Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : NMR-DisAgg (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499956.0 €

Molecular chaperones are a diverse group of proteins critical to maintaining cellular homeostasis. Aside from protein refolding, it has recently been discovered that certain combinations of human chaperones can break apart toxic protein aggregates and even amyloids that have been linked to a host of neurodegenerative diseases. The first chaperones in this disaggregation reaction that are responsible for recognizing and performing initial remodeling of aggregates, are members of the Hsp40 (DnaJ) and small heat shock protein (sHSP) families. Very little, though, is known regarding how these chaperones perform their functions, and characterization of sHsp- and DnaJ-substrate complexes by most structural techniques has proven extremely challenging, as most chaperones are dynamic in nature and typically operate through a series of transient interactions with both their clients and other chaperones. The advanced NMR techniques used in our lab, however, are ideally suited for the study of these exact types of dynamic systems, and include recently developed experiments (CEST, CPMG) that allow us to monitor the transient and low populated protein states typical of chaperone-chaperone and chaperone-client interactions, as well as to study the structure of these potentially very large protein complexes (methyl-TROSY). By exploiting these NMR methodologies and additional, novel labeling schemes, we will characterize, for the first time, the recognition and substrate remodeling performed by the many members of the DnaJ and sHsp chaperone families on their clients. We will then take these approaches one step further and develop real time NMR experiments to observe the client remodeling performed over the course of the disaggregation reaction itself. By combining advanced NMR with biophysical and functional assays, we ultimately aim to identify the specific sets of chaperones that, with the Hsp70 system, protect our cells by dissolving disease-linked aggregates and amyloid fibers.

Mots-clés : protein nmr spectroscopy,molecular chaperons,protein disaggregation
Projet ERC : EMC2 (Horizon 2020, appel 2018, Synergy grants)
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 825206.0 €

Molecular simulation has become an instrumental tool in chemistry, condensed matter physics, molecular biology, materials science, and nanosciences. It will allow to propose de novo design of e.g. new drugs or materials provided that the efficiency of underlying software is accelerated by several orders of magnitude. The ambition of the EMC2 project is to achieve scientific breakthroughs in this field by gathering the expertise of a multidisciplinary community at the interfaces of four disciplines: mathematics, chemistry, physics, and computer science. It is motivated by the twofold observation that, i) building upon our collaborative work, we have recently been able to gain efficiency factors of up to 3 orders of magnitude for polarizable molecular dynamics in solution of multi-million atom systems, but this is not enough since ii) even larger or more complex systems of major practical interest (such as solvated biosystems or molecules with strongly-correlated electrons) are currently mostly intractable in reasonable clock time. The only way to further improve the efficiency of the solvers, while preserving accuracy, is to develop physically and chemically sound models, mathematically certified and numerically efficient algorithms, and implement them in a robust and scalable way on various architectures (from standard academic or industrial clusters to emerging heterogeneous and exascale architectures). EMC2 has no equivalent in the world: there is nowhere such a critical number of interdisciplinary researchers already collaborating with the required track records to address this challenge. Under the leadership of the 4 PIs, supported by highly recognized teams from three major institutions in the Paris area, EMC2 will develop disruptive methodological approaches and publicly available simulation tools, and apply them to challenging molecular systems. The project will strongly strengthen the local teams and their synergy enabling decisive progress in the field.

Mots-clés : high performance algorithms,mathematics of molecular simulations,error analysis in numerical simulations
Projet ERC : MaMoGH (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : Ruhr University Bochum — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : RUB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1254676.19 €

