of these findings in the context of skeletal growth, homeostasis and maintenance. We will also investigate the intracellular machinery that links FGF signalling pathways to the regulation of autophagy. In addition, we generated preliminary data showing an impairment of autophagy in chondrocyte models of Achondroplasia (ACH) and Thanathoporic dysplasia, two skeletal disorders caused by mutations in FGFR3. We propose to study the role of autophagy in the pathogenesis of FGFR3-related dwarfisms and explore the pharmacological modulation of autophagy as new therapeutic approach for achondroplasia. This application, which combines cell biology, mouse genetics and pharmacological approaches, has the potential to shed light on new mechanisms involved in organismal development and homeostasis, which could be targeted to treat bone and cartilage diseases.

Mots-clés : autophagy,lysosome,fibroblast growth factors,bone,cartilage
Projet ERC : LeukemiaEnviron (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Masaryk University — Pays : Rép. Tchèque — Rôle : PI
Acronyme de l'entité : MU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499990.0 €

B cell chronic lymphocytic leukemia (CLL) is the most frequent leukemia in adults. CLL cells are characterized by their universal dependency on pro-survival and pro-proliferative signals from immune niches. To achieve this they constantly re-circulate between blood and lymph nodes, which is inhibited by novel microenvironment-targeting therapies such as “BCR inhibitors”. We aim to reveal how the malignant B cells change the propensity of their signalling pathways in response to the different microenvironments such as peripheral blood vs lymph node to obtain the proliferative signals. This is of major relevance for CLL, but also transferable to the biology of some other B cell malignancies and/or normal B cells. We analyzed the “finger print” of microenvironmental interactions in many CLL samples at various times during the disease course or during therapy. The obtained data led us to hypothesize on the mechanisms of regulation of signalling propensity of two pathways that are responsible for proliferation and survival of CLL cells, namely B Cell Receptor (BCR) signalling and signals from T-cells mediated by CD40/IL4. In aim 1 we hypothesize that CD20 is one of the key proteins involved in CLL cell activation, and influences BCR and interleukin signalling (see figure). This has important therapeutic implication since CD20 is used as a therapeutic target for 20 years (rituximab), but its function in CLL/normal B cells is unknown. In aim 2 we hypothesize that miR-29 acts a key regulator of T-cell signalling from CD40 and down-stream NFkB activation (see figure). This represents the first example of miRNAs‘ role in the propensity of T-cell interaction, and could be also utilized therapeutically. In aim 3 we will integrate our data on microenvironmental signaling (aim 1+2) and develop a first mouse model for PDX that would allow stable engraftment of primary CLL cells. Currently, CLL is non-transplantable to any animal model which complicates studies of its biology.

Mots-clés : chronic lymphocytic leukemia,b cells,b cell receptor signalling,microrna,mirna,therapy,microenvironment
Projet ERC : TEMUBLYM (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Spanish National Research Council — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 1866046.0 €

B cells are one of the main players of immunity, responsible for the production of immunoglobulins (Igs). In 2011, I was granted an ERC Starting grant to undertake the phenotypical and functional characterization of teleost B lymphocytes based on the hypothesis that they do not behave as mammalian B2 cells (conventional B cells) but closely resemble mammalian innate B1 lymphocytes involved in extrafollicular T-independent (TI) responses. Since then, my laboratory has gathered considerable evidences that strengthen this hypothesis. These studies were mostly carried out in central lymphoid compartments, but did not address how teleost B1-like cells regulate the delicate balance between immunity and tolerance at mucosal interfaces, in species lacking follicular structures. In this new project, I want to pursue my studies on B lymphocyte functionality, focusing on how teleost mucosal B cells are regulated, still under the assumption that fish B lymphocytes resemble better a B1 model. We will study how fish B cells differentiate to antibody secreting cells (ASCs) and establish extrafollicular long-term memory, taking into account novel results in mammals that have challenged traditional paradigms and revealed that long-term immunological memory can be established through TI IgM B1-like responses. Furthermore, we will also study the role of IgD in the gills, as previous studies from my group suggest that this Ig plays a key role in the regulation of immunity in this specific mucosa, as it seems to do in humans in areas such as the upper respiratory tract. Addressing how fish B cells mount a protective mucosal immune response in the absence of T cell help from organized follicles could provide new mechanistic insights into IgM and IgD responses emerging in humans. From a practical view, our work will contribute to understand why satisfactory mucosal vaccination is still an unreached goal for most diseases in both mammals and fish, despite their strong demand.

Mots-clés : teleost fish,b lymphocytes,mucosal immunity,antibody secreting cells  ascs,intestine,gills
Projet ERC : CAMERA (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : University of Lausanne — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UNIL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1438018.37 €

BACKGROUND Ancient DNA research has recently entered the genomics era. Performing “ancient population genomics” is now technically possible. Utilizing the temporal aspect of this new data, we can address fundamental evolutionary questions such as the amount of selection acting on the genome or the mode and tempo of the colonization of the world. AIMS The overall goal of the proposed research is to (i) generate and analyse data to answer two long standing questions in human evolution: understanding the molecular basis of human adaptation to high altitude and investigating the timing of the Polynesian-South American contact, (ii) develop statistical approaches that combine ancient and modern genetic data to estimate the timing and the intensity of a selective sweep and an admixture event. METHODOLOGY Application: We will collect, date and DNA sequence human remains. Combining the ancient genetic data, 14C dates with existing modern genomic data will allow us to increase the resolution as to the timing of the adaptive and the admixture event, respectively, while generating unique datasets. Theory: We will build on existing methods based on one-locus classical population genetic models to develop tools to analyse whole genome time serial data. RELEVANCE Ecological: The results will address the fundamental question of how much of the human genome is undergoing selection, better characterize one of the textbook examples of adaptation in humans and contribute to our understanding of the peopling of the Americas. Medical: We will gain insights into the fundamental stress physiology experienced at high altitude and therefore into altitude-related illnesses. Methodological: The methods developed in this project will not only benefit the growing field of ancient genomics but also other fields where data is collected in a temporal manner, such as experimental evolution and epidemiology

