Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : DDREAMM (Horizon 2020, appel 2019, Synergy grants)
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3463175.0 €

To monitor and protect their genomes, eukaryotic cells have evolved sophisticated DNA-damage response (DDR) systems that comprise DNA repair and DNA-damage signaling processes. DDR deficiencies are associated with diverse human disorders, ranging from aggressive hereditary and sporadic cancers to inherited genetic diseases. The impact of DNA repair has also recently been harnessed to treat diseases through “synthetic lethal” cancer treatments and CRISPR-Cas genome editing. However, the fundamental interactions between DDR pathways that underpin such therapeutic opportunities are still not well understood. Furthermore, we are only just beginning to understand how suppressive functional interactions (so-called “synthetic viability”) can lead to resistance to DDR-targeting therapeutics. Our proposed research will address these important issues by using cutting-edge technologies in gene editing and chemical biology, and by taking a multidisciplinary approach to create deeply integrated genetic and physical maps of DDR pathways and interactions in many human cell types. Next-generation CRISPR-Cas transcriptional genome-wide approaches will be used to uncover hypo- and hyper-morph alleles that affect cellular sensitivity to DNA-damaging agents and DDR-enzyme inhibitors, thus providing insights into DDR events and explaining human DDR-deficiency phenotypes. Mass spectrometry and in-depth mechanistic studies will establish physical interaction networks within the genetic framework and reveal the signaling logic that underpins DDR outcomes and vulnerabilities. With chemical-genetic approaches, we will develop small molecule tools to precisely interrogate DDR pathways and that could lead to new therapeutic agents. In sum, our work should provide major insights into human genome surveillance in multiple cell types, yield powerful tools to precisely control DNA repair outcomes, and speed the development of new therapies for cancer and other diseases.

Mots-clés : crispr cas,genetic screening,physical interaction,drug discovery,synthetic lethality,synthetic resistance,dna damage and repair
Projet ERC : STRATIFY (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Nottingham — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 283214.86 €

To reduce the burden of mental disorders it is a formidable aim to identify widely applicable disease markers based on neural processes, which predict psychopathology and allow for targeted interventions. We will generate a neurobehavioural framework for stratification of psychopathology by characterising links between network properties of brain function and structure and reinforcement–related behaviours, which are fundamental components of some of the most prevalent mental disorders, major depression, alcohol use disorder and ADHD. We will assess if network configurations define subtypes within and if they correspond to comorbidity across these diagnoses. We will identify discriminative data modalities and characterize predictors of future psychopathology. To identify specific neurobehavioural clusters we will carry out precision phenotyping of 900 patients with major depression, ADHD and alcohol use disorders and 300 controls, which we will investigate with innovative deep machine learning methods derived from artifical intelligence research. Development of these methods will optimize exploitation of a wide range of assessment modalities, including functional and structural neuroimaging, cognitive, emotional as well as environmental measures. The neurobehavioural clusters resulting from this analysis will be validated in a longitudinal population-based imaging genomics cohort, the IMAGEN sample of over 2000 participants spanning the period from adolescence to adulthood and integrated with information generated from genomic and imaging-genomic meta-analyses of >300.000 individuals. By targeting specific neural processes the resulting stratification markers will serve as paradigmatic examples for a diagnostic classification, which is based upon quantifiable neurobiological measures, thus enabling targetted early intervention, identification of novel pharmaceutical targets and the establishment of neurobehaviourally informed endpoints for clinical trials.
Projet ERC : hybridFRET (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : Heinrich Heine University Düsseldorf — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : HHU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499457.5 €

To understand and modulate biological processes, we need their spatiotemporal molecular models. In this project we propose to build these models by a holistic approach. The recent methodological and technical advances in fluorescence spectroscopy and microscopy as well as in multi-scale modelling of complex biochemical systems set the stage to tackle cross-fertilizing challenges in biophysics, biochemistry and cell biology. The applicant proposes to develop a novel integrative platform for a Molecular Fluorescence Microscope (MFM) to achieve ultimate resolution in space (sub-nanometer) and time (picoseconds) for characterizing structure and dynamics of proteins. MFM will combine Multi-parameter Fluorescence Detection with Computational Microscopy (molecular dynamics and coarse grained simulations) in a hybrid approach, first, to derive a complete molecular description of all fluorescence properties of the tailored dyes in proteins (objectives 1 and 2) and, second, to utilize this information in simulations to report on the protein properties (objective 3). In this hybrid approach high precision FRET measurements are the core experimental technique (hybridFRET). The MFM will allow us to tackle the central biophysical question of how intra- and intermolecular domain interactions modulate proteins' overall structure, dynamics, and thus ultimately function (objective 4). In this proposal we will apply MFM to two prototypic proteins of significant medical relevance. The combination with Multi-parameter Fluorescence Image Spectroscopy will exploit the ultimate resolution of the MFM for molecular protein imaging in live cells. To follow and ultimately understand biological processes, we need their spatiotemporal models of the integrative fluorescence spectroscopy platform. Until now, no holistic use of fluorescence spectroscopy for structural modelling of proteins has been reported.

