Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : SYMBeetle (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Johannes Gutenberg University Mainz — Pays : Allemagne — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 949532.45 €

To elucidate the key adaptations underlying evolutionary success remains one of the central challenges in evolution and ecology. However, rigorous experimental tests are usually hampered by the lack of replicate evolutionary events or the inability to manipulate a candidate trait of importance. SYMBeetle exploits the naturally replicated evolution of an experimentally tractable, symbiont-assisted key adaptation in beetles to understand its impact on niche expansion and diversification. Recent evidence indicates that beetles across at least seven different families associate with microbial symbionts that provision their host with tyrosine, an aromatic amino acid necessary for cuticle biosynthesis, hardening, and tanning. SYMBeetle addresses the hypothesis that the acquisition of tyrosine-supplementing microbes constituted a key innovation across phylogenetically distinct beetles that allowed them to expand into novel ecological niches, by relaxing the dependence on nitrogen-rich diets for successful formation of the rigid exoskeleton and protective front wings. Specifically, tyrosine supplementation may facilitate the transition to herbivory and allow for subsisting at very low ambient humidity, by facilitating the production of a thick cuticular barrier to desiccation. To test this, SYMBeetle will uniquely combine experimental manipulation of symbiotic associations to assess the symbionts’ contribution to cuticle biosynthesis and its fitness consequences (desiccation resistance and defense) with large-scale comparative approaches aimed at elucidating the taxonomic distribution, ecological contexts, and evolutionary origins of cuticle-supplementing symbioses. The results are expected to transform our understanding of microbes as important facilitators for the evolution of herbivory and the colonization of dry habitats in beetles, two factors of major relevance for the emergence of economically relevant insect pests of agricultural crops and stored products.
Projet ERC : EvoGenMed (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Max Delbrück Center for Molecular Medicine — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : MDC
Type d'entité : Recherche
Financement ERC de l'entité : 100000.0 €

To make for better diagnostics and safer applications of genomics we need a better understanding of our genome and how it functions. Until recently we thought we knew: intergenic sequence must be largely “junk” and mutations that, for example, affect genes but not the protein (synonymous mutations) must be effectively neutral. This degenerate genome view accords with the nearly-neutral theory’s prediction that selection will be weaker when populations are small. But is this all there is to it? I shall investigate two new interrelated perspectives on genome evolution. First, I suggest that to mitigate errors, owing to our high error rates, our genome can be under stronger, not weaker, selection. Second, that errors might be a source of evolutionary novelty. Error mitigation, my team has shown, often involves selection on seemingly innocuous mutations such as synonymous changes. Remarkably, we discovered that selection to ensure error-proof splicing is possibly more prevalent on synonymous mutations when populations are small, making seemingly innocuous mutations stronger candidates for human diseases. I shall provide the first test of the new error-proofing perspective through comparative genomic analysis on synonymous site evolution. To investigate error as a source of novelty I shall consider whether expression piggy-backing (expression of a gene affecting its neighbors) forces rewiring of gene networks. Importantly, I shall translate our new understanding to enable better diagnostics and improved therapeutics. I shall develop a much-needed computer package to identify candidate disease-causing synonymous changes. In addition, knowing how synonymous sites modulate splicing will allow me to design better intronless transgenes. Transgenes must also be inserted in genomic regions immune to piggy-backing. I will examine transposable element related piggy-backing to characterize “safe” sites for therapeutic gene insertion and mammalian transgenesis more generally.

Mots-clés : synonymous mutations,expression piggy backing,transgenes,nearly neutral theory,error mitigation
Projet ERC : EvoGenMed (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : University of Edinburgh — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 137500.0 €

To make for better diagnostics and safer applications of genomics we need a better understanding of our genome and how it functions. Until recently we thought we knew: intergenic sequence must be largely “junk” and mutations that, for example, affect genes but not the protein (synonymous mutations) must be effectively neutral. This degenerate genome view accords with the nearly-neutral theory’s prediction that selection will be weaker when populations are small. But is this all there is to it? I shall investigate two new interrelated perspectives on genome evolution. First, I suggest that to mitigate errors, owing to our high error rates, our genome can be under stronger, not weaker, selection. Second, that errors might be a source of evolutionary novelty. Error mitigation, my team has shown, often involves selection on seemingly innocuous mutations such as synonymous changes. Remarkably, we discovered that selection to ensure error-proof splicing is possibly more prevalent on synonymous mutations when populations are small, making seemingly innocuous mutations stronger candidates for human diseases. I shall provide the first test of the new error-proofing perspective through comparative genomic analysis on synonymous site evolution. To investigate error as a source of novelty I shall consider whether expression piggy-backing (expression of a gene affecting its neighbors) forces rewiring of gene networks. Importantly, I shall translate our new understanding to enable better diagnostics and improved therapeutics. I shall develop a much-needed computer package to identify candidate disease-causing synonymous changes. In addition, knowing how synonymous sites modulate splicing will allow me to design better intronless transgenes. Transgenes must also be inserted in genomic regions immune to piggy-backing. I will examine transposable element related piggy-backing to characterize “safe” sites for therapeutic gene insertion and mammalian transgenesis more generally.

