Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : EnBioSys (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 1935240.0 €

All living systems function out of thermodynamic equilibrium and require a continuous supply of energy. To understand how cells and organisms function, we need to determine how metabolic energy is partitioned among the complex array of cellular processes that are necessary for life at any scale, from isolated biochemical networks to quiescent and highly proliferative cells to organismal growth and development. To investigate the energetics of living systems, I established calorimetry to measure the energy exchanged in the form of heat between biological systems and their environment. By combining these measurements with specific perturbations, I have shown that the energetic costs associated with a given biological process can be calculated, and thus, provides a means towards understanding the energetics of biological systems. This proposal aims to understand the energetic costs of accurate cell signaling, and of homeostasis, proliferation, and growth of cells and organisms. It will further investigate how these biological systems are governed by energetic trade-offs. First, the trade-off between energy dissipation and accuracy of biochemical signaling pathways. Second, the trade-off between power and yield during cell growth and organismal development. Specifically, I will: 1) Develop approaches to quantify the overall energetics of biological systems 2) Elucidate the role of energy dissipation on the accuracy and reproducibility of cell cycle signaling 3) Determine how energetics drive embryonic development and cell growth This work will overcome the current lack of non-invasive techniques to quantitatively measure metabolic rates, especially rates of energy conversion and dissipation in biological systems. The results will yield quantitative thermodynamic data needed to determine the energetics of biological systems and will be essential for kinetic growth studies of normal and diseased systems.

Mots-clés : calorimetry,thermodynamics,energetic trade off,homeostasis,growth,embryonic development,physics of biological systems
Projet ERC : CBASS (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : University of St Andrews — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1785866.0 €

All living things are subject to attack by viruses. Cells have evolved many different immune systems to protect themselves, including the adaptive and innate immune systems of vertebrates and the CRISPR and restriction:modification systems of bacteria. Viruses have developed potent countermeasures to subvert these systems, and this perpetual arms race has been a strong driving force in evolution throughout the history of life on Earth. CBASS (cyclic-oligonucleotide-based antiphage signalling systems) is a newly discovered bacterial immune system with evolutionary links to the eukaryotic cGAS-STING innate immune pathway. CBASS generates an astonishing array of cyclic di- and tri-nucleotide signalling molecules that in turn activate a diverse range of effector proteins to combat phage infection. These cyclic nucleotide second messengers thus lead to life or death decisions for infected cells. CBASS are abundant in pathogens and the microbes that dominate the human digestive system: this microbiome and the viruses that infect it are now implicated in diverse aspects of human health. This is a powerful and complex defence system, but fundamental aspects are not understood. How is viral infection detected by bacteria, triggering cyclic nucleotide production? What are the consequences for the cell: does activation inevitably lead to cell death, or is there a mechanism to switch it off? What role does protein modification play? Furthermore, how do viruses overcome CBASS defence? These questions will be addressed using a cutting-edge combination of structural and molecular biology, bioinformatics, biochemistry and microbiology. We propose a ground-breaking study of CBASS defence, with a focus on discovery of new enzymes, pathways and mechanisms. This work will open up new paradigms in bacterial cell signalling with broad implications for our understanding of microbial physiology, infection and the evolution of immune systems.

Mots-clés : cyclic nucleotide,crispr,abortive infection,bacteriophage
Projet ERC : NeuroVisEco (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : University of Sussex — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

