Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : ALTER-brain (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Spanish National Cancer Research Centre — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CNIO
Type d'entité : Recherche
Financement ERC de l'entité : 1897437.0 €

Organ colonization is the most inefficient step of metastasis. However, once a few cancer cells manage to re-initiate their growth in the brain, the initial naïve microenvironment, which was not favouring and even actively limiting the number of potential metastasis initiating cells, is slowly rewired into a different ecosystem with pro-metastatic properties. In this project (ALTER-brain), we will study the biology of microenvironment reprogramming to explore innovative ways of treating metastasis. Microenvironment reprogramming relies on altered molecular patterns that emerge in specific brain cell types simultaneously to the outgrowth of metastases. Dissecting the biology of these emerging patterns and their functional consequences could provide the basis to prevent metastasis but also to treat advances lesions. A key objective of ALTER-brain is the identification of newly established functional networks among previously non-connected components of the microenvironment that are critical to nurture tumour growth. This research proposal focuses on metastasis in the brain given its rising incidence, poor therapeutic options and short survival rates upon diagnosis. ALTER-brain will use novel (i.e. spontaneous metastasis) and clinically relevant (i.e. relapse after therapy) experimental mouse models of brain metastasis combined with genetically engineered mice in which we will target specific components of the microenvironment. In addition, we will apply novel lineage tracing technologies to understand the origin and emerging heterogeneity of the reprogrammed microenvironment. Given the clinical relevance of our research, human brain metastasis provided by our clinical network will be used to validate key findings. ALTER-brain will identify key principles underlying the unknown biology of the brain under a specific pathological pressure that might be translated to other highly prevalent disorders affecting this organ in the future.

Mots-clés : metastasis,microenvironment,brain,astrocytes,innate immune system,acquired immune system,experimental therapy,endothelial cells
Projet ERC : META-STRESS (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : University of Helsinki — Pays : Finlande — Rôle : PI
Acronyme de l'entité : UH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1494882.5 €

Organisms in the wild are constantly challenged by environmental variation in e.g. resource quality. The goal of this project is to move beyond laboratory experiments to understand the mechanisms that allow organisms in the wild to cope with environmental stress. Understanding the responses and mechanisms operating in wild populations is critical for assessing the eco-evolutionary consequences of environmental stress. The large metapopulation of the Glanville fritillary butterfly gives me a unique opportunity to study processes operating from genes within individuals all the way to metapopulation-level dynamics. I will use individuals sampled from families from specific local populations with known ecological background (based on > 20 years of data) to experimentally test the influence of environmental stress on life-history variation. I will combine these experiments with simultaneous life-history assessments on the siblings remaining in the wild, thus effectively coupling laboratory and field-based studies. I will integrate the ecological studies with molecular approaches to unravel the significance of different mechanisms – candidate genes, epigenetic inheritance and intestinal microbial communities – potentially influencing individual responses to environmental challenges. I will focus on the influence of host plant quality as an environmental stressor, which is known to greatly influence life histories in many organisms, and which can be manipulated in the laboratory and assessed in the wild. The proposed research has potential for groundbreaking results in evolutionary ecology, as the results will increase our understanding of 1) how individual responses to unfavorable environmental conditions and the underlying mechanisms vary within and among local populations in a spatially and temporally heterogeneous environment, and 2) how the consequent life-history variation influences the ecological and microevolutionary dynamics of wild populations.