Mots-clés : synonymous mutations,expression piggy backing,transgenes,nearly neutral theory,error mitigation
Projet ERC : DDREAMM (Horizon 2020, appel 2019, Synergy grants)
Entité participante : Austrian Academy of Sciences — Pays : Autriche — Rôle : PI
Acronyme de l'entité : OAW
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 0.0 €

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 : DDREAMM (Horizon 2020, appel 2019, Synergy grants)
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : CO-PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 4420150.0 €

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 : Trinity College Dublin — Pays : Irlande — Rôle : Partner
Acronyme de l'entité : TCD
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 181285.34 €

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 : RENEW (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
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 : 1999835.0 €

To this day, communications engineering has closely followed the seminal guidelines developed by Claude E. Shannon in 1948, which were mostly influenced by the telephone network of those days. The widespread use of mobile communications and the advent of machine-to-machine communications nowadays entail an exponential increase in data rates and the available models are no longer sufficient to design power-efficient, low-latency, high-speed communication systems. The overarching aim of RENEW is to further increase the data rates of the global telecommunication network while, at the same time, addressing its non-negligible environmental impact. By fundamentally revisiting the transceiver processing algorithms of the core parts of the communication network, RENEW has the potential to overcome the limitations of current design methodologies and to significantly reduce the complexity and energy consumption of the network. Capitalising on cutting-edge results in the fields of machine learning, reinforcement learning, optimisation techniques and neuromorphic computing, RENEW will reinvent the design of communication transmitters and receivers by introducing sparsely connected atomic neural blocks that realise highly parallelisable transceivers guaranteeing high throughputs with low energy consumption. RENEW will explore novel concepts for extremely energy efficient receivers based on spiking neural networks, promising efficiency gains by multiple orders of magnitude. The viability of the RENEW concepts will be demonstrated in applications of high relevance such as high-speed optical communication networks or low-power IoT applications. My industrial experience designing high-speed optical communications, together with my background in coding and communication theory as well as machine learning techniques will be an important enabler for the RENEW concept, which has a transformative potential as it will consequently yield novel energy efficient communication systems.

Mots-clés : optical fibre communications,energy efficient communications,error correction codes,coherent communications,machine learning for communications,deep learning
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 California System — Pays : Etats-Unis — Rôle : Partner
Acronyme de l'entité : UC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

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 : NiSAN (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : Bar-Ilan University — Pays : Israël — Rôle : PI
Acronyme de l'entité : BIU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 149566.0 €

To understand how the brain works, tools need to be developed to allow the investigation of interactions between individual neurons. Towards this goal, We developed voltage sensing nanoparticles (vsNPs) in the shape of nanorods (vsNRs) that self-insert into the cell membrane and could optically record, non-invasively, action potentials (APs) at the single-particle and nanoscale level, at multiple sites, in a large field-of-view. The proposed nanosensors have unique advantages not offered by other methods: much larger voltage sensitivity, high brightness, and hence single-particle voltage sensitivity, large spectral shift , fast temporal response, minimal photobleaching, large two-photon excitation cross sections, excellent performance in the NIR, and compatibility with lifetime imaging. In this PoC proposal we seek to convert the NVS program from mainly “R” in R&D effort into “D” effort which will allow for IP protection, commercialization, dissemination, and therefore the ‘democratization’ of the technology to the large community of neuroscientists. In order to convert our achievement to commercially viable reagents business for the neuroscience community via the PoC program, we will (i) identify leading applications in neuroscience and brain research, (ii) improve current technology to meet the applications demands by fine tuning the control over size and shape of the particle and testing various types of coating, testing insertion into different lipid compositions in bilayers and cells, and by testing non-specific internalization, (iii) improve the stability and performance reproducibility of the sensors, (iv) develop methods for upscaling the synthesis of these NPs, (v) and formulate GLP protocols required for commercialization. Upon achievement of these goals, we will obtain a versatile, stable, multipurpose, novel tool to be implemented in neuroscience.

Mots-clés : electrophysiology,neurobiology,single molecule spectroscopy,physical chemistry,analytical chemistry,method development in chemistry,optical recording,bioelectronics,electroceuticals
Projet ERC : GRACEFUL (Horizon 2020, appel 2019, Synergy grants)
Entité participante : Centre national d'études spatiales — Pays : France — Rôle : PI
Acronyme de l'entité : CNES
Type d'entité : Recherche
Financement ERC de l'entité : 1040045.0 €

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