Mots-clés : fluorescence microscopy,fret
Projet ERC : NVS (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : University of Göttingen — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : GAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 175000.0 €

To understand how the brain works, tools need to be developed that will allow neuroscientists to investigate how interactions between individual neurons lead to emergent networks. Towards this goal, we will develop targetable voltage sensing nanorods that self-insert into the cell membrane and optically and non-invasively record action potentials at the single particle and nanoscale level, at multiple sites and across a large field-of-view. In semiconductors, absorption and emission band edges are modulated by an external electric field, even more so when optically excited electron-hole pairs are confined, giving rise to the quantum confined Stark effect. The physical origin of this effect is in the separation of photoexcited charges, creating a dipole that opposes the external field. The proposed sensors will optically record action potential with unique advantages not offered by other methods: much larger voltage sensitivity, high brightness, and hence single-particle voltage sensitivity, large spectral shift (affording noise-immune ratiometric measurements), fast temporal response, minimal photobleaching, large Stokes shifts, large two-photon excitation cross sections, excellent performance in the NIR, and compatibility with lifetime imaging. The proposed sensors could afford, for example, the recording of pre- and post-synaptic membrane potentials, sub-threshold events, ultrafast spiking, individual ion channel activity, or a release of ions from single Ca+2 stores. In addition, deep tissue imaging could be afforded by two photon microscopy and far-field non-linear temporal focusing combined with lifetime imaging. Here we seek to optimize all aspects of the sensors’ synthesis, functionalization, delivery, targeting and detection, in order to provide neuroscientists and physiologists a viable and user-friendly technology that will be generally useful for the study of action potential signals in the brain and in healthy or diseased heart and muscle tissues.

Mots-clés : biophysics,electrophysiology,neurobiology,single molecule spectroscopy,physical chemistry,analytical chemistry,method development in chemistry,physical chemistry of biological systems
Projet ERC : GRACEFUL (Horizon 2020, appel 2019, Synergy grants)
Entité participante : Royal Observatory of Belgium — Pays : Belgique — Rôle : CO-PI
Type d'entité : Recherche
Financement ERC de l'entité : 2890515.0 €

To understand the processes involved in the deep interior of the Earth and explaining its evolution, in particular the dynamics of the Earth’s fluid iron-rich outer core, only indirect satellite and ground observations are available. They each provide invaluable information about the core flow but are incomplete on their own: - The time dependent magnetic field, originating mainly within the core, can be used to infer the motions of the fluid at the top of the core on decadal and subdecadal time scales. - The time dependent gravity field variations that reflect changes in the mass distribution within the Earth and at its surface occur on a broad range of time scales. Decadal and interannual variations include the signature of the flow inside the core, though they are largely dominated by surface contributions related to the global water cycle and climate-driven land ice loss. - Earth rotation changes (or variations in the length of the day) also occur on these timescales, and are largely related to the core fluid motions through exchange of angular momentum between the core and the mantle. The GRACEFUL project will go beyond the potential of individual satellite and ground observations and will combine the information about the core deduced from the gravity field, from the magnetic field and from the Earth rotation in synergy, in order to examine in unprecedented depth the dynamical processes occurring inside the core and at the core-mantle boundary. We will develop cutting-edge algorithms to process observational data and use up-to-date numerical models of the core flow to infer its dynamics. This interdisciplinary approach will challenge our current understanding of the core dynamics and provide a step change in our understanding of the deep Earth’s interior. The pioneering approach of GRACEFUL will provide an innovative template to obtain totally novel information about the dynamic processes inside the fluid core and core-mantle boundary of the Earth.

