Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : FLUOSWITCH (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : École normale supérieure PSL — Pays : France — Rôle : Partner
Acronyme de l'entité : ENS PSL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1148437.5 €

Biological imaging is essential for revealing the inner workings of living systems. Among the numerous imaging modalities, light microscopy has revolutionized biological research. In addition to advances in optics and detectors, imaging has benefited from the development of molecular tools to observe biomolecules in action. Although the last decade’s breakthroughs in imaging have led to new discoveries in biology, there are still extraordinary opportunities for basic and clinical research in further advancing imaging capabilities. This project proposes to develop new classes of probes to advance biological imaging and allow the study of biological processes in all their complexity. First, I propose to push the boundaries of multiplexing and super-resolution imaging in living cells developing a new class of fluorogenic probes that act as genetically encoded fluorescence on/off switches. Highly multiplexed images will be built up over sequential activation of orthogonal fluorescence on/off switches, while continuous switching will allow implementing innovative dynamic super-resolution techniques in living cells. Then, I will develop dynamic fluorescence on/off switches enabling to reveal the dynamics of intracellular processes, focusing in particular on the visualization of interaction dynamics in real-time, and the dynamic detection of endogenous molecules (e.g. proteins, nucleic acids) in living cells. The final part will be dedicated to the development of probes acting as molecular integrator switches to identify active cell circuits in whole tissues or organisms through permanent labeling of transiently activated cells. Overall, this project will enable to push back the frontiers of biological imaging providing innovative tools to interrogate quantitatively and comprehensively living systems at the molecular, cellular and network levels.

Mots-clés : biomolecular imaging,fluorescence,probe and biosensor design
Projet ERC : REDOX SHIELDS (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : Technical University of Munich — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : TUM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 719636.24 €

Biological or molecular catalysts built from Earth-abundant elements are envisioned as economically viable alternatives to the scarce noble metals that are currently used in renewable energy conversion. However, their fragility and O2 sensitivity have been obstacles to their adoption in industry. We have recently proposed O2 quenching matrices for protecting intrinsically O2-sensitive catalysts for use in anodic (oxidative) processes. We have demonstrated that even hydrogenases, the highly sensitive metalloenzymes that oxidize H2, can be used under the harsh conditions encountered in operating fuel cells. However, attempts to reverse the concept for the protection of cathodic (reductive) processes, such as H2 evolution, have been unsuccessful so far. In this case, the electrode generates the reducing agents in the form of electrons, which are needed for both H2 generation and reductive O2 quenching. The competition between the two reactions results in insufficient protection from O2 and deactivation of the catalyst. The objective is to design an alternative electron pathway that relies on H2 as a charge carrier to efficiently shuttle the reductive force to the matrix boundaries and quench the incoming O2. We will develop novel electron mediators with dual functionalities to enable the reversible H2/H+ interconversion and to achieve the complete reduction of O2 to water. We will focus on organic systems, as well as metal complexes based on Earth-abundant elements with tunable ligand spheres, to adjust their redox potentials for the desired direction of the electron flow and toward fast O2 reduction kinetics. The synthetic efforts will be supported by electrochemical modelling to predict the required properties of the redox matrix for efficient protection. After establishing the protection principle, we will demonstrate its practical use for implementing sensitive bio-catalysts for electrochemical H2 evolution under conditions relevant to energy conversion processes.
Projet ERC : ScaleCell (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : Freie Universität Berlin — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : FU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1987500.0 €

Biological processes are inherently multi-scalar: exchanging a single amino acid of a protein can affect the macroscopic behavior of a cell. A computational model that can cover these scales and simulate the time evolution of locations, interactions, and atomistic structures of biomolecules in a cell would be transformative for the understanding of biology and the optimization of biotechnological processes. This ERC project will lay the methodological groundwork for such a model. Recent breakthroughs in the long-standing problem of sampling rare transition events in molecular dynamics (MD) simulation have enabled us to simulate biomolecular processes such as folding and binding with atomistic models. The PI has co-pioneered the widely-used Markov State Models (MSMs) that combine extensive distributed MD simulations towards models of the molecular kinetics. Using these methods, we have demonstrated that protein-protein association can be simulated and timescales of seconds can be reached in all-atom models of small protein systems. However, these methods have fundamental limitations to scale to the large biomolecules and the long length-scales involved in cellular signaling. To address these limitations, we will develop the following key technologies and disseminate them in open software: 1. A model that describes protein kinetics as a network of local switches which will overcome scaling limitations of MSMs that suffer from an exponential increase of parameters for large systems. 2. An “effective force field for cells” that predicts structure and kinetics of multi-body protein interactions based on simulations of relatively few protein interactions. 3. A multi-scale method to embed atomistic kinetic models in whole-cell reaction-diffusion simulations. We will employ these methods and, in collaboration with leading experimentalists, investigate how the mechanochemical protein dynamin couples atomic-detail structure changes to membrane constriction in endocytosis.

