Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : CARBOCENTRE (Horizon 2020, appel 2020, Synergy grants)
Entité participante : University of Barcelona — Pays : Espagne — Rôle : PI
Acronyme de l'entité : UB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1984750.0 €

Enzymes that produce and degrade oligosaccharides and glycoconjugates are present in all kingdoms of life. The ability to visualize, modulate and understand these carbohydrate-active enzymes (CAZymes) therefore offers great potential for human health and sustainable industries. To provide a “disruptive” shift in our understanding, we adopt in this proposal a multidisciplinary approach combining structural biology, enzymology, computational chemistry, organic synthesis, and chemical biology, with major leaders in these fields part of our CARBOCENTRE Synergy Team. Three fundamental strands will specifically target and ‘capture’ glycoprocessing enzyme active sites. Biochemical and 3-D structural analyses will inform computational dissection of the reaction coordinate of key enzymes for human health and biotechnology processes. Building on our founding work on retaining glycosidases we will also target inverting glycosidases and glycosyltransferases. Following fundamental analyses, our probes will feed research in two major application domains of human health and biotechnology: 1. To provide visualization, diagnosis, and inhibitor assays and clinical lead compounds for enzymes in cancers and genetic diseases (lysosomal storage disorders). 2. To explore the natural diversity of CAZymes and to discover, quantify and optimize new enzymes for food and household applications and for biomass conversion to biofuels. In an iterative cycle, structural biology and enzymology (Davies, York), will inform, through structures of enzymes and enzyme-inhibitor complexes, theoretical and computational chemistry (Rovira, Barcelona), which in turn will guide the design and synthesis (Overkleeft, Leiden), of inhibitors and activity-based probes for ensuing chemical biology studies in the domains of biomedicine and biotechnology.

Mots-clés : carbohydrate active enzymes,activity based protein profiling,carbohydrate chemistry,enzymology,biofuels,computational design,glycobiology,glycochemistry
Projet ERC : CARBOCENTRE (Horizon 2020, appel 2020, Synergy grants)
Entité participante : University of York — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3303625.0 €

Enzymes that produce and degrade oligosaccharides and glycoconjugates are present in all kingdoms of life. The ability to visualize, modulate and understand these carbohydrate-active enzymes (CAZymes) therefore offers great potential for human health and sustainable industries. To provide a “disruptive” shift in our understanding, we adopt in this proposal a multidisciplinary approach combining structural biology, enzymology, computational chemistry, organic synthesis, and chemical biology, with major leaders in these fields part of our CARBOCENTRE Synergy Team. Three fundamental strands will specifically target and ‘capture’ glycoprocessing enzyme active sites. Biochemical and 3-D structural analyses will inform computational dissection of the reaction coordinate of key enzymes for human health and biotechnology processes. Building on our founding work on retaining glycosidases we will also target inverting glycosidases and glycosyltransferases. Following fundamental analyses, our probes will feed research in two major application domains of human health and biotechnology: 1. To provide visualization, diagnosis, and inhibitor assays and clinical lead compounds for enzymes in cancers and genetic diseases (lysosomal storage disorders). 2. To explore the natural diversity of CAZymes and to discover, quantify and optimize new enzymes for food and household applications and for biomass conversion to biofuels. In an iterative cycle, structural biology and enzymology (Davies, York), will inform, through structures of enzymes and enzyme-inhibitor complexes, theoretical and computational chemistry (Rovira, Barcelona), which in turn will guide the design and synthesis (Overkleeft, Leiden), of inhibitors and activity-based probes for ensuing chemical biology studies in the domains of biomedicine and biotechnology.

Mots-clés : carbohydrate active enzymes,activity based protein profiling,carbohydrate chemistry,enzymology,biofuels,computational design,glycobiology,glycochemistry
Projet ERC : EpigenomeProgramming (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
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 : 1281205.0 €

