Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : DiurnalHealth (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Leiden University Medical Center — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : LUMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2166755.63 €

Due to a significant increase in the use of artificial light in our 24h economy, the biological clocks of all living organisms, including humans, are severely disrupted. Many severe health disorders are consequences of clock disruption such as diabetes, sleep/mood disorders, cardiovascular disease, and immune dysfunction. The central timekeeper in mammals is the suprachiasmatic nucleus (SCN), and the mechanisms by which light disrupts integrity of the SCN has been well investigated in nocturnal species. In contrast, mechanisms of clock disruption in humans and other diurnal (day-active) species remain poorly defined. I have evidence that the mechanisms that drive SCN function are fundamentally different between nocturnal species and diurnal species. This defines my aim to restore proper clock function in diurnal species, including humans. To test this, in Objective 1 we will identify similarities and differences between nocturnal and diurnal clocks with respect to their i) response to light, ii) neuronal synchronization, iii) output, and iv) response to physical activity. Based on these findings, in Objective 2 we will develop novel strategies to manipulate and restore clock function in diurnal species. These objectives will be achieved using novel, state-of-the-art chronobiology methods including in vivo electrophysiology and Ca2+ and bioluminescence reporters—all in freely behaving day-active animals, as well as in slice preparations containing the SCN. For studies on the human SCN we record with 7-Tesla fMRI. This proposal will help establish a new basis for chronobiology with respect to the most suitable models for studying translational applications. The results will yield immediate benefits in terms of manipulating biological clock function among vulnerable populations in modern society, particularly the elderly, patients in intensive care, and shift workers.

Mots-clés : circadian,in vivo electrophysiology,neuronal network,neurophysiology,light input,light pollution,seasonal rhythms,exercise,health,synchronization,sleep,behaviour,plasticity
Projet ERC : ImageToSim (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Technical University of Darmstadt — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1040821.09 €

Due to the intricate process of transferring diagnostic imaging data into patient-specific models, simulation workflows involving complex physiological geometries largely rely on the manual intervention of specially trained analysts. This constitutes a significant roadblock for a wider adoption of predictive simulation in clinical practice, as the associated cost and response times are incompatible with tight budgets and urgent decision-making. Therefore, a new generation of imaging-through-analysis tools is needed that can be run autonomously in hospitals and medical clinics. The overarching goal of ImageToSim is to make substantial progress towards automation by casting image processing, geometry segmentation and physiology-based simulation into a unifying finite element framework that will overcome the dependence of state-of-the-art procedures on manual intervention. In this context, ImageToSim will fill fundamental technology gaps by developing a series of novel comprehensive variational multiscale methodologies that address robust active contour segmentation, upscaling of voxel-scale parameters, transition of micro- to macro-scale failure and flow through vascular networks of largely varying length scales. Focusing on osteoporotic bone fracture and liver perfusion, ImageToSim will integrate the newly developed techniques into an imaging-through-analysis prototype that will come significantly closer to automated operation than any existing framework. Tested and validated in collaboration with clinicians, it will showcase pathways to new simulation-based clinical protocols in osteoporosis prevention and liver surgery planning. Beyond its technical scope, ImageToSim will help establish a new paradigm for patient-specific simulation research that emphasizes full automation as a key objective, accelerating the much-needed transformation of healthcare from reactive and hospital-centered to preventive, proactive, evidence-based, and person-centered.

Mots-clés : finite element method,computational solid mechanics,computational fluid mechanics,multiscale analysis,bone fracture,liver perfusion,variational and pde based image processing
Projet ERC : DUNES (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : University of Lisbon — Pays : Portugal — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1062330.0 €