Mots-clés : theory and method development in chemical physics and computational chemistry
Projet ERC : WACONDY (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Centrale Lyon — Pays : France — Rôle : Partner
Acronyme de l'entité : EC Lyon
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 65625.0 €

Biology is a source of exciting mathematical challenges. Likewise, there is a strong demand from biologists for rationalizing and quantifying their fascinating observations and for testing hypotheses via theoretical models. PDE have proven powerful for these purposes. The main goal of the WACONDY project is to expand the theory of Hamilton-Jacobi (HJ) equations and related ones to encompass recent investigations in ecological and evolutionary dynamics. The asymptotic analysis of wave propagation in structured populations, along with that of equilibria in quantitative genetics models, have generated new problems that fall outside of the scope of the current theory. These novel HJ equations arise in regimes that are analogous to semi-classical analysis in physics. On the one hand, they are valuable for biology because the associated dynamics can be reduced to simpler rules than the original problem. On the other hand, they do not fit in the classical theory of viscosity solutions. Hence, innovative techniques are needed to achieve their deep understanding. The envisioned outcomes of the project are: a comprehensive analysis of non-local HJ equations arising in kinetic reaction-transport equations and reaction-diffusion equations for dispersal evolution; the asymptotic analysis of quantitative genetics models balancing diversity among offspring and selection of the fittest individuals, in the regime of small variance. The case of sexual reproduction will be emphasized, as the associated limit problem unveils novel features, beyond the HJ formulation. The design of asymptotic-preserving numerical schemes for this new class of equations will complement the program. Beyond tackling these fundamental aspects, the project aims to open new interdisciplinary research directions. We anticipate contributions to diverse topics such as collective waves of micro-organisms, propagation of genetically engineered organisms, and patterns of adaptation in changing environments.

Mots-clés : mathematical biology,kinetic equations,hamilton jacobi equations,wave propagation,quantitative genetics,asymptotic preserving schemes
Projet ERC : Bio-Plan (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Eindhoven University of Technology — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : TU/e
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3083625.0 €

Biomechanical interactions between cells and their environment are essential in almost any biological process, from embryonic development to organ function to diseases. Hence, biomechanical interactions are crucial for health and disease. Examples are hydrodynamic interactions through fluid flow, and forces acting directly on cells. Existing methods to analyze and understand these interactions are limited however, since they do not offer the required combination of precisely controlled flow and accurate applying and sensing of forces. Also, they often lack a physiological environment. A breakthrough in biomechanical analysis is therefore highly needed. We will realize a novel microfluidic platform for biomechanical analysis with unprecedented possibilities of controlling fluid flow and applying and sensing time-dependent forces at subcellular scales in controlled environments. The platform will be uniquely based on bio-inspired magnetic artificial cilia, rather than on conventional microfluidic valves and pumps. Cilia are microscopic hairs ubiquitously present in nature, acting both as actuators and sensors, essential for swimming of microorganisms, transport of dirt out of our airways, and sensing of sound, i.e. they exactly fulfill functions needed in biomechanical analysis. We will develop novel materials and fabrication methods to realize microscopic polymeric artificial cilia, and integrate these in microfluidic devices. Magnetic actuation and optical readout systems complete the platform. We will apply the novel platform to address three fundamental and unresolved biomechanical questions: 1. How do hydrodynamic interactions with actuated cilia steer cellular and particle transport? 2. How do local and dynamic mechanical forces on cells fundamentally influence their motility and differentiation? 3. How do hydrodynamic interactions between cilia steer embryonic development? This unique platform will enable to address many other future biomechanical questions.

Mots-clés : microfluidics,biomechanics,analysis platform,micro actuators,mechanotransduction,cilia
Projet ERC : CardioZoom (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : University of Groningen — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : RUG
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1498514.0 €

Biophysical computational models of the cardiovascular system need to be adapted to each particular patient from clinical data. The state-of-the-art imaging method for assessing cardiovascular diseases is Magnetic Resonance Imaging (MRI), which is hence the preferred source of data for the personalization of the models. However, MRI is still not able to reliably image the kinematics of thin structures like cardiac valves and the arterial wall. Moreover, MRI measurements of the 3D kinematics of the heart is a challenging task. These restrictions hamper the clinical translation of patient-specific modeling. Therefore, a new paradigm for model personalization is urgently needed. The ambition of CardioZoom is to propose novel methods for biophysical parameter estimation in computational models of the heart, large vessels and valves using MRI data acquired in very short scan times. The approach will be based on the deep integration imaging and biophysical principles, relaxing the constraints of standard cardiovascular imaging implying long MRI scans. Extensive validations using experimental (phantom) data will be performed and tests on volunteer and patients data are planned. The findings of CardioZoom will allow obtaining clinically feasible, detailed characterizations of the cardiovascular system.