Epigenetic alterations can be detected in all cancers and in essentially every patient. Despite their prevalence, the concrete functional roles of these alterations are not well understood, for two reasons: First, cancer samples tend to carry many correlated epigenetic alterations, making it difficult to statistically distinguish relevant driver events from those that co-occur for other reasons. Second, we lack tools for targeted epigenome editing that could be used to validate biological function in perturbation and rescue experiments. The proposed project strives to overcome these limitations through experimental and bioinformatic methods development, with the ambition of making and breaking cancer cells in vitro by introducing defined sets of epigenetic alterations. We will focus on leukemia as our “model cancer” (given its low mutation rate, frequent defects in epigenetic regulators, and availability of excellent functional assays), but the concepts and methods are general. In Aim 1, we will generate epigenome profiles for a human knockout cell collection comprising 100 epigenetic regulators and use the data to functionally annotate thousands of epigenetic alterations observed in large cancer datasets. In Aim 2, we will develop an experimental toolbox for epigenome programming using epigenetic drugs, CRISPR-assisted recruitment of epigenetic modifiers for locus-specific editing, and cell-derived guide RNA libraries for epigenome copying. Finally, in Aim 3 we will explore epigenome programming (methods from Aim 2) of candidate driver events (predictions from Aim 1) with the ultimate goal of converting cancer cells into non-cancer cells and vice versa. In summary, this project will establish a broadly applicable methodology and toolbox for dissecting the functional roles of epigenetic alterations in cancer. Moreover, successful creation of a cancer that is driven purely by epigenetic alterations could challenge our understanding of cancer as a genetic disease.

Mots-clés : epigenomics,dna methylation,histone modifications
Projet ERC : Epiherigans (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : University of Lausanne — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UNIL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 7023.56 €

Epigenetic inheritance is the transmission of information, generally in the form of DNA methylation or post-translational modifications on histones that regulate the availability of underlying genetic information for transcription. RNA itself feeds back to contribute to histone modification. Sequence accessibility is both a matter of folding the chromatin fibre to alter access to recognition motifs, and the local concentration of factors needed for efficient transcriptional initiation, elongation, termination or mRNA stability. In heterochromatin we find a subset of regulatory factors in carefully balanced concentrations that are maintained in part by the segregation of active and inactive domains. Histone H3 K9 methylation is key to this compartmentation. C. elegans provides an ideal system in which to study chromatin-based gene repression. We have demonstrated that histone H3 K9 methylation is the essential signal for the sequestration of heterochromatin at the nuclear envelope in C. elegans. The recognition of H3K9me1/2/3 by an inner nuclear envelope-bound chromodomain protein, CEC-4, actively sequesters heterochromatin in embryos, and contributes redundantly in adult tissues. Epiherigans has the ambitious goal to determine definitively what targets H3K9 methylation, and identify its physiological roles. We will examine how this mark contributes to the epigenetic recognition of repeat vs non-repeat sequence, and mediates a stress-induced response to oxidative damage. We will examine the link between these and the spatial clustering of heterochromatic domains. Epiherigans will develop an integrated approach to identify in vivo the factors that distinguish repeats from non-repeats, self from non-self within genomes and will examine how H3K9me contributes to a persistent ROS or DNA damage stress response. It represents a crucial step towards understanding of how our genomes use heterochromatin to modulate, stabilize and transmit chromatin organization.
Projet ERC : Epiherigans (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Friedrich Miescher Institute — Pays : Suisse — Rôle : Partner
Acronyme de l'entité : FMI
Type d'entité : Recherche
Financement ERC de l'entité : 2492976.44 €

Epigenetic inheritance is the transmission of information, generally in the form of DNA methylation or post-translational modifications on histones that regulate the availability of underlying genetic information for transcription. RNA itself feeds back to contribute to histone modification. Sequence accessibility is both a matter of folding the chromatin fibre to alter access to recognition motifs, and the local concentration of factors needed for efficient transcriptional initiation, elongation, termination or mRNA stability. In heterochromatin we find a subset of regulatory factors in carefully balanced concentrations that are maintained in part by the segregation of active and inactive domains. Histone H3 K9 methylation is key to this compartmentation. C. elegans provides an ideal system in which to study chromatin-based gene repression. We have demonstrated that histone H3 K9 methylation is the essential signal for the sequestration of heterochromatin at the nuclear envelope in C. elegans. The recognition of H3K9me1/2/3 by an inner nuclear envelope-bound chromodomain protein, CEC-4, actively sequesters heterochromatin in embryos, and contributes redundantly in adult tissues. Epiherigans has the ambitious goal to determine definitively what targets H3K9 methylation, and identify its physiological roles. We will examine how this mark contributes to the epigenetic recognition of repeat vs non-repeat sequence, and mediates a stress-induced response to oxidative damage. We will examine the link between these and the spatial clustering of heterochromatic domains. Epiherigans will develop an integrated approach to identify in vivo the factors that distinguish repeats from non-repeats, self from non-self within genomes and will examine how H3K9me contributes to a persistent ROS or DNA damage stress response. It represents a crucial step towards understanding of how our genomes use heterochromatin to modulate, stabilize and transmit chromatin organization.
Projet ERC : DECAF (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Bielefeld University — Pays : Allemagne — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 421109.51 €