Monocultures are one of the great projects of industrial modernity. From the corn fields of Iowa to date palms in the Sahara, from banana plantations in the Americas to eucalyptus trees in India – wherever we look, we find large production regimes that focus on a single commodity. They supply the lion’s share of the world’s food and create a plethora of economic, social, political and environmental problems. However, there is a great paradox behind the global hegemony of monocultures: they thrive in the absence of a clear paradigm. There is no biological theory of monoculture – and plenty of evidence for the benefits of biological diversity. The project brings historical research to bear in a field that is traditionally the province of agronomists and activists. In the best tradition of global history, it reveals what isolated case studies have failed to see: problems, solutions and actors were surprisingly similar in otherwise different monocultures around the world. Based on carefully selected case studies and intensive communication with experts from forestry and the agricultural sciences, the project identifies the common patterns in the trajectories that monocultures followed around the world and uses that for a new interpretation of the growth and resilience of monocultures that only a historian can provide: a global narrative of recurring crises, of externalizing costs, and of an ever-growing path dependency. Monocultures are stumbling on in spite of the costs because the price of reverting course seems even greater. Outputs include five monographs, culminating in a path-breaking synthesis. The project seeks to challenge existing boundaries between historical subdisciplines and explore the common ground between agricultural history, forest history, environmental history, economic history, and the history of science and technology. It also aims to make history relevant in a 21st-century world where organic production will face unprecedented challenges.

Mots-clés : environmental history,agricultural history,forest history
Projet ERC : SKYNOLIMIT (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Koç University — Pays : Turquie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Moore’s Law drove the technology revolution for more than five decades and left no aspect of our lives untouched. State-of-the-art computation relies on transistors, whose dimensions or power consumption could no longer be reduced. Nevertheless, growing need for information processing, battery-constrained internet-of-things devices and wireless connectivity necessitates discoveries of nanoelectronic building blocks with novel physics. Thus, fundamental breakthroughs are needed in highly power-efficient non-volatile computational elements that meet the speed, bandwidth and scalability requirements of microelectronics industry. Using electronic spins for non-volatile computation could offer very diverse new device physics and architectures to meet these requirements. In SKYNOLIMIT project, I aim to experimentally demonstrate ultra-wideband, ultralow-power and non-volatile logic circuit architectures that operate based on nanoscale spins called magnetic skyrmions. Skyrmions are nanoscale spin structures that allow for room temperature computation and memory functions near thermodynamic limits while being robust against fabrication imperfections and stray magnetic fields. In this project, (1) I first computationally model, fabricate and test the novel functional nanomaterials with giant spin-orbit coupling and low damping to achieve all-electric generation/detection and processing of skyrmions using multilayers of topological insulators and/or 2D transition metal dichalcogenides on insulating rare earth iron garnet films. Second, (2) I plan to experimentally demonstrate skyrmion processors including signal generators, logic gates, registers, and fast Fourier transformers. Third, (3) I plan to experimentally implement neural network hardware using skyrmionics. Thus, high-speed and ultra-wideband 2D skyrmionics could help reduce power consumption, extend mobile battery life by a few orders of magnitude and help spintronics become a part of mainstream electronics.

Mots-clés : garnet,spintronics,skyrmion
Projet ERC : IntuitiveBCI (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Imperial College London — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

More than 25% of people over the age of 50 suffer a movement disorder; many of them have a functional disability as a result. Intracortical Brain-Computer Interfaces (BCIs) that extract or “decode” the user’s intent based on recordings from tens or hundreds of cortical neurons have enabled paralyzed patients to control computer cursors, robots, or even their own limbs just by modulating their neural activity. Despite these successes, BCI control still falls short compared to natural limb control: it is far less skilled, and it requires significantly more mental effort. My goal is to overcome these two limitations through a novel “Intuitive BCI” that leads to enhanced control compared to current approaches. Rather than follow the dominant trends of developing new decoder algorithms and interface technologies, I will adopt a unique, previously unexplored approach: to leverage the brain’s own distributed resources to control automatic movements in a skilled and intuitive manner requiring little mental effort. Automatic movements depend critically on subcortical brain structures whose activity is not probed by current cortical BCIs. To develop my novel approach to BCI based on the neural control of automatic movements, I will combine: 1) recent breakthroughs to record from thousands of neurons across the mouse brain; 2) a novel theory to model neural population activity that I have helped establish; and 3) new experimental tasks to isolate the cortico-subcortical information underlying automatic movements. This information will provide inputs to the proposed Intuitive BCI. I seek to prove that it leads to more skilled and intuitive control than current approaches, even allowing users to multi-task –an unprecedented feat in the field. This timely, multidisciplinary research will push BCI control forward, beyond current state-of-the-art approaches limited to cortical control. It will also help realize BCI’s promise to improve the quality of life of neurological patients