Dunes are now protected environments, being top priority for coastal managers, because of their important role as coastal defences. But, it was not like that in the past. For centuries dunes were considered unproductive and dangerous. The sand blown by the wind was taken inland, invading fields, silting rivers and destroying villages. In the eighteenth century, a strategy was developed to fight against the dunes: trapping them with trees, with the double purpose of preventing the destruction of arable land and increasing their economic value converting them into forest areas. Different governments, in different countries supported the immobilization of the shifting sands. The strategy, developed in Europe, was taken to other places in the world. These works caused profound changes in vast coastal areas transforming arid landscapes of sandy dunes into green tree forests. This project aims to explore human-environment relations in coastal areas worldwide, since the eighteenth century until today, through the study of dunes as hybrid landscapes. Based on selected case-studies and comparative approaches, the project will focus on the origins, reasons and means of dunes afforestation; the impacts of the creation of new landscapes to local communities and ecosystems; and the present situation of dunes as coastal defences and rehabilitated environments. The final purpose is to produce an innovative global history of coastal dunes, combining knowledges from both Humanities and Social Sciences and Physical and Life Sciences, which has never been done. Supported by an interdisciplinary team, this research will result in new developments in the field of the Environmental History studies; provide relevant knowledge considering the need of efficient management solutions to adapt to the expected mean sea level rise; and stimulate environmental citizenship by disseminating the idea that the future of the world coasts depends on today’s actions.

Mots-clés : environmental history,coastal zones,governance,environmental citizenship
Projet ERC : CohesinMolMech (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Research Institute of Molecular Pathology — Pays : Autriche — Rôle : PI
Acronyme de l'entité : IMP
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 2500000.0 €

During S-phase newly synthesized “sister” DNA molecules become physically connected. This sister chromatid cohesion resists the pulling forces of the mitotic spindle and thereby enables the bi-orientation and subsequent symmetrical segregation of chromosomes. Cohesion is mediated by ring-shaped cohesin complexes, which are thought to entrap sister DNA molecules topologically. In mammalian cells, cohesin is loaded onto DNA at the end of mitosis by the Scc2-Scc4 complex, becomes acetylated during S-phase, and is stably “locked” on DNA during S- and G2-phase by sororin. Sororin stabilizes cohesin on DNA by inhibiting Wapl, which can otherwise release cohesin from DNA again. In addition to mediating cohesion, cohesin also has important roles in organizing higher-order chromatin structures and in gene regulation. Cohesin performs the latter functions in both proliferating and post-mitotic cells and mediates at least some of these together with the sequence-specific DNA-binding protein CTCF, which co-localizes with cohesin at many genomic sites. Although cohesin and CTCF perform essential functions in mammalian cells, it is poorly understood how cohesin is loaded onto DNA by Scc2-Scc4, how cohesin is positioned in the genome, how cohesin is released from DNA again by Wapl, and how Wapl is inhibited by sororin. Likewise, it is not known how cohesin establishes cohesion during DNA replication and how cohesin cooperates with CTCF to organize chromatin structure. Here we propose to address these questions by combining biochemical reconstitution, single-molecule TIRF microscopy, genetic and cell biological approaches. We expect that the results of these studies will advance our understanding of cell division, chromatin structure and gene regulation, and may also provide insight into the etiology of disorders that are caused by cohesin dysfunction, such as Down syndrome and “cohesinopathies” or cancers, in which cohesin mutations have been found to occur frequently.

Mots-clés : cohesin,ctcf,higher order chromatin structure,mammalian cells,protein biochemistry,sister chromatid cohesion,tirf microscopy,xenopus egg extracts
Projet ERC : EpiCrest2Reg (Horizon 2020, appel 2018, Synergy grants)
Entité participante : Friedrich Miescher Institute — Pays : Suisse — Rôle : CO-PI
Acronyme de l'entité : FMI
Type d'entité : Recherche
Financement ERC de l'entité : 2670000.0 €

During craniofacial development, Cranial Neural Crest Cells (CNCCs) maintain broad plasticity and patterning competence until they make appropriate cartilage and bone structures in response to local cues. We found that CNCC embryonic plasticity involves a specific epigenetic chromatin signature that maintains genes, including Hox genes, in a transcriptionally silent but poised state, so that they can be readily switched to an active state in response to position-specific environmental signals. Are there CNCC-derived subpopulations in the adult face cartilage with similar broad plasticity properties that could be used as progenitor source in regenerative medicine? We have shown that Hox-negative adult human CNCC-derived Nasal Chondrocytes (NCs) have cartilage regenerative capacity and plasticity to adapt to heterotopic sites larger than other cell sources, and demonstrated their potential clinical use for articular cartilage repair. However, lack of understanding of the involved molecular mechanisms limits the broader utilization of adult NCs for the regeneration of other cartilage types, e.g. the intervertebral disc (IVD). This proposal will establish fundamental understanding of the biological processes responsible for the plasticity of adult human NCs and offer a paradigm example of scientific and clinical synergies bridging developmental (epi)genetics and regenerative medicine. We will: • Establish whether Hox-negative adult NCs and embryonic CNCCs share similar transcriptomes, epigenomes and 3D chromatin architectures using single cell RNA-seq, ChIP-seq and capture HiC-seq assays. • Assess whether NCs can epigenetically and transcriptionally adapt to the Hox-positive IVD environment, using co-culture and bioreactor-based organ culture models, and investigate the underlying molecular mechanisms. • Verify the capacity of adult NCs to repair degenerated IVD cartilage. • Use human autologous NCs for repair of IVD degeneration in a phase I clinical trial.

