Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : LIMBo (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Instituto de Biologia Experimental Tecnológica — Pays : Portugal — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 296325.0 €

Currently a big concern of our aging society is to efficiently delay the onset of neurodegenerative diseases which are progressively rising in incidence. The paradigm that a diet rich in the phenolics, prevalent e.g. in fruits, is beneficial to brain health has reached the public. However their mechanistic actions in brain functions remain to be seen, particularly since the nature of those acting in the brain remains overlooked. I wish to address this gap by identifying candidate compounds that can support development of effective strategies to delay neurodegeneration. Specifically, I will be analysing the potential of dietary phenolics in both prevention and treatment (i.e delay) of neuroinflammation – key process shared in neurodegenerative diseases. To break down the current indeterminate status of “cause vs effect”, my vision is to focus my research on metabolites derived from dietary phenolics that reach the brain. I will be investigating their effects in both established and unknown response pathways of microglia cells - the innate immune cells of the central nervous system, either alone or when communicating with other brain cells. Ultimately, to attain an integrated view of their effects I will establish nutrition trials in mice. LIMBo considers both pro- and anti- inflammatory processes to preliminary validate the action of any promising metabolite in prevention and/or therapeutics. LIMBo provides valuable scientific insights for future implementation of healthy brain diets. My group is in a unique position to address LIMBo objectives due to multidisciplinary expertise in organic synthesis, metabolomics and molecular and cellular biology, together with our previous data on novel neuroactive metabolites. LIMBo also creates far-reaching opportunities by generating knowledge that impacts our fundamental understanding on the diversity of phenolic metabolites and their specific influences in neuroinflammation and potential use as prodrugs.

Mots-clés : dietary phenolics,phenolics metabolism,brain,neuroinflammation
Projet ERC : DrugsInPregnancy (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Oslo — Pays : Norvège — Rôle : PI
Acronyme de l'entité : UiO
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499439.0 €

Currently, thousands of pregnant women in the EU and worldwide are being increasingly prescribed medications for which we do not have sufficient information on fetal safety. I hypothesize that our current understanding of safety pharmacology is oversimplified and that medication prescribed during pregnancy may play an unrecognized role in the development of neurodevelopmental disorders. In this research proposal we have the unique opportunity to use a large population-based birth cohort including over 100 000 mother-child pairs and biological data to study how medications may act on the offspring. This offers novel and innovative pharmaceutical insight into the safety of medications. By linking several nationwide registries (National Prescription Data Base, Norwegian Patient Registry, Medical Birth Registry) to a population-based birth cohort (n=108 000) we specifically aim to 1) estimate the effect of prenatal exposure to psychotropics and analgesics on neurodevelopment in young children using a range of methodological approaches to strengthen causal inference. With these data made available, we will 2) determine whether fetal exposure to specific medications results in epigenetic events (i.e. changes in DNA methylation) in the child, and 3) determine whether such changes increase the risks of neurodevelopmental disorders in childhood. The recent availability of large scale human data, possibility of register linkages and genome-wide mapping of DNA methylation at affordable costs makes this research proposal now possible. The size and richness of data including over hundred thousand pregnancies and existence of biological material makes this project unique. The final outcome will be fundamentally new knowledge about how medications affect the developing unborn child and will open up new horizons and opportunities for future research in a new field of “pharmaco-epigenetics” and enhance our understanding of origins of neurodevelopmental disorders.

Mots-clés : pharmaco epidemiology,medication use in pregnancy,psychotropics,analgesics,neurodevelopment
Projet ERC : PropRT (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer science and informatics
Entité participante : TU Dortmund University — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999055.0 €

Cyber-physical real-time systems are information processing systems that require both functional as well as timing correctness and have interactions with the physical world. Since time naturally progresses in the physical world, safe bounds of deterministic or probabilistic timing properties are required. PropRT will explore the possibilities to construct timing analysis for complex cyber-physical real-time systems from formal properties. The target properties should be modular so that safe and tight analysis as well as optimization can be performed (semi-)automatically. New, mathematical, modulable, and fundamental properties for property-based (schedulability) timing analyses and scheduling optimizations are needed to capture the pivotal properties of cyber-physical real-time systems, and thus enable mathematical and algorithmic research on the topic. Different flexibility and tradeoff options to achieve real-time guarantees should be provided in a modularized manner to enable tradeoffs between execution efficiency and timing predictability. The success of this project will provide a comprehensive view of the landscape of design, analysis, and optimization options for timing properties in cyber-physical real-time systems. Advanced optimization and analytical frameworks based on the formal properties of scheduling algorithms and schedulability analysis will serve as new ingredients for designing predictable cyber-physical systems, which will trigger a revolution of computer architectures, system modeling, communication mechanisms, and synchronization designs in the near future. The results will bring a new design process to further allow control designers and system integrators in cyber-physical real-time systems to jointly explore different configurations of controllers, computation, and communication parameters for designing timing predictable cyber-physical system applications.