Mots-clés : life history,metapopulation,environmental stress,conservation
Projet ERC : EVO-MEIO (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
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 : 750793.25 €

Organisms rely on conserved cellular “house-keeping” processes for survival and fertility, but many of these can be upset by common environmental or cellular stresses. What happens if such a challenge becomes more than transient? Meiosis is a well-suited model for understanding how a constrained multiprotein process can evolve; it is biochemically well characterized, critical for fertility in sexual eukaryotes, and its core structures and functions are conserved across kingdoms. Yet proteins that orchestrate meiosis often have high primary sequence divergence among taxa and in some cases have undergone selective sweeps. We hypothesize this pattern reflects a need to repeatedly retune meiotic structures to new conditions over evolutionary time. Environment and genome architecture can both affect meiosis, but a common and particularly potent challenge is whole genome duplication (WGD), which has occurred in most major eukaryotic lineages. But WGD doubles the number of copies of each homolog present, and this can lead to formation of multivalent chromosome associations in meiosis, which can cause meiotic instability and low fertility. Nevertheless, many fertile and meiotically stable polyploids exist, showing that evolution can overcome this challenge. Here we will study how meiotic stability evolved in autopolyploid Arabidopsis arenosa. We previously showed selection acted on eight structural meiosis proteins and hypothesize these co-evolved as an “adaptive module” to prevent multivalent formation by reducing genome-wide crossover rates. This multidisciplinary research programme melds cytological, molecular, genetic, and genomic approaches to discover how meiosis functionally evolved before and after WGD. This work will provide novel insights into how a functionally constrained multiprotein process can evolve in response to challenges, and by providing understanding of crossover rate evolution and polyploid stabilization, is also relevant to rational crop improvement.

Mots-clés : polyploidy,adaptation,meiosis
Projet ERC : FunctionalP4 (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Regensburg — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1955846.25 €

Organophosphorus compounds are an important and industrially relevant class of molecules with numerous uses, e.g. as reagents in organic synthesis, ligands in catalytically active metal complexes, and in pest control. State-of-the-art synthesis methods for all these valuable and useful compounds rely on an atom inefficient and hazardous multi-step procedure involving the oxidation of white phosphorus (P4) with toxic chlorine gas. Less wasteful and more environmentally benign methods are highly desirable, but transformations of white phosphorus directly into organophosphorus compounds are hardly developed. This project explores new methods for the activation and functionalization of white phosphorus. The metal-mediated stepwise transformation of P4 into organophosphorus compounds is a key objective. Novel transition metal compounds are designed and synthesized, which can generate reactive phosphorus units. The concept of heterobimetallic P4 activation, where two electronically different metal complexes interact with P4 cooperatively, is introduced for this purpose. Reactions of the phosphorus fragments in these new, reactive complexes with electrophiles will produce novel, fundamentally interesting organophosphorus compounds avoiding chlorinated intermediates. Catalytic methods for P4 functionalization are currently unknown, and developing such methods using transition metal and photoredox catalysts is an additional objective of this proposal. By providing novel synthetically useful and even catalytic procedures for converting P4 into organophosphorus compounds, this project will significantly contribute to the development of phosphorus chemistry and more sustainable synthesis methods.

Mots-clés : phosphorus,transition metal compounds,inorganic chemistry,organometallic chemistry
Projet ERC : QUCUBE (Horizon 2020, appel 2018, Synergy grants)
Entité participante : Commissariat à l’énergie atomique et aux énergies alternatives — Pays : France — Rôle : CO-PI
Acronyme de l'entité : CEA
Type d'entité : Recherche
Financement ERC de l'entité : 10980316.25 €

Originally conceived to describe the microscopic world of atoms and elementary particles, the theory of quantum mechanics has eventually served to predict macroscopic phenomena, e.g. the electrical and optical properties of semiconductors, resulting a wide range of technological applications that have changed our way of living. Foundational properties like quantum superposition and entanglement, however, have remained essentially unexploited. Their use may allow achieving computational powers inaccessible to classical digital computers, opening unprecedented opportunities. In a quantum computer, the elementary bits of information are encoded onto two-level quantum systems called qubits. Since qubits interact with the uncontrolled degrees of freedom of their environment, the evolution of their quantum states can become quickly unpredictable, leading to a reduced qubit fidelity. In topological quantum computing schemes, e.g. the surface code, the reduced fidelity is compensated by using decoherence-free logical qubits consisting of a large number (~103) of entangled physical qubits. As a result, a useful quantum processor should host at least millions of qubits. Although dauntingly large, this number is still small as compared to the number of transistors in a modern silicon microprocessors. QuCube leverages industrial-level silicon technology to realize a quantum processor containing hundreds of spin qubits confined to a two-dimensional array of electrostatically defined silicon quantum dots. To face the challenge of addressing the qubits individually, we use a three-dimensional architecture purposely designed to accommodate, on separated planes, the charge sensing devices necessary for qubit readout, and the metal gate lines for the electrical control and measurement. The gate lines are operated according to a multiplexing principle, enabling a scalable wiring layout. We shall implement fault-tolerant logical qubits and quantum simulations of complex Hamiltonians