Mots-clés : cranial neural crest cells,epigenetic and transcriptional regulation,craniofacial development,nasal chondroprogenitor cells,mouse,cartilage regeneration in humans,hox genes
Projet ERC : MUSIX (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Institut national de recherche pour l'agriculture, l'alimentation et l'environnement — Pays : France — Rôle : PI
Acronyme de l'entité : Inrae
Type d'entité : Recherche
Financement ERC de l'entité : 2176170.0 €

During development, living organisms change shape and thus also change structure. The resulting pattern of force controls cell behavior and thus development. However, the molecular mechanoperception mechanisms involved are only partially understood and how organs integrate local and global patterns of forces is another open question. Plants are ideal systems to study the multicellular implications of mechanotransduction in development because their mechanics is mainly mediated by the cell wall and cells do not move. In past work, we showed that microtubules align with maximal tensile stress direction in planta, thereby guiding the deposition of stiff cellulose microfibrils in cell walls, thus altering organ shape in a feedback loop. Based on our preliminary data, we will test the hypothesis that microtubules are their own mechanosensors, and that wall sensing interferes with this response to account for cell geometry or intercellular cues. The main technical breakthrough behind MUSIX is the introduction of a novel, high-throughput, single cell system in which the wall is replaced by an artificial well, enabling its mechanics and chemistry to be modulated. This simpler approach will allow us to dissect the contribution of wall components in mechanosensing in the absence of interfering global molecular cues. We will then integrate these biophysical mechanisms in multicellular development. Using natural and artificial mosaics (Cre-Lox system) in plant organoids and real organs, we will explore how the autonomous microtubule response to stress integrates mechanical conflicts between adjacent cells in tissues through wall sensing. This work has important implications beyond plant science, including cell signaling (how cells perceive their environment), developmental proprioception (how organs perceive and monitor their own shape and growth), compensation (how organs manage growth-derived mechanical conflicts) and robustness (how tissues manage growth fluctuations).

Mots-clés : biophysics,computational modeling,mechanotransduction,proprioception,arabidopsis,microtubules,cell wall
Projet ERC : SymPore (Horizon 2020, appel 2020, Synergy grants)
Entité participante : Heinrich Heine University Düsseldorf — Pays : Allemagne — Rôle : CO-PI
Acronyme de l'entité : HHU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 5470125.0 €

During evolution of multicellularity, cells differentiated to become specialized and interdependent. Multicellular organisms invented channels for nutrient exchange and communication between cells. Plants uniquely developed plasmodesmata, complex cell-cell connections traversing the cell wall. Roles ascribed to plasmodesmata include selective transport of signals, ions, metabolites, RNAs and proteins. Due to technical hurdles, composition, structure and regulation of plasmodesmatal conductance remain enigmatic. Genetic approaches to study plasmodesmata were hampered by lethality or redundancy. Novel technologies now set the stage for resolving roles of plasmodesmata in transport and signaling in an interdisciplinary approach. We will use proximity labeling proteomics to obtain plasmodesmatal composition, and PAINT and cryo electron tomography (cryoET) for near atomic structures. Models of plasmodesmata will be built from bottom up and top down approaches and combined with quantitative assessment of plasmodesmatal activity. Novel biosensor approaches together with knock down by genome editing will permit quantitation of transport of the diverse cargo. Single cell sequencing helps fine-tuning mutant selection and targeting of subtypes. Four labs will join forces: highly recognized experts in biophysics and cryoET (WB), advanced imaging and developmental signaling (RS), high-end proteomics and lipidomics (WS), and interactomics, transporters and cutting-edge biosensor technology (WF). We will iteratively address: (1) systematic quantitative identification of components, (2) their localization and dynamics, (3) structures and molecular building blocks of diverse plasmodesmatal types, and (4) transport and signaling mechanisms. We expect breakthrough discoveries and completely new understanding of plasmodesmatal function and evolution. Since plasmodesmata play key roles in nutrient allocation and virus spread, we lay the basis for novel biotech solutions in agriculture.