Mots-clés : ancient dna
Projet ERC : BACKWARD (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
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 : 2499276.0 €

BACKWARD will address major unsettled debates about African and Asian extinct hominid phylogeny, by developing and deploying a new generation of palaeoproteomic workflows, relying on the most advanced mass spectrometry and bioinformatic solutions currently available. Ancient DNA (aDNA) sequencing revolutionised our knowledge on evolution, migration and admixture of archaic and anatomically modern humans. However, no hominid aDNA older than ~0.4 million years has been retrieved yet. Ancient proteins instead survive much longer than aDNA, enabling molecular-based phylogeny beyond the limits of aDNA degradation. Recently, mass spectrometry (MS)-based ancient protein sequencing, i.e. palaeoproteomics, convincingly demonstrated its transformative value, enabling molecular-based evolutionary reconstructions for species that went extinct millions of years ago. BACKWARD will use palaeoproteomics to address: (i) the phylogenetic relationships among South African early hominins, and (ii) the hominid palaeobiodiversity in Southeast Asia; two topics debated for generations, and further complicated by recent finds. This knowledge will also provide the evolutionary scaffolding needed to correctly identify and correlate the series of processes that defined human brain expansion and reorganization. BACKWARD will also screen large sets of morphologically non-informative isolated fossil fragments of bones and teeth, to identify the species and sex of the organism from which they originated. Some of these solutions will be commercially re-purposed to deliver superior performance in public and private analytic laboratories for diagnostics in forensic medicine, and in the food or pharmaceutical industry. As a key BACKWARD feature, the unique contribution provided by each participating institution will be integrated in a strong partnership to transform palaeoanthropology, palaeontology, palaeoecology and archaeology once again, as aDNA did over the last twenty years.

Mots-clés : early south african hominins,east asian extinct hominids,palaeoproteomics,ancient proteins,mass spectrometry,molecular phylogeny
Projet ERC : BEHAVFRICTIONS (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : Czech Academy of Sciences — Pays : Rép. Tchèque — Rôle : PI
Acronyme de l'entité : AVČR;CAS
Type d'entité : Recherche
Financement ERC de l'entité : 871302.5 €

BEHAVFRICTIONS will use novel models focussing on information-processing frictions to explain choice patterns described in behavioral economics and psychology. The proposed research will provide microfoundations that are essential for (i) identification of stable preferences, (ii) counterfactual predictions, and (iii) normative conclusions. (i) Agents who face information-processing costs must trade the precision of choice against information costs. Their behavior thus reflects both their stable preferences and the context-dependent procedures that manage their errors stemming from imperfect information processing. In the absence of micro-founded models, the two drivers of the behavior are difficult to disentangle for outside observers. In some pillars of the proposal, the agents follow choice rules that closely resemble logit rules used in structural estimation. This will allow me to reinterpret the structural estimation fits to choice data and to make a distinction between the stable preferences and frictions. (ii) Such a distinction is important in counterfactual policy analysis because the second-best decision procedures that manage the errors in choice are affected by the analysed policy. Incorporation of the information-processing frictions into existing empirical methods will improve our ability to predict effects of the policies. (iii) My preliminary results suggest that when an agent is prone to committing errors, biases--such as overconfidence, confirmatory bias, or perception biases known from prospect theory--arise under second-best strategies. By providing the link between the agent's environment and the second-best distribution of the perception errors, my models will delineate environments in which these biases shield the agents from the most costly mistakes from environments in which the biases turn into maladaptations. The distinction will inform the normative debate on debiasing.

Mots-clés : stochastic choice,information processing frictions,error management,microfoundations of behavioural economics
Projet ERC : BrainModes (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Charité - Universitätsmedizin Berlin — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1870588.0 €

Background. We have detailed maps of brain structure and function, yet are lacking understanding of how the highly connected units interact and give rise to mental processes. The Virtual Brain (TVB), a whole brain simulation framework, aims to bridge that gap. Yet it is still developing. We are proposing here breakthrough advances that reveal mechanisms of brain function and foster collaboration between research groups. Vision. Clinical applications that simulate individual patient brains and predict trajectories of recovery or decline or test therapies to select the best one for that person. Goal. Using biologically realistic brain models and multimodal functional and structural imaging data to elucidate control mechanisms of the human brain in aging. A database collects key data and allows identifying most generic models and mechanisms below the spatial and temporal resolution of non-invasive imaging techniques taking into account the complex interaction in the brain that without a model would be impossible to keep track of. Objectives. 1) Parameter optimization for large parameter space search and a library of dynamical regimes linking dynamical regimes and underlying mechanisms to biological (cognitive) age. 2) Identifying the role of intrinsic plasticity for network reconfigurations in the resting state and its age dependency. 3) Model based identification of task related plasticity mechanisms and their functional consequences for network reconfigurations in coordination learning in aging. 4) An interactive tool that provides access to the dynamical regimes library and makes pre-computed simulations easily accessible allowing researchers to benefit and learn from existing work. Impact. Understanding development, aging and brain disorders from the perspective of disruption of information processing architectures provides an opportunity for new interventions that re-establish control in brain pathology hence posing a breakthrough in the health and biotech sector.