Epigenetics plays a fundamental role in the function and regulation of the genome. From an evolutionary viewpoint, a pressing question is whether epigenetic modifications are a source of adaptive variation. To answer this question substantial attention is being given to the epigenetic marks themselves, but surprisingly little is known about the evolutionary underpinnings of the genomic sites that anchor them. Using novel analytical and technical approaches, I want to address this fundamental knowledge gap. I will use the best understood epigenetic mark, DNA methylation, as a model and advance on recent findings in avian genome evolution, epigenetic inheritance and sequencing technology. This will enable me to pinpoint signatures of epigenetically driven adaptation. I have designed separate approaches at three different levels: (1) At the individual level, to identify stably methylated anchors in the avian germline with focus on a recently discovered germline-specific chromosome, (2) at the population level, to establish the selective forces acting on DNA methylation diversity in natural populations and (3) at the species level, to gain insight into how fast-mutating anchors of DNA methylation act as potential facilitators of species differentiation and barriers. Ultimately, by combining these three levels I will be able to pinpoint epigenetic anchors that are involved in molecular adaptation. The possible research outcomes will not only be valuable to evolutionary biologists and ecologists, but will also make fundamental contributions to molecular biology and possibly medical research, and will deepen our understanding of how epigenetic marks manifest themselves at the sequence level.

Mots-clés : adaptive evolution,dna methylation,speciation,gene flow,mutation rate variation,embryogenesis,bird genomics,whole genome sequencing,epigenetics
Projet ERC : NOSUDEP (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Imperial College London — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999999.0 €

Epilepsy is a neurological condition that affects approximately 1% of the population (or over 50 million people in the world). Europe alone is home to 6 million people that suffer from epilepsy with one new case every minute. In certain cases, healthy patients with epilepsy can die suddenly and unexpectedly. This is known as Sudden Unexpected Death in Epilepsy (SUDEP). SUDEP kills thousands of people in Europe every year. Unfortunately the mechanisms of SUDEP are not known, which makes it unpredictable Individuals with refractory tonic-clonic or complex-partial seizures are at the highest risk of SUDEP. These comprise approximately one third of the population affected by epilepsy, i.e. in the order of 2 million people in Europe. The focus of this research project is to carry out multidisciplinary research on wearable medical technologies with the ultimate aim of helping to protect epilepsy patients from SUDEP, by automatically and reliably alerting carers of physiologically dangerous indicators that are known to be precursors of it. These technologies will also have the potential to facilitate clinical research that is not possible with existing physiological monitoring systems. This could further current understanding of the mechanisms as well as individual risks factors of SUDEP, and consequently lead to specific disease management, treatment and prevention strategies targeted to the individual patient. Additionally, the research work carried out in this project will be beneficial in a number of clinical contexts, including but not limited to: diagnosis of paediatric and adult sleep apnoea (affects 2-10% of the population, but less than 20% are diagnosed in developed countries due to lack of in-clinic resources), early warning scoring in hospitals (i.e. 80% of patients in hospital), asthma (334 million people in the world, ), Chronic Obstructive Pulmonary Disease (64 million people in the world. 4th leading cause of death), and neonatal cot death (0.41% of babies)

Mots-clés : wearable technologies,low power electronics
Projet ERC : GALVANI (Horizon 2020, appel 2019, Synergy grants)
Entité participante : Neuroelectrics barcelona sl — Pays : Espagne — Rôle : PI
Acronyme de l'entité : Neuroelectrics
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 2928813.0 €

Epilepsy is a neurological disorder affecting 65 million people worldwide. Pharmacological treatments or surgery are ineffective in one third of the cases – 19 million people. Recent findings indicate that non-invasive brain transcranial current stimulation (tCS) is safe and of therapeutic promise in epilepsy. However, it is not yet indicated as a standard treatment due to major scientific limitations: unknown mechanisms of action, insufficient account for patient-specific factors, poor understanding of short- and long-term effects. Our ambition is to transform the care of a large fraction of patients living with drug-resistant epilepsies by solving a fundamental problem: to efficiently target and control large-scale epileptic brain networks with tCS-induced neuromodulatory weak electric fields. To proceed, GALVANI’s synergetic research strategy addresses four interdisciplinary challenges: (1) Unravel the intricate relationship between weak electric fields and their neurophysiological effects at the level of neurons, neuronal assemblies and networks; (2) Maximize their therapeutic effects by altering the neurodynamics of patient-specific epileptogenic networks; (3) Develop optimal personalized neuromodulation protocols for novel multichannel tCS technologies; (4) Test optimized protocols in a cohort of patients and objectively define potential responders. The required competences and resources are met in GALVANI, uniting the passion and background of three experts and their teams in biomathematics (computational neuroscience), biophysics (bioelectromagnetism) and medicine (epileptology). The project vision is that critical features of pathological networks can be effectively captured in a new generation of hybrid computational models developed for tailored therapy. The inflection point is to prevent epileptic seizures from a bottom-up mechanistic understanding and control of tCS effects. This will entail a paradigm shift in epileptic disorders and beyond.

