Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : spim4You (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 148613.0 €

Biological research heavily relies on visualization of biological samples by microscopy. In recent years light-sheet microscopy has emerged as a paradigm shifting technique. Only with light sheet microscopy it is for instance possible to follow every cell in a living system throughout development, to monitor brain activity of a live animal or to study cancer cells in their native three dimensional environment within an organism. Thus, light sheet microscopy has the potential to revolutionize biological research and in the near future every research establishment will have a light sheet microscope. During the Hourglass ERC grant, my laboratory developed two widely used open access solutions for light sheet microscopy: 1.) OpenSPIM, a modular open hardware platform that enables anyone to construct and operate a simple light sheet microscope and 2.) a powerful library of open source software solutions to process and analyze lights sheet microscopy data. Together, these tools form a powerful foundation for exploiting the spectacular benefits of light sheet microscopy for research. The problem is however that in order to use light sheet microscopy a formidable set of expertise spanning physics, engineering, computer science and biology is required and only very few research laboratories have this level of interdisciplinary skills. The idea of our Proof of Concept proposal is to leverage the unique know-how of my laboratory generated during the ERC funding period and establish a company that will offer biology researchers assistance with all aspects of light sheet microcopy from hardware, through operation to computational data analysis. We plan to establish an expandable light sheet microscopy service - spim4You – at a time when this powerful technique enters the research mainstream and was named Method of the Year by Nature Methods.

Mots-clés : custom microscopy,imaging analysis software,imaging hardware,microscopy service,software service,education microscopes,personalized microscopy,microscopes,training
Projet ERC : AHH-OMICS (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 240207.5 €

Biological systems rely on an influx of energy to build and maintain complex spatio-temporal structures. A striking example of this is the self-organisation of cells into tissues, which relies on an interplay of molecular programs and tissue-level feedback. The mechanistic basis underlying these processes is poorly understood. The recent advent of single-cell sequencing technologies for the first time gives the opportunity to probe these processes with unprecedented molecular resolution in vivo. Biological function, however, relies on collective processes on the cellular scale which emerge from many interactions on the microscopic scale. But what can we learn about such collective processes from detailed empirical information on the molecular scale? Concepts from non-equilibrium statistical physics provide a powerful framework to understand collective processes underlying the self-organisation of cells. In the proposed research endeavour, we will combine the possibilities of novel single-cell technologies with methods from non-equilibrium statistical physics to understand collective processes regulating cellular behaviour. Using this conceptually new approach, we will 1) unveil collective epigenetic processes during differentiation, reprogramming and ageing, 2) determine how the interplay between different layers of regulation leads to the emergence of mesoscopic spatio-temporal structures in vivo, and 3) understand universal fluctuations in gene expression to unveil mechanistic principles of cellular decisions. Our theoretical work will be challenged by single-cell sequencing experiments performed by our collaborators. We will overcome important conceptual limitations in an emerging technology in biology and pioneer the application of methods from non-equilibrium statistical physics to single-cell genomics. At the same time, we take an interdisciplinary approach to tackle questions at the frontier of non-equilibrium physics.

Mots-clés : single cell genomics,epigenetics,dna methylation,field theory,non equilibrium physics,stem cell biology
Projet ERC : BIOVIB (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : Forschungsverbund Berlin — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : FVB
Type d'entité : Recherche
Financement ERC de l'entité : 2330492.5 €

Biomolecules exist in an aqueous environment of dipolar water molecules and solvated ions. Their structure and biological function are strongly influenced by electric interactions with the fluctuating water shell and ion atmosphere. Understanding such interactions at the molecular level is a major scientific challenge; presently, their strengths, spatial range and interplay with other non-covalent interactions are barely known. Going far beyond existing methods, this project introduces the new paradigm of a direct time-resolved mapping of molecular electric forces on sub-nanometer length scales and at the genuine terahertz (THz) fluctuation frequencies. Vibrational excitations of biomolecules at the interface to the water shell act as sensitive noninvasive probes of charge dynamics and local electric fields. The new method of time resolved vibrational Stark shift spectroscopy with THz external fields calibrates vibrational frequencies as a function of absolute field strength and separates instantaneous from retarded environment fields. Based on this knowledge, multidimensional vibrational spectroscopy gives quantitative insight in the biomolecular response to electric fields, discerning contributions from water and ions in a site-specific way. The experiments and theoretical analysis focus on single- and double-stranded RNA and DNA structures at different hydration levels and with ion atmospheres of controlled composition, structurally characterized by x-ray scattering. As a ground-breaking open problem, the role of magnesium and other ions in RNA structure definition and folding will be addressed by following RNA folding processes with vibrational probes up to milliseconds. The impact of site-bound versus outer ions will be dynamically separated to unravel mechanisms stabilizing secondary and tertiary RNA structures. Beyond RNA research, the present approach holds strong potential for fundamental insight in transmembrane ion channels and channel rhodopsins.