Mots-clés : brain computer interface,neural engineering,biomedical engineering,neuroprosthetics,neural control of movement,neural population activity,neural manifolds,brain machine interface
Projet ERC : EVICARE (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University Medical Center Utrecht — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1997297.99 €

More than 3.5 million people are newly diagnosed with heart failure every year in Europe with a long-term prognosis of 50% mortality within 4 years. There is a major need for more innovative, regenerative therapies that have the potential to change the course of disease. My hypothesis is that we can recondition heart failure by stimulating cardiac repair with extracellular vesicles that are derived from progenitor cells. In my laboratory, extracellular released vesicles containing a cocktail of stimulating factors, are amongst the most potent vectors for cardiac repair. To achieve a sustainable and long-term therapeutic effect of these vesicles and enhance cardiac function by stimulating myocardial repair, we will 1) improve local cardiac delivery of progenitor cell-derived extracellular vesicles, 2) understand the mechanism of action of extracellular vesicles, and 3) stimulate extracellular vesicles release and/or production by progenitor cells. These questions form the rationale for the current proposal in which we will co-inject extracellular vesicles and slow-release biomaterials into the damaged myocardium. By subsequent genetic tracing, we will determine fate mapping of injected vesicles in vivo, and perform further mechanistic understanding in in vitro culture models of targeted and identified myocardial cell types. Moreover, we will upscale the vesicles production by progenitor cells further via bioreactor culturing and medium-throughput screening on factors that stimulate vesicles release. The use of stem cell-derived extracellular vesicles to stimulate cardiac repair will potentially allow for an off-the shelf approach, including mechanistic understanding and future clinical use. Additionally, since these vesicles act as a natural carrier system outperforming current artificial drug delivery, we might understand and mimic their characteristics to enhance local (RNA-based) drug delivery systems for cardiovascular application.

Mots-clés : extracellular vesicles,microrna therapeutics
Projet ERC : BENOVELTY (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Enamine (Ukraine) — Pays : Ukraine — Rôle : PI
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 1997500.0 €

More than 500 of all existing drugs are phenyl-containing organic molecules. During the recent years, however, pharmaceutical companies struggle to deliver novel drugs to the market, because of the lack of innovative practical approaches towards novel drug-like “chemical space.” In this project, we will address this issue by developing novel saturated bioisosteres for ortho- and meta-substituted benzenes, and incorporate them into several known drugs (intiinflamatory Aceclofenac, antiviral Tipranavir, antihypertensive Oxprenolol, etc) to provide novel patent-free analogues with improved physico-chemical and biological properties.

Mots-clés : benzene bioisosteres,saturation,photochemistry,bicyclo 1 1 1 pentanes,cyclobutanes
Projet ERC : RASATaC (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : University of Turku — Pays : Finlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

More than a quarter of all cancers are driven by mutations in the RAS family of genes. Considering the key role of these oncogenes, and despite intensive effort, no effective anti-RAS strategies have successfully made it to the clinic. In our ERC-CoG project, we found that a class of scaffold proteins, expressed in cancer, bind to active/mutated forms of RAS proteins to moderate RAS signalling. Accordingly, we find that loss of one of the scaffolding protein isoforms in RAS-mutant cancers triggers cytotoxic signalling, leading to cell death. As such, drugging this scaffold protein could not only i) represent a completely innovative approach to target RAS-driven cancers that exploits the oncogene’s function, but also ii) deliver the first truly effective cancer treatment for patients that do not respond to current standards of care. In this ERC-PoC, we aim to prove that therapeutic targeting of the scaffold protein is effective in vivo, and to explore the commercial avenues to exploit this finding.

Mots-clés : cancer,oncogene,therapeutic targeting
Projet ERC : NeuroPioneers (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : PI
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 1996947.0 €