Mots-clés : cryo electron tomography,protein interactions,imaging,microscopy,mass spectrometry,transport,modeling,biosensors,plant,moss,arabidopsis,plasmodesmata,genome editing,signaling,cytoplasmic bridges,pit plugs,development,physiology,evolution
Projet ERC : SymPore (Horizon 2020, appel 2020, Synergy grants)
Entité participante : University of Hohenheim — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2640375.0 €

During evolution of multicellularity, cells differentiated to become specialized and interdependent. Multicellular organisms invented channels for nutrient exchange and communication between cells. Plants uniquely developed plasmodesmata, complex cell-cell connections traversing the cell wall. Roles ascribed to plasmodesmata include selective transport of signals, ions, metabolites, RNAs and proteins. Due to technical hurdles, composition, structure and regulation of plasmodesmatal conductance remain enigmatic. Genetic approaches to study plasmodesmata were hampered by lethality or redundancy. Novel technologies now set the stage for resolving roles of plasmodesmata in transport and signaling in an interdisciplinary approach. We will use proximity labeling proteomics to obtain plasmodesmatal composition, and PAINT and cryo electron tomography (cryoET) for near atomic structures. Models of plasmodesmata will be built from bottom up and top down approaches and combined with quantitative assessment of plasmodesmatal activity. Novel biosensor approaches together with knock down by genome editing will permit quantitation of transport of the diverse cargo. Single cell sequencing helps fine-tuning mutant selection and targeting of subtypes. Four labs will join forces: highly recognized experts in biophysics and cryoET (WB), advanced imaging and developmental signaling (RS), high-end proteomics and lipidomics (WS), and interactomics, transporters and cutting-edge biosensor technology (WF). We will iteratively address: (1) systematic quantitative identification of components, (2) their localization and dynamics, (3) structures and molecular building blocks of diverse plasmodesmatal types, and (4) transport and signaling mechanisms. We expect breakthrough discoveries and completely new understanding of plasmodesmatal function and evolution. Since plasmodesmata play key roles in nutrient allocation and virus spread, we lay the basis for novel biotech solutions in agriculture.

Mots-clés : cryo electron tomography,protein interactions,imaging,microscopy,mass spectrometry,transport,modeling,biosensors,plant,moss,arabidopsis,plasmodesmata,genome editing,signaling,cytoplasmic bridges,pit plugs,development,physiology,evolution
Projet ERC : INTEGRATE (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
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 : 2499714.0 €

During evolution the brain has selected glucose as a main source of metabolic energy. This has imposed homeostatic and behavioral constraints. First, the glycemic levels must be maintained at a minimum of ~5 mM to ensure constant energy supply to the brain. Second, a high reward value has to be attributed to glucose-containing foods to increase the motivation to obtain them. These homeostatic and hedonic regulations depend on glucose sensing cells and neuronal circuits in the central nervous system. These cells and circuits regulate the activity of the sympathetic and parasympathetic nerves, which control the function of peripheral organs (liver, fat, muscles) and the secretion of glucagon and insulin by pancreatic islet cells. They also attribute a reward value to glucose-containing foods to control food-seeking behavior, a process that involves the mesolimbic dopaminergic system. Here, we will focus on three interrelated aims: 1. Identify the physiological role of glucose sensing neurons of the ventromedial hypothalamic nucleus (VMN, a key feeding and glucoregulatory center) in glucose homeostasis and food preference; identify their cellular diversity and their molecular make-up; and characterize their deregulations in metabolic diseases. 2. Characterize the molecular physiology of glucose sensing neurons of the paraventricular thalamus, which modulate the activity of the mesolimbic dopaminergic system to control motivated sucrose-seeking behavior; determine their control by other interoceptive signals, including from glucose sensing cells of the VMN. 3. Establish new molecular approaches to characterize, at the molecular and functional levels, the impact of early postnatal nutrition on the development and function of central glucose sensing cells in the control of adult animal physiology. These studies will open-up new perspectives in the understanding of homeostatic and hedonic regulatory pathways, which preserve metabolic health over a lifetime.