Mots-clés : hydrated biomolecules,water shell,non covalent interactions,electric forces,ion atmosphere,ultrafast structural dynamics,femtosecond vibrational spectroscopy,terahertz methods
Projet ERC : CuRE (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
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 : 2428492.0 €

Biotechnological therapies for patients with myocardial infarction and heart failure are urgently needed, in light of the breadth of these diseases and a lack of curative treatments. CuRE is an ambitious project aimed at identifying novel factors (cytokines, growth factors, microRNAs) that promote cardiomyocyte proliferation and can thus be transformed into innovative therapeutics to stimulate cardiac regeneration. The Project leads from two concepts: first, that cardiac regeneration can be obtained by stimulating the endogenous capacity of cardiomyocytes to proliferate, second that effective biotherapeutics might be identified through systematic screenings both in vivo and ex vivo. In the mouse, CuRE will take advantage of two unique arrayed libraries cloned in adeno-associated virus (AAV) vectors, one corresponding to the secretome (1200 factors) and the other to the miRNAome (800 pri-miRNA genes). Both libraries will be functionally screened in mice to search for factors that enhance cardiac regeneration. This in vivo selection approach will be complemented by a series of high throughput screenings on primary cardiomyocytes ex vivo, aimed at systematically assessing the involvement of all components of the ubiquitin/proteasome pathway, the cytoskeleton and the sarcomere on cell proliferation. Cytokines and miRNAs can both be developed to become therapeutic molecules, in the form of recombinant proteins and synthetic nucleic acids, respectively. Therefore, a key aim of CuRE will be to establish procedures for their production and administration in vivo, and to assess their efficacy in both small and large animal models of myocardial damage. In addition to this translational goal, the project will entail the successful achievement of several intermediate objectives, each of which possesses intrinsic validity in terms of basic discovery and is thus expected to extend technology and knowledge in the cardiovascular field beyond state-of-the art.
Projet ERC : SOL (Horizon 2020, appel 2020, Synergy grants)
Entité participante : Humboldt-Universität zu Berlin — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : HU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2346875.0 €

Bistable rhodopsins are naturally photosensitive G-protein coupled receptors (GPCRs) that can be toggled between stable ON and OFF states using light. They are responsible for photosensitivity and vision across animals (including humans), and a potential source of powerful optogenetic tools enabling bidirectional control of influential intracellular signalling cascades across all body systems using light. Lack of understanding of structure-function relationships for these proteins curtails understanding of their biology and their engineering for optogenetic purposes. PI Kleinlogel first demonstrated that chimeras between bistable rhodopsin and ligand GPRCs can be functionally active and provoke a strong physiological response when expressed in vivo. PI Schertler has extensive experience in the structural analysis of rhodopsins and has successfully solved the first structure of a recombinantly expressed bistable rhodopsin. PI Hegemann has longstanding experience in the spectroscopic characterisation and engineering of photoreceptor proteins and is one of the founding fathers of optogenetics. PI Lucas pioneered cellular systems suitable for analysing spectral properties and G protein selectivity and had a leading role in elucidating the physiological role of the bistable rhodopsin melanopsin. Together, the team aims to understand how structural features of these influential photoreceptors define their bistability, bichromicity, kinetics, and G-protein selectivity (Objective 1). We will exploit this knowledge for rational engineering towards colour tuning and G protein selectivity for optogenetic tools (Objective 2) and to probe physiological functions (Objective 3). The result will be a decisive step towards a general theory of structure-function relationship in photoreceptors and will produce a new generation of powerful optogenetic tools enabling defined GPCR signalling activities in any cell type.