Most adult cortical dynamics are dominated by a minority of highly active neurons distributed within a silent neuronal mass. If cortical spikes are sparse, spiking of single distinct neurons can impact on network dynamics and drive an animal’s behavior. It is thus essential to understand whether this active and powerful minority is predetermined and if true to uncover the rules by which it is set during development. I hypothesize that birthdate is a critical determinant of neuronal network function into adulthood. More specifically, I reason that neurons that are born the earliest are primed to participate into adult network dynamics. The goal of this proposal is to challenge this original hypothesis, which is considerably fed by our past work aiming at understanding how cortical networks function and assemble during development. Hence, we have shown that an early birthdate: (1) specifies the specialization of GABA neurons with a hub function, that orchestrate perinatal network dynamics in the mouse hippocampus (Bonifazi et al. 2009) and develop into long-range projecting GABA neurons into adulthood (Picardo et al. 2011); (2) delineates a subtype of CA3 glutamate neuron with a “pacemaker” function in the absence of fast GABAergic transmission (Marissal et al. 2012). We will analyze the structure and function of early born GABA and glutamate neurons, in the adult mouse hippocampus, mainly in vivo, where the extensive and long-range connectivity of these cells is preserved. To this aim, we have translated from the in vitro to the in vivo situation, our multidisciplinary method to investigate structure-dynamics relationship in cortical networks. Using this approach, we have recently shown that, in the absence of external landmarks, distance is encoded within the hippocampus in recurrent and self-circumscribed sequences of neuronal activation. Our proposal will specifically examine the recruitment of early born neurons in this sparse network dynamics pattern.

Mots-clés : gaba imaging hippocampus networks hub spatial representation place cells
Projet ERC : CoPathoPhage (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Tel Aviv University — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2200000.0 €

Most bacterial pathogens are lysogens, namely carry DNA of active phages within their genome, referred to as prophages. While these prophages have the potential to turn under stress into infective viruses which kill their host bacterium in a matter of minutes, it is unclear how pathogens manage to survive this internal threat under the stresses imposed by their invasion into mammalian cells. In the proposed project, we will study the hypothesis that a complex bacteria-phage cooperative adaptation supports virulence during mammalian infection while preventing inadvertent killing by phages. Several years ago, we uncovered a novel pathogen-phage interaction, in which an infective prophage promotes the virulence of its host, the bacterial pathogen Listeria monocytogenes (Lm), via adaptive behaviour. More recently, we discovered that the prophage, though fully infective, is non-autonomous- completely dependent on regulatory factors derived from inactive prophage remnants that reside in the Lm chromosome. These findings lead us to propose that the intimate cross-regulatory interactions between all phage elements within the genome (infective and remnant), are crucial in promoting bacteria-phage patho-adaptive behaviours in the mammalian niche and thereby bacterial virulence. In the proposed project, we will investigate specific cross-regulatory and cooperative mechanisms of all the phage elements, study the domestication of phage remnant-derived regulatory factors, and examine the hypothesis that they collectively form an auxiliary phage-control system that tempers infective phages. Finally, we will examine the premise that the mammalian niche drives the evolution of temperate phages into patho-adaptive phages, and that phages that lack this adaptation may kill host pathogens during infection. This work is expected to provide novel insights into bacteria-phage coexistence in mammalian environments and to facilitate the development of innovative phage therapy strategies.

Mots-clés : intracellular bacterial pathogen,bacteriophage,prophage,listeria monocytogenes
Projet ERC : GHOSTS (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Karlsruhe Institute of Technology — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : KIT
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 973067.75 €

Most biological tissues are optically opaque, largely precluding access by light microscopy. In stark contrast, some living tissues and organisms are highly transparent. Examples include many deep-sea fish, your retina, and cells that we exposed to directed evolution. Here we propose to uncover the genetic basis of tissue transparency, such that living cells and tissue cultures can be optically cleared by precision genetics. For this we will combine insights into origins of retina transparency, and a set of unique methods, to answer the question how genetically cells become more transparent during directed evolution. Specifically, we will use a three-fold approach to find transparency genes that do not compromise cellular integrity. For this we will use i) directed evolution towards transparency while co-selecting for cell fitness, ii) extensive phenotyping of transparent cells, both optically and functionally, and iii) use of transcriptomics to rule out stressed cells, and those that deviate too much from wildtype gene expression profiles. Knowing about physiological transparency genes will allow unprecedented insights into living tissues. If model tissues in the lab were just 1% as transparent as some glass-like fish found in the deep sea, optical microscopes could unleash their full potential, and enable high resolution views into developmental processes in their native environment. We see further transformative potential especially in the fields of organotypic tissue models, functional brain imaging, as well as pharmaceutical screens in 3D tissue cultures.