All visual systems are specialised to best serve an animal’s sensory niche, yet how such specialisations are achieved through phylogenetic and developmental adaptations of the ‘common vertebrate visual system blueprint’ are poorly understood. I will study these adaptations in the visual system of zebrafish. I will use two-photon functional imaging and computational modelling to investigate how the visual system of zebrafish samples and processes behaviourally meaningful stimuli in the natural world. I will then use optogenetic manipulations while zebrafish navigate a virtual reality environment to directly probe the role of visual circuits in driving behaviour. Specifically, I will pursue four Aims: 1. What is the zebrafish eye designed to see? 2. How does the fish retina form feature selective output channels? 3. What does the fish’s eye tell the fish’s brain? 4. How does visual input to the brain lead to behaviour? Visual specialisations begin in the optics and movements of the eyes, and are subsequently deeply rooted in every step of neuronal computation. Therefore, I will study visual processing at these different organisational levels. Here, the highly ‘visual’ zebrafish present a powerful model. They (i) offer exquisite genetic tools to record and manipulate neurons, (ii) have transparent larval stages permitting optical access to the entire nervous system and (iii) there is a large array of well-studied and easily quantifiable visual behaviours. In addition, zebrafish undergo two distinct life-stages, from larva to adult - with distinct lifestyles in different visual environments and hence different feature-detection requirements. Comparison of processing strategies employed by the (a) larval and (b) adult zebrafish visual system with that of other species, including a complementary database already recorded in mice (c), will lead to an increasingly generalised understanding of biological vision.

Mots-clés : vision,visual ecology,system analysis,computational modelling,optogenetics,behavioural ecology
Projet ERC : Allosteric-CRISPR (Horizon 2020, appel 2020, 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 : 1399632.0 €

Allostery is a fundamental property of proteins, which regulates biochemical information transfer between spatially distant sites. Many emerging allosteric targets are large protein/nucleic acid complexes responsible for genome editing and regulation, whose underlying signaling remains poorly understood. Here, we focus on CRISPR-Cas9, a large nucleoprotein complex widely employed as a genome editing tool with enormous promises for medicine and biotechnology. In this system, an intricate allosteric signaling is suggested to span the multi-domain Cas9 protein and its associated nucleic acids, controlling the system’s function and specificity. However, in spite of extensive experimental characterization, the molecular basis for this allosteric response are largely unknown, hampering also efficient engineering for improving its genome editing capability. Allosteric-CRISPR will investigate the allosteric regulation in CRISPR-Cas9 by introducing a novel synergistic approach. This will implement the combination of state-of-the-art theoretical methods, including enhanced and multiscale approaches based on classical and ab-initio methods, with network models derived from graph theory and novel centrality analyses that are emerging as powerful to investigate allostery. This will create an innovative protocol that will enable determining the allosteric network of communication over multiple timescales, as well as the relation between allostery and catalysis, which remains unaddressed through classical approaches. This novel way to describe allostery can impact future studies of large nucleoprotein complexes, including newly discovered CRISPR systems, which are governed by similar allosteric rules and hold tremendous potential for genome editing. Finally, by delivering fundamental knowledge on the basic mechanisms underlying genome editing, Allosteric-CRISPR will help the design of improved genome editing tools, impacting their application across the field of life sciences.

Mots-clés : allostery,crispr cas9,protein,nucleic acid interactions,molecular dynamics
Projet ERC : AT2 (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer science and informatics
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 : 150000.0 €

Although Nakamoto’s original blockchain protocol has spurred significant innovation and financial interest in the last decade, its energy consumption becomes problematic. Besides, transaction latencies are prohibitively high and the system sustains a very low throughput. We have witnessed hundreds of alternative solutions in the last decade. Each seeks to reduce energy consumption, to obtain lower latency, or to improve throughput. All proposed alternatives, however, sacrifice either trustworthiness or efficiency. In retrospect, this is not surprising. All these solutions seek to solve a notoriously difficult problem: consensus. In short, the set of nodes in the network have to agree on the same position of a block in the chain, despite the possibility of malicious behaviour of some of the nodes, or network delays. The consensus problem has been the most studied problem in distributed computing, and many impossibility and lower bound results were established. These results translate into inherent trade-offs between trust and efficiency. In the context of our ERC AOC (Adversary-Oriented Computing) project (advanced grant), we worked on classifying distributed computing problems according to their hardness. While doing so, we revisited the issue of implementing a trustworthy payment system, i.e., the problem solved in Nakamoto’s paper. This led us to a very interesting discovery: Current blockchain protocols are tackling a problem, i.e., consensus, which is unnecessarily strong for their purpose of building a payment system. More specifically, we have shown that it is enough to solve a problem called secure causal broadcast to implement trust in any tokenized application. This is significantly simpler than consensus. We devised a generic asynchronous protocol to solve the secure causal broadcast problem, which we called AT2, Asynchronous Trustworthy Transactions, which we patented. The goal of this project is to pave the path to its commercialization.