Mots-clés : structure based protein engineering,single particle cryo electron microscopy,time resolved serial room temperature crystallography,optogenetics,retinal proteins,g protein coupled receptor signalling,cellular functional protein analysis,photobiology,photochemistry,electrophysiology,tissue specific in vivo expression
Projet ERC : SOL (Horizon 2020, appel 2020, Synergy grants)
Entité participante : University of Freiburg — Pays : Allemagne — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 212500.0 €

Bistable rhodopsins are naturally photosensitive G-protein coupled receptors (GPCRs) that can be toggled between stable ON and OFF states using light. They are responsible for photosensitivity and vision across animals (including humans), and a potential source of powerful optogenetic tools enabling bidirectional control of influential intracellular signalling cascades across all body systems using light. Lack of understanding of structure-function relationships for these proteins curtails understanding of their biology and their engineering for optogenetic purposes. PI Kleinlogel first demonstrated that chimeras between bistable rhodopsin and ligand GPRCs can be functionally active and provoke a strong physiological response when expressed in vivo. PI Schertler has extensive experience in the structural analysis of rhodopsins and has successfully solved the first structure of a recombinantly expressed bistable rhodopsin. PI Hegemann has longstanding experience in the spectroscopic characterisation and engineering of photoreceptor proteins and is one of the founding fathers of optogenetics. PI Lucas pioneered cellular systems suitable for analysing spectral properties and G protein selectivity and had a leading role in elucidating the physiological role of the bistable rhodopsin melanopsin. Together, the team aims to understand how structural features of these influential photoreceptors define their bistability, bichromicity, kinetics, and G-protein selectivity (Objective 1). We will exploit this knowledge for rational engineering towards colour tuning and G protein selectivity for optogenetic tools (Objective 2) and to probe physiological functions (Objective 3). The result will be a decisive step towards a general theory of structure-function relationship in photoreceptors and will produce a new generation of powerful optogenetic tools enabling defined GPCR signalling activities in any cell type.

Mots-clés : structure based protein engineering,single particle cryo electron microscopy,time resolved serial room temperature crystallography,optogenetics,retinal proteins,g protein coupled receptor signalling,cellular functional protein analysis,photobiology,photochemistry,electrophysiology,tissue specific in vivo expression
Projet ERC : SOL (Horizon 2020, appel 2020, Synergy grants)
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : CO-PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Recherche
Financement ERC de l'entité : 2552015.0 €

Bistable rhodopsins are naturally photosensitive G-protein coupled receptors (GPCRs) that can be toggled between stable ON and OFF states using light. They are responsible for photosensitivity and vision across animals (including humans), and a potential source of powerful optogenetic tools enabling bidirectional control of influential intracellular signalling cascades across all body systems using light. Lack of understanding of structure-function relationships for these proteins curtails understanding of their biology and their engineering for optogenetic purposes. PI Kleinlogel first demonstrated that chimeras between bistable rhodopsin and ligand GPRCs can be functionally active and provoke a strong physiological response when expressed in vivo. PI Schertler has extensive experience in the structural analysis of rhodopsins and has successfully solved the first structure of a recombinantly expressed bistable rhodopsin. PI Hegemann has longstanding experience in the spectroscopic characterisation and engineering of photoreceptor proteins and is one of the founding fathers of optogenetics. PI Lucas pioneered cellular systems suitable for analysing spectral properties and G protein selectivity and had a leading role in elucidating the physiological role of the bistable rhodopsin melanopsin. Together, the team aims to understand how structural features of these influential photoreceptors define their bistability, bichromicity, kinetics, and G-protein selectivity (Objective 1). We will exploit this knowledge for rational engineering towards colour tuning and G protein selectivity for optogenetic tools (Objective 2) and to probe physiological functions (Objective 3). The result will be a decisive step towards a general theory of structure-function relationship in photoreceptors and will produce a new generation of powerful optogenetic tools enabling defined GPCR signalling activities in any cell type.

Mots-clés : structure based protein engineering,single particle cryo electron microscopy,time resolved serial room temperature crystallography,optogenetics,retinal proteins,g protein coupled receptor signalling,cellular functional protein analysis,photobiology,photochemistry,electrophysiology,tissue specific in vivo expression
Projet ERC : SOL (Horizon 2020, appel 2020, Synergy grants)
Entité participante : University of Manchester — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2859998.75 €