Mots-clés : earth rotation,earth gravity,earth magnetic field,fluid core motions
Projet ERC : GRACEFUL (Horizon 2020, appel 2019, Synergy grants)
Entité participante : Magellium — Pays : France — Rôle : PI
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 664514.0 €

To understand the processes involved in the deep interior of the Earth and explaining its evolution, in particular the dynamics of the Earth’s fluid iron-rich outer core, only indirect satellite and ground observations are available. They each provide invaluable information about the core flow but are incomplete on their own: - The time dependent magnetic field, originating mainly within the core, can be used to infer the motions of the fluid at the top of the core on decadal and subdecadal time scales. - The time dependent gravity field variations that reflect changes in the mass distribution within the Earth and at its surface occur on a broad range of time scales. Decadal and interannual variations include the signature of the flow inside the core, though they are largely dominated by surface contributions related to the global water cycle and climate-driven land ice loss. - Earth rotation changes (or variations in the length of the day) also occur on these timescales, and are largely related to the core fluid motions through exchange of angular momentum between the core and the mantle. The GRACEFUL project will go beyond the potential of individual satellite and ground observations and will combine the information about the core deduced from the gravity field, from the magnetic field and from the Earth rotation in synergy, in order to examine in unprecedented depth the dynamical processes occurring inside the core and at the core-mantle boundary. We will develop cutting-edge algorithms to process observational data and use up-to-date numerical models of the core flow to infer its dynamics. This interdisciplinary approach will challenge our current understanding of the core dynamics and provide a step change in our understanding of the deep Earth’s interior. The pioneering approach of GRACEFUL will provide an innovative template to obtain totally novel information about the dynamic processes inside the fluid core and core-mantle boundary of the Earth.

Mots-clés : earth rotation,earth gravity,earth magnetic field,fluid core motions
Projet ERC : ExELang (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
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 : 2007023.0 €

To what extent does experience affect child language acquisition? Answering this is crucial for our understanding of human cognition, but current evidence is insufficient because causal links between experience and outcomes cannot be established with typical approaches. We will study how the speech infants hear affects their learning of the sounds and structures of their native language, as represented in the speech the same infants produce, using an innovative and ecological technique: Audio-recordings collected with a recorder worn by the child throughout a normal day. Fifteen large-scale corpora will be combined, totaling over 25,000h of audio, collected from over 1,400 infants, living in rural and urban sites in every peopled continent, and learning a wide variety of mostly unrelated languages. We will develop cutting-edge machine learning algorithms to automatically analyze these long, messy, and multilingual recordings. This will yield measures representing infants' experiences (the speech addressed to them, and the speech they overhear) as well as how advanced their own vocalizations are. A subset of data come from Randomized Control Trials (RCTs) where treatment groups have received behavioral interventions aimed at increasing the quantity of speech infants are addressed. We aim to establish to what extent speech addressed to the infants and overheard speech affect their development by triangulating analyses of variation across individuals, cultures, and treatment-control contrasts. In parallel, we will use a reverse-engineering approach to assess the theoretically-predicted effects of experience. A variety of learning mechanisms will be implemented in unsupervised learning systems which take as input audio like that heard by infants and produce as output "vocalizations". If a system yields the same experience-outcome curves found in the infants’ data, then those learning mechanisms plausibly resemble those used by infants.
Projet ERC : EXCHANGE (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : University of Minho — Pays : Portugal — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1352147.88 €

Today we are living in the “genetic age” of criminal investigation. There is a widespread cultural belief that DNA technology has the unrivalled capacity to identify authors of crimes. In light of this ideology, EU Law (Prüm Decision, 2008) obliges all Member States to create the conditions for the reciprocal automated searching and comparison of information on DNA data for the purpose of combating cross-border crime, terrorism and illegal immigration. Forensic geneticists play a crucial role in this scenario: they develop the techno-scientific procedures that enable DNA data to be shared across national boundaries. EXCHANGE aims to understand the close links between a highly specialised field of expert knowledge – forensic genetics – and surveillance in the EU. If the EU succeeds in this political project, about 10 million genetic profiles of identified individuals will be exchanged between agencies in all EU countries. This raises acute cultural, political and societal challenges. EXCHANGE aims to address these challenges by scrutinizing how forensic geneticists, within the context of the transnational exchange of DNA data in the EU, engage with the social values attributed to science – i.e. objectivity, truth – and the values of social control, citizenship and democracy. The expected outputs are: 1. To provide a general picture of the Prüm framework by conducting interviews with forensic geneticists in all EU countries; 2. To develop in-depth knowledge of forensic geneticists’ activities relating to Prüm using ethnographic observation and qualitative analysis of criminal cases; 3. To study countries with different local positionings in relation to Prüm by means of a comparative study involving Portugal, Germany, the Netherlands and the UK. EXCHANGE stimulates interdisciplinary dialogue between the social sciences and the forensic genetics. This research also tackles questions that are relevant to all the actors involved in criminal justice cooperation in the EU.