Mots-clés : nanoelectronics,quantum computing,scalability,silicon,cmos devices  complementary metal oxide semiconductors devices
Projet ERC : FAtoUnFRAGILITY (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
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 : 1462383.0 €

Originally described by cytogeneticists, common fragile sites (CFSs) are chromosomal regions known for their susceptibility to break and rearrange aberrantly, thus altering the expression of genes located therein. CFS instability is associated with tumor development and pathogenic copy number variations. Recent advances have significantly contributed to dissect the molecular bases of CFS instability, yet a unifying model for their unique breakage propensity has not been determined. Fanconi anemia (FA) is a chromosomal instability syndrome featuring congenital abnormalities, bone marrow failure and cancer predisposition, characterized by an increased CFS fragility. FA is thus an ideal model to understand the mechanisms underpinning CFS instability and the mechanistic link between CFS instability and the pathogenesis of disease phenotypes. I propose to use FA cellular models to examine the molecular events leading to CFS instability, and FA mouse models to investigate the consequences of deletions, amplifications or rearrangements involving CFSs on the expression of genes regulating critical signal transduction pathways involved in cell survival, proliferation, and differentiation. Exploring these mechanisms can lead to the development of chemopreventive or therapeutic strategies targeting aberrant gene expression or pathological pathways.
Projet ERC : SynapseBuild (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Forschungsverbund Berlin — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : FVB
Type d'entité : Recherche
Financement ERC de l'entité : 2496875.0 €

Our ability to move, to process sensory information or to form, store and retrieve memories crucially depends on the function of neuronal synapses. Synapses comprise a presynaptic compartment harboring the machinery for neurotransmitter release and an associated postsynaptic compartment that processes the neurotransmitter signal. During decades of research we have acquired a wealth of knowledge regarding the mechanisms of neurotransmitter release and information processing in the postsynaptic compartment. In great contrast, we know surprisingly little about the pathways that direct the formation, transport, and assembly of the complex molecular machines that make up a functional presynapse. In particular, it is unclear where and how synaptic vesicle (SV) precursors are formed in the neuronal cell body, in which form they are transported along the axon, and which maturation steps occur to allow their assembly into functional units for neurotransmitter release. How cytoplasmically synthesized presynaptic active zone (AZ) proteins that organize SV release sites are transported and assembled is equally unclear. Here, we combine genome engineering in stem cell-derived neurons and genetically altered mice with proteomic, high-resolution imaging and systems biology approaches to identify the origin and composition of SV and AZ precursors, dissect the mechanisms of their axonal transport and integration into developing synapses and unravel the pathway that controls axonal transport and presynaptic assembly of newly made SV and AZ proteins to set synaptic weight. Our high risk/ high gain studies will yield groundbreaking insights into the mechanisms that mediate the formation, maintenance, and dynamic remodeling of the presynaptic compartment during development and thereby fill a crucial knowledge gap in neuroscience. Furthermore, they may pave the way for the future development of therapeutics to cure nerve injury or neurological disorders linked to synapse dysfunction.