Mots-clés : epilepsy,therapeutic neuromodulation,electric fields,bioelectromagnetism,neurophysiological,models,biophysical models,personalized models,signal processing,optimization,transcranial stimulation,clinical trial
Projet ERC : GALVANI (Horizon 2020, appel 2019, Synergy grants)
Entité participante : Aix-Marseille Université — Pays : France — Rôle : PI
Acronyme de l'entité : amU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2667231.75 €

Epilepsy is a neurological disorder affecting 65 million people worldwide. Pharmacological treatments or surgery are ineffective in one third of the cases – 19 million people. Recent findings indicate that non-invasive brain transcranial current stimulation (tCS) is safe and of therapeutic promise in epilepsy. However, it is not yet indicated as a standard treatment due to major scientific limitations: unknown mechanisms of action, insufficient account for patient-specific factors, poor understanding of short- and long-term effects. Our ambition is to transform the care of a large fraction of patients living with drug-resistant epilepsies by solving a fundamental problem: to efficiently target and control large-scale epileptic brain networks with tCS-induced neuromodulatory weak electric fields. To proceed, GALVANI’s synergetic research strategy addresses four interdisciplinary challenges: (1) Unravel the intricate relationship between weak electric fields and their neurophysiological effects at the level of neurons, neuronal assemblies and networks; (2) Maximize their therapeutic effects by altering the neurodynamics of patient-specific epileptogenic networks; (3) Develop optimal personalized neuromodulation protocols for novel multichannel tCS technologies; (4) Test optimized protocols in a cohort of patients and objectively define potential responders. The required competences and resources are met in GALVANI, uniting the passion and background of three experts and their teams in biomathematics (computational neuroscience), biophysics (bioelectromagnetism) and medicine (epileptology). The project vision is that critical features of pathological networks can be effectively captured in a new generation of hybrid computational models developed for tailored therapy. The inflection point is to prevent epileptic seizures from a bottom-up mechanistic understanding and control of tCS effects. This will entail a paradigm shift in epileptic disorders and beyond.

Mots-clés : epilepsy,therapeutic neuromodulation,electric fields,bioelectromagnetism,neurophysiological,models,biophysical models,personalized models,signal processing,optimization,transcranial stimulation,clinical trial
Projet ERC : STREAM (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : University of Glasgow — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 691919.67 €

Episodic memories are the essential building blocks of our identities. How the brain codes these memories such that we can access them minutes, days or even years later is still unknown. We tend to believe that the memories we bring back to mind are more or less precise "snapshots" of a past event. Reflecting this view, current neurocognitive studies focus on isolating static snapshots of past events in an individual's pattern of brain activity. This snapshot approach, however, ignores the reconstructive and dynamic nature of the retrieval process, necessarily limiting our understanding of human memory. The vision behind STREAM is to advance the field beyond its current state of the art by mapping the spatiotemporal dynamics of mnemonic reconstruction in the human brain. The research programme contains three work packages that support this vision at multiple levels of investigation, from combined electrophysiological and hemodynamic activity down to neuronal assembly firing patterns in the human hippocampus. These techniques are used in combination with paradigms that decompose memories into their constituent elements, and track the neural representations of these elements as they unfold in time and space when an event is reconstructed from memory. So far, it has been difficult to integrate information obtained by these various recording techniques. STREAM will use an innovative representational mapping approach that combines spatiotemporal information at the level of an individual's neural representational architecture. This approach enables us to directly map memory patterns emerging at a given time point onto a given brain region. If successful, STREAM will reveal the first comprehensive spatiotemporal map of memory retrieval, with the potential to cause a major shift in the field away from the currently dominant snapshot paradigm towards a time-resolved, reconstructive view of human memory.