Mots-clés : decentralization,trust,asynchrony,blockchain,transactions
Projet ERC : NIMBUS4CIP (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Amsterdam University Medical Centers — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Although cancer in pregnancy (CIP) is rare (one in 1000-2000 pregnancies), it has an important impact on society as it annually affects more than 200,000 pregnant women worldwide. The ERC-CoG project “CRADLE”, has led to the finding that management of cancer in pregnancy requires a specialized multidisciplinary care of not only physicians within the oncology field but also in gynaecology, obstetrics, perinatology and psychology. However, as CIP is a rare event, most physicians are rarely confronted with pregnant women with cancer and therefore, lack the expertise manage these cases. Moreover, many geographical and logistic barriers might impede community-based hospitals and/or patients access to multidisciplinary tumour boards in referral hospitals. This results in a staggering number of patients that are treated with suboptimal care. As a result of these findings, Prof. Amant and his CRADLE team spearheaded the creation of an email-based Dutch-Belgian tumor advisory board, that is highly integrative and specialised in the cancer in pregnancy field. The main aim of this board is to remotely discuss CRADLE cases but also to provide specialized advice to hospitals without specialized resources or with important geographical and logistic barriers. In NIMBUS4CIP, we plan to validate the societal and commercial value of this Dutch-Belgian cancer in pregnancy platform. First, we will technically optimize the board by creating a web-based software (weCRADLE) that will streamline and improve the efficiency of case management. Next, we will validate in a prospective pilot study whether patient management using weCRADLE leads to improved oncological, obstetrical and neonatal outcomes. Finally, we will evaluate weCRADLE’s intellectual property position and the commercialization potential as a tool to remotely offer support to non-specialized physicians.

Mots-clés : tumor board,software,cancer,pregnancy
Projet ERC : Fluodamage (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 143200.0 €

Although elastomers are widely used in load-bearing engineering applications where lightweight and flexibility is essential, they are typically designed thicker than they need to be, due to a poor prediction of their lifetime in use. The loss of flexibility and extensibility results from individual covalent bond scission in the bulk of the material. When the extent of bond scission increases or localizes in specific spots, the rubber becomes brittle and can break catastrophically, potentially causing an accident. Detecting the early stage progressive molecular scale damage during use is impossible with current techniques using ultrasounds or X-rays. Within the framework of the ERC project CHEMECH we have precisely developed a method to detect, image and quantify bond breakage. This technique is based on tagging model materials with molecular probes (i.e., fluorophores) that become fluorescent when they break in response to a mechanical force. The goal of the current proposal is to incorporate the fluorophores in a variety of elastomers and to develop a novel methodology for non-destructive visualization and quantification of early damage by bond scission occurring in elastomers during cyclic mechanical testing. Compared to existing ultrasound and X-ray solutions, our technology detects degradation occurring at a much smaller scale (10 nm), can localize the damage more precisely and is non-destructive allowing the monitoring of the damage evolution in time. This information can then be used to refine the prediction of lifetime to design parts lighter and with less material, to schedule maintenance and part replacement more accurately, preventing catastrophic failures while saving time and money and finally to find new materials design strategies and expand the use of lightweight polymeric materials into new applications where they could replace metals or ceramics.