Mots-clés : neurotransmission,synapse development,presynaptic compartment,synaptic vesicle,active zone,axonal,transport,biogenesis,human neurons,high resolution imaging
Projet ERC : POPP (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : University of Konstanz — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Our advanced ERC grant MemoTV (Memories of Trauma and Violence) confirmed and expanded upon previous research demonstrating that early trauma history and future violent behaviour are closely associated. However, public health and community violence prevention programs continue to overlook the need to address underlying trauma among perpetrators. MemoTV uncovered that aggressive behavior is fuelled by two cycles of violence, one traumatic/aversive and one appetitive/appealing. Based on this knowledge, a treatment (FORNET) has been developed to cure related psychopathology and alter future dynamics of individual development. Substantial success in the rehabilitation of youth offenders has been shown in controlled trials, including street children, former child soldiers and youth gang members of Africa. We now want to prove for the European context that a system can be put into practice that supports unaccompanied minor refugees with trauma and delinquency experiences. The organizational structure will follow the proposal that we elaborated in the report of the German National Academy whereby peer counselors – individuals with their own history of migration – assist traumatized refugees. Through POPP (Putting Offence Prevention into Practice), we will prove that it is possible to support an increasing number of youth with a history of trauma and aggression back to mental and social well-being.

Mots-clés : traumatic stress,refugee,youth,violence,integration,psychotherapy,counseling
Projet ERC : RESHUFFLE (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : KU Leuven — Pays : Belgique — Rôle : PI
Acronyme de l'entité : KUL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1464187.0 €

Our continent is being shaken by a set of major challenges ranging from economic to security, refugee and rule of law crises. These events place unprecedented pressure on the institutional framework designed to hold Europe together since the second world war. The EU has emerged as the key player whenever the most fundamental rights of individuals are at stake. This is somewhat surprising. Since the 1950s, scientists have understood the European edifice as being based, on the one hand, on the Council of Europe designed to protect European values and fundamental rights in particular; and, on the other, on the EU intended to advance European (economic) integration. Therefore, it is the Council of Europe, an international organization distinct from the EU, that was initially placed at the forefront of fundamental rights protection. Yet, the EU is now taking the lead on setting fundamental rights standards. Benefits may be considerable where the EU offers strong institutional support. There may however also be a profound mismatch between the new function of the EU and its constitutional design. For instance, it may be inappropriate to address religious discrimination in employment – such as regulating the conditions for headscarf bans - through the same harmonization tools ensuring the free movement of goods. Are new concepts and legal tools needed to ensure trust in the EU system? The principal investigator, an EU constitutional and fundamental rights expert, will critically assess the shift in the nature of the EU’s contribution to European fundamental rights law with a view to better defining the new function of the EU in the field and making recommendations to improve its ability to perform such a function. For that purpose, she will draw on three aspects: legal research highlighting the main features of this stronger decision-making powers of the EU; theory of law informing the implications of the EU’s new quest for European values; and political and social science investigating the impact on stakeholders’ strategies.

Mots-clés : european union,fundamental rights,pillar of social rights,essence of rights,strategic litigation
Projet ERC : EXACTC (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
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 : 1922232.0 €

Our current fundamental understanding of the world is through the Standard Model, which is based on gauge theory. But conventional computational tools are either bound to the weakly coupled regime or have rather limited precision. This project is built upon the unique and novel fundamental structure I found, called the Quantum Spectral Curve. It is based on integrability, and allows one to get exact results in an important class of gauge theories at finite values of the coupling. Using the Quantum Spectral Curve I computed the quark–antiquark potential and found the spectrum of dimensions of all local operators in the planar N=4 Super-Yang-Mills theory. With this formulation, I also obtained new predictions for the high energy scattering amplitudes in QCD. This proposal explains how to use the Quantum Spectral Curve, in combination with the powerful method of separation of variables in integrable systems, to compute all correlation functions. This would imply the solution of a Quantum Field Theory in 4D for the first time. Using integrability in gauge theory has proven to be greatly successful, but equally it requires a broad range of skills, expertise, and human resources. My track record of directing successful research teams, combined with my world-leading expertise of the Quantum Spectral Curve, places me perfectly to deliver this groundbreaking result.

Mots-clés : quantum field theories,integrable systems,gauge,gravity duality