Mots-clés : social studies of forensic genetics,dna evidence,transnational exchange of dna data,surveillance,suspects,social control,citizenship and human rights,democracy,pr m decision
Projet ERC : PARQ (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer science and informatics
Entité participante : Institut national de recherche en sciences et technologies du numérique — Pays : France — Rôle : PI
Acronyme de l'entité : Inria
Type d'entité : Recherche
Financement ERC de l'entité : 2350040.0 €

Today's digital world creates many security and privacy issues. But cryptography, a pillar of cybersecurity, is facing two major challenges. The first challenge is the threat of quantum computers, fueled by massive investment worldwide. Shor showed that a quantum computer can break the most prevalent forms of public-key cryptography used every day by e-commerce and bitcoins. This threat is now taken seriously by governmental organizations: the NIST initiated in 2016 a process to standardize by 2024 public-key cryptographic algorithms resistant to quantum computers. The second challenge is new environments, such as big data, IoT, or crypto-currencies. Because classical cryptography no longer suffices for these applications, novel cryptographic schemes and functionalities have been developed, e.g. to allow anyone to compute with encrypted data. But these benefits come at the cost of security uncertainty: it requires more risky assumptions and makes it more difficult to select parameters with confidence. Worryingly, the past few years have seen several established cryptographic assumptions collapse. Lattices are mathematical objects which have emerged in the past twenty years as the key technique to respond to these challenges: the ongoing standardization of homomorphic encryption and the majority of the candidates to NIST's post-quantum standardization rely on the conjectured hardness of lattice problems. This proposal aims at readying lattice-based cryptography for real-world deployment, by protecting it against the most powerful adversaries, from ASIC farms to quantum computers. We will study the best parallel and quantum algorithms for lattice problems, and derive automated tools to select safe parameters. The proposal will use the renowned expertise of the PI in lattice algorithms and cryptanalysis to explore the quantum frontiers of cryptanalysis.

Mots-clés : lattices,public key cryptography,quantum algorithms,parallel algorithms
Projet ERC : NGBMI (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : Charité - Universitätsmedizin Berlin — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1498125.0 €

Today, five out of ten diseases worldwide resulting in long-term disability are related to the central nervous system. Due to the immense complexity and inter-individual variability of the human mind and brain there are still no effective and side effect free treatment options for many serious neuropsychiatric disorders, such as major depression, dementia or schizophrenia. Recent advancements in sensor technology and computational capacities resulted in the development of brain/neural-machine interfaces (B/NMIs) that translate electric, magnetic or metabolic brain activity into control signals of external devices, robots or machines. Moreover, novel transcranial magnetic and electric brain stimulation (TMS/TES) systems were developed allowing for direct modulation of brain activity. However, current B/NMIs are limited by the low information extraction rate constraining fluent direct brain-machine interaction. Furthermore, as simultaneous assessment of brain oscillations during TES was regarded unfeasible due to stimulation artefacts, current TES systems can only deliver “open-loop” stimulation unrelated to the underlying dynamic brain states resulting in highly variable TES effects. Building on the applicant’s previous work that includes pioneering work on in vivo assessment of brain oscillations during TES (Soekadar et al. 2013, Nature Communications) and full restoration of daily living activities after quadriplegia using a novel B/NMI hand exoskeleton (Soekadar et al. 2016, Science Robotics), the NGBMI project will overcome these limitations by merging both techniques. After developing the first real-time B/NMI-TES system allowing for effective modulation of brain functions and fluent direct brain-machine interaction, the system will be tested in persons with impaired brain function (e.g. depression, dementia or stroke). Finally, the B/NMI-TES paradigm will be implemented in a wireless and wearable EEG-based system that can be used in everyday life environments.

Mots-clés : closed loop transcranial electric stimulation  tes,neural substrates of the human mind,everyday life brain,neural machine interfaces