Mots-clés : organic chemistry,polymer physics,fracture mechanics,materials engineering,non destructve testing,fluorescence
Projet ERC : Multiscreen (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 139690.0 €

Although some biotechnologies have made huge strides e.g. in automation, data generation, or biochemical methods, cell handling still uses antiquated methods that limit the scale at which assays can be performed. Our ERC-funded microfluidics work has lead to cutting-edge microdroplet manipulation tools for cell handling: While working with 3D cell cultures, we have recently shown that we can obtain great increases in both throughput and detail, while reducing the sample use and the machine footprint. In addition to these quantitative leaps, the microfluidic format also allows qualitatively new biological constructs to be explored by making significant steps towards the organ-on-a-chip framework. The current project therefore aims to show how the technologies developed in our lab can function together in an integrated cell screening platform. This will require demonstrating a convincing proof of concept of the hardware, software, and workflow, in addition to demonstrating the added value to different industries.

Mots-clés : microfluidics,drug screening,bio engineering,3d cell culture
Projet ERC : CitizenGap (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : University of Amsterdam — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UvA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499996.0 €

Although we often think of undocumented persons as migrants or non-citizens, about one in seven people across the globe lack documents such as birth certificates, ID cards or passports to prove their legal identity, and thus their status as citizens in their own country. This gap between citizens with and without state-recognized documents is just as consequential as the distinction between citizens and non-citizens. Existing approaches portray the citizenship gap – the difference between legal status and the ability of citizens to document their claim to this status – as the apolitical by-product of deficiencies in governance. The proposed research project – CitizenGap – aims to change how scholars and policy-makers think about achieving one of the key targets of the United Nations’ Sustainable Development Goals “By 2030, provide legal identity for all, including birth registration” by developing a novel political understanding. The project establishes the citizenship gap as a field of social scientific research, and pursues two main questions: (1) How and why do states invest in civil registration? (2) How and why do citizens decide to obtain documents? To understand why millions of citizens are undocumented, it is crucial to remember that citizenship is not only a legal status, but first and foremost a political relationship between states and the populations they govern. CitizenGap advances a strategic theory that seriously considers the incentives of states and citizens in the politics of civil registration. Empirically, the project contributes a comprehensive, cross-national measure that captures the number and characteristics of undocumented citizens, including those at risk of having their citizenship status questioned. The project analyzes the origins and nature of the citizenship gap in India and Mexico with a mixed methods design, combining demographic and spatial (GIS) datasets with fieldwork, archival sources, interviews and focus groups

Mots-clés : birth registration,civil registration,legal identity,sustainable development goals,state capacity,subnational comparative research
Projet ERC : ADAMtx (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Alzheimer's disease (AD) is a heterogeneous disease in which multiple detrimental factors contribute to cognitive loss and disease escalation. Currently there are no effective therapies for AD. Targeting any single symptom of disease-escalating factor (e.g. amyloid beta, tau, neuroinflammation etc.), even if successful, is not sufficient to modify the disease, as seen in the multiple failures of recent phase-III clinical trials. Thus, there is a desperate need for new approaches for development of AD therapeutics, which will be more comprehensive and not etiology-specific. Using single cell genomic analysis of the immune system in AD mouse models, we discovered a novel microglia type, disease associated microglia (DAM), intrinsic immune cells of the brain that fight AD and neurodegenerative disease. There are several revolutionary aspects to our approach to modify AD course. Fundamentally, based on our unique DAM pathways and target discovery platform we will develop novel AD-immunotherapy for boosting the brain’s innate neuroprotective mechanisms that fight neurodegeneration in AD. Development of targets that boost DAM cells is a major activity of this PoC plan, and we are in different phases of development of several targets that increase DAM activity including advanced stages of the targets Trem2 and P2ry12. The first goal of this PoC grant is to develop and strengthen our IP around AD immunotherapy targets. The second goal is to design a viable and scalable business model with venture capital and establish a startup (ADAMtheraputics) that will translate our novel technology for effective AD-immunotherapy for Alzheimer patients. We believe that our unique approach of targeting the brain’s intrinsic protective immune cells, to boost their activity and numbers, will dramatically impact AD therapy.

Mots-clés : alzheimer,therapy,drug development,microglia