Mots-clés : cardiovascular computional modeling,inverse problems,medical imaging
Projet ERC : SynBioBrain (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
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 : 1998025.0 €

Biosensors detect compounds using a biological component combined with a physio-chemical detector. Using synthetic biology, we can now engineer bacteria into whole-cell biosensors where sensing, transduction and output occur within the living cell. Applications include the detection of harmful environmental agents, bioprocess monitoring, and detecting medically relevant biomarkers. As we move towards more sophisticated applications, single channel read-out will be replaced with sensors that have multiple inputs and more complex information processing capabilities. Whilst digital logic within a single strain of bacteria can be implemented, consortia offer a powerful alternative, where information is integrated and processed in a distributed fashion. This proposal sets out a research project that will construct biological computers formed from engineered bacterial populations that communicate using quorum sensing molecules. Information from multiple biosensor inputs will be integrated and processed by the biocomputer, the output of which will be spatial patterning. The architecture will be based on cellular automata, which can perform any computation, including logic and temporal logic operations, memory and counting, all of which can be used to distinguish states in complex biological and chemical environments. Our biocomputers will be housed in microfluidic devices using hydrogel structures to create two and three dimensional regular arrangements. As a proof-of-concept, we will develop a biocomputer for the analysis and monitoring of intestinal and microbiota health through stool samples. Sensors for inflammation, pH and short chain fatty acids will be combined into a device that can indicate whether an individual has inflammatory bowel disease or irritable bowel syndrome. A low-cost device for use at home, which distinguishes between these conditions, could potentially save the global health care industry billions of dollars in unnecessary diagnostic treatments.
Projet ERC : SOL (Horizon 2020, appel 2020, Synergy grants)
Entité participante : University of Bern — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 0.0 €

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 : BodyMemory (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : University of Tübingen — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1462011.51 €

Body memory is the sum of all past bodily experiences that are stored in memory and influence behavior. Body memories influence our daily life, for example when we remember injuries, accidents, or moments of bodily comfort, and they affect mental health, for example when they cause psychosomatic symptoms, depression, or anxiety. Scientific knowledge on the neuroanatomical pathways and neuronal mechanisms that underlie human body memory is scarce, partly because offline representations of bodily experiences are challenging to study experimentally. Recently, I used 7 Tesla functional magnetic resonance imaging (7T-fMRI) to detect and describe offline representations of tactile sensations at the skin in human somatosensory cortex. These representations are fine-grained, precise, and replicable, and provide empirical evidence that offline representations of bodily feelings can be described by means of 7T-fMRI. In this research project, I will combine my own knowledge and experience in ultra-high field imaging, topographic mapping, psychophysics, and embodiment with recent advances in episodic memory research to target three research questions: (i) Which neuronal mechanisms underlie the storage and retrieval of somatosensory experiences?, (ii) How do stored sensory experiences contribute to psychosomatic symptoms?, and (iii) How can we treat psychosomatic symptoms triggered by maladaptive body memories? Offline representations of tactile experiences and associated emotions will be used as a model system to systematically investigate the storage, retrieval, and intervention-induced plasticity of somatosensory body memories and associated emotions in healthy adults and in clinical populations. The research agenda I propose here will use state-of-the-art scientific tools and methods to gain basic and applied insights into a novel and far reaching research field with the final goal to develop interventions to change stored body memories.

Mots-clés : embodiment,embodied memories,7 tesla fmri
Projet ERC : VitruVius (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : Partner
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 160625.0 €

Body size is an intrinsic property of living organisms that is intimately linked to the developmental program to produce fit individuals with proper proportions. Final size is the result of both genetic determinants and sophisticated mechanisms adapting size to available resources. Classical regeneration and transplantation experiments have established that different body parts grow according to autonomous programs, challenging the concept of systemic and harmonious growth. Therefore, coordination mechanisms must ensure that all parts have reached appropriate final size before animals stop growing. The main objective of this program is to tackle the mechanisms ensuring growth coordination and size determination. To tackle these questions, we propose to bring together physiology, genetics, advanced imaging and modelling approaches in an unprecedented integrated project. We will develop these approaches on the Drosophila model where we gained expertise, and will develop the vertebrate model Ambystoma mexicanum (axolotl) well adapted for limb growth and regeneration studies. Three major aims will be addressed: 1- We will explore the mechanisms coupling the developmental clock with organ growth. 2- We will dissect the mechanisms allowing inter-organ growth coordination both in response to abnormal growth (injury/neoplasm) and in the course of normal development (control of developmental instability). 3- We will use our knowledge acquired on insect models to develop Ambystoma mexicanum (axolotl) as a vertebrate model for organ growth coordination. We believe this project brings together novel and complementary expertise that will contribute to broader understanding of the fascinating question of body growth and final size assessment.

Mots-clés : growth control,developmental timing,insulin,igf signaling,ecdysone signaling