Bistable rhodopsins are naturally photosensitive G-protein coupled receptors (GPCRs) that can be toggled between stable ON and OFF states using light. They are responsible for photosensitivity and vision across animals (including humans), and a potential source of powerful optogenetic tools enabling bidirectional control of influential intracellular signalling cascades across all body systems using light. Lack of understanding of structure-function relationships for these proteins curtails understanding of their biology and their engineering for optogenetic purposes. PI Kleinlogel first demonstrated that chimeras between bistable rhodopsin and ligand GPRCs can be functionally active and provoke a strong physiological response when expressed in vivo. PI Schertler has extensive experience in the structural analysis of rhodopsins and has successfully solved the first structure of a recombinantly expressed bistable rhodopsin. PI Hegemann has longstanding experience in the spectroscopic characterisation and engineering of photoreceptor proteins and is one of the founding fathers of optogenetics. PI Lucas pioneered cellular systems suitable for analysing spectral properties and G protein selectivity and had a leading role in elucidating the physiological role of the bistable rhodopsin melanopsin. Together, the team aims to understand how structural features of these influential photoreceptors define their bistability, bichromicity, kinetics, and G-protein selectivity (Objective 1). We will exploit this knowledge for rational engineering towards colour tuning and G protein selectivity for optogenetic tools (Objective 2) and to probe physiological functions (Objective 3). The result will be a decisive step towards a general theory of structure-function relationship in photoreceptors and will produce a new generation of powerful optogenetic tools enabling defined GPCR signalling activities in any cell type.

Mots-clés : structure based protein engineering,single particle cryo electron microscopy,time resolved serial room temperature crystallography,optogenetics,retinal proteins,g protein coupled receptor signalling,cellular functional protein analysis,photobiology,photochemistry,electrophysiology,tissue specific in vivo expression
Projet ERC : METANICHE (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1496613.0 €

Blood vessels form a versatile transport network and provide inductive signals called angiocrine factors to regulate tissue-specific functions. Blood vessels in bone are heterogeneous with distinct capillary subtypes that exhibit remarkable alterations with age. Bone is the most prevalent site of metastasis, and ageing is linked to the reactivation of dormant tumor cells (dorTCs) and metastatic relapse. Bone remodeling processes are also associated with metastatic relapse. Here, I will define the role of distinct vascular niches in regulating the fate of DTCs in bone. Finally, I will unravel the age-related angiocrine factors and identify key angiocrine signals that drive the reactivation of dorTCs. I will employ a powerful combination of advanced 3D, intravital, and whole body imaging, cell specific-inducible mouse genetics, transcriptional profiling and bioinformatics in an unprecedented manner to achieve my goals. New cutting-edge techniques such as advanced 3D and 4D bone imaging are important aspects of my proposal. I will also define the role of highly promising novel candidate age-related angiocrine signals with sophisticated inducible endothelial-specific humanised mouse models. My work will break new ground by unraveling a repertoire of age-related angiocrine factors and will contribute to a wider scientific community in bone, blood, and age-related diseases. This interdisciplinary work at the frontiers of bone, cancer and vascular biology will provide the first conceptual link between vascular ageing and bone metastasis and will contribute towards the development of therapeutic strategies for targeting DTCs in bone.

Mots-clés : bone angiogenesis,angiocrine factors,bone marrow microenvironment,metastatic relapse
Projet ERC : kiNESIS (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Body movement requires efficient transfer of force from contracting muscles to bone. Damage to the tendinous insertions is the 8th leading cause of disease burden and is the largest single cause of work loss in Europe. Historically, approaches for improving healing in these attachment units have focused on modifying repair techniques and rehabilitation protocols. These methods are proven to be very ineffective, since failure rates of as high as 94% are often reported. We have discovered that two distinct pools of progenitor cells form the tendon-to-bone attachment unit, known as “enthesis”. Moreover, we showed that these two pools are regulated separately via certain signalling pathways. These recent, yet exciting, findings gave rise to the novel idea that we can use these progenitors to regenerate the unique attachment unit, with the help also of the identified signalling pathways. The overall goal of our ERC PoC project is to take the first steps towards the development and pre-commercialisation of novel regenerative strategies for enhanced tendon-to-bone healing in the adult setting. Specifically, (1) the first target is to establish the technical feasibility of our idea by performing a series of in-vitro and in-vivo-experiments, the latter utilising a novel state-of-the-art rotator cuff enthesis injury model that we developed. If the results of our preclinical studies are successful, they will have a direct impact on future regenerative strategies for tendon-to-bone repair. (2) The second target of the kiNESIS project is to establish the commercialisation potential of our idea. The commercialisation can result in a truly revolutionising, simple and non-invasive needle-based therapy for tendon injuries.

Mots-clés : musculoskeletal conditions,enthesis regeneration,tendon to bone injuries,pre commercialization,development