Mots-clés : real time systems,worst case performance analysis
Projet ERC : PROCSYS (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
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 : 1266731.0 €

Cyber-physical systems (CPS) consist of computational elements monitoring and controlling physical entities. The main objective of the PROCSYS project is to propose a general framework for the design of programmable CPS that will allow engineers to develop advanced functionalities using a high-level programming language for specifying the behaviours of a CPS while abstracting the details of the physical dynamics. Controllers enforcing the specified behaviours will be generated from a high-level program using an automated model-based synthesis tool. Correctness of the controllers will be guaranteed by following the correct by construction synthesis paradigm through the use of symbolic control techniques: the continuous physical dynamics is abstracted by a symbolic model, which is a purely discrete dynamical system; an interface consisting of low-level controllers is designed such that the physical system and the symbolic model behaves identically; a high-level symbolic controller is then synthesized automatically from the high-level program and the symbolic model. We will develop a high-level programming language, based on the intuitive formalism of hybrid automata, which will enable to specify a rich set of behaviours while enabling the development of efficient controller synthesis algorithms. The project will also tackle the two main bottlenecks in the area of symbolic control, which will enable its use in challenging real-life applications. Firstly, scalability of symbolic control will be achieved by the computation of more compact symbolic models and by controller synthesis algorithms that require only partial exploration of the symbolic models. Secondly, robustness will be ensured at all levels of control by developing novel algorithms for the synthesis of robust interfaces and of symbolic controllers. The algorithms developed in the project will be implemented in a symbolic control toolbox, which will enable the use of our approach by systems engineers.

Mots-clés : hybrid dynamical systems,symbolic control
Projet ERC : DIGISMART (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Universidade Nova de Lisboa — Pays : Portugal — Rôle : PI
Acronyme de l'entité : NOVA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2871042.0 €

DIGISMART creates new avenues into two main areas: 1) processing nanomaterials/nanostructures applied to electronic devices by exploring a new digital multifunctional direct laser writing (LDW) method for in situ synthesis of small-sized nanomaterials/nanofilms micro-patterned growth by selective photothermal decomposition of semiconductors, dielectrics and conductors precursors and 2) provide simultaneously multifunction to single based metal oxide devices (like thin film transistors, the workhorses for large area electronics having electron, charge and color modulation), as the basic unit to promote systems’ integration by exploring the use of new advanced materials with unique multi-functionalities using low cost process solutions. This new fabrication process will be very useful for low-cost, eco-friendly, and efficient fabrication of nanostructures and thin films-integrated microelectronic devices due to its low-power, simple setup as well as excellent reliability. This new and disruptive concept will be achieved with low cost and non-toxic materials (new metal oxides, MO semiconductors, conductors, dielectrics and electrochromics free of In and Ga) associated to a low cost process multifunctional platform technology (ALL-IN-ONE TOOL) well supported by high-resolution nano-characterization techniques. With DIGISMART new and unexplored materials will be produced as well as to boost the original properties of conventional materials in order to contribute to the needs for low cost and flexible electronics. If we succeed to embed some level of intelligence in every object, this would change electronics and it would change society, ranging from embedded window displays to a wide range of biomedical electronics, just to mention a few and this is what the Internet of Things is looking for.

Mots-clés : thin films,nanomaterials
Projet ERC : GENECARE (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
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 : 1754552.0 €

DNA double-strand breaks (DSBs) are toxic lesions, holding the potential to generate mutations, copy number alterations and translocations. Beyond programmed DSBs induced during meiosis and antibody repertoire generation, DSBs were historically seen as rare, mostly therapy-induced DNA lesions. However, recent work unequivocally revealed that endogenous DSBs occur far more frequently that initially believed, including in physiological conditions, such as neuron stimulation, and mainly fall within transcribed loci, partly due to topoisomerase II activity. Notably, altered repair of these DSBs is not only emerging as a driver of oncogenesis but also of many developmental, neurological and aging-associated diseases. Our lab has pioneered the discovery of a dedicated pathway that, alike TC-NER for damaged nucleotides, is actually mobilized to repair such DSBs in transcribed loci, coined as Transcription Coupled DSB repair (TC-DSBR). This pathway entails chromatin signaling, nuclear reorganization and the regulation of transcription, but remains poorly characterized overall. Using advanced genomics, proteomics and microscopy, here we intend to perform an in-depth characterization of the TC-DSBR protein network, of the function of chromatin and nuclear organization in this process, to explore its potential as a target for cancer therapy and to investigate its relevance in maintaining genomic and epigenomic integrity in physiological conditions that trigger DSB in active genes, here in stimulated neurons. By deciphering the mechanisms that ensure repair of DSBs in transcribed loci, this project holds the potential to expand our knowledge on the biogenesis of translocations and cancer onset, to provide new topoisomerase-poison-based therapeutic strategies but also to provide major breakthroughs in our understanding of neurodegenerative diseases.

Mots-clés : dsb repair,chromatin,chromosome conformation,nuclear organization,neurons
Projet ERC : SexMeth (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : UK Research and Innovation — Pays : Royaume-Uni — Rôle : Partner
Acronyme de l'entité : UKRI
Type d'entité : Recherche
Financement ERC de l'entité : 1335269.25 €

DNA methylation is an epigenetic mechanism carrying regulatory information across generations in plants and animals. Germlines – called sexual lineages (SLs) in plants – are essential for understanding methylation-based epigenetics because they mediate inheritance and undergo large-scale methylation reprogramming. Germline methylation reprogramming is also crucial for reproduction. However, our understanding of plant SL epigenetics is in its infancy. I have done some of the first and most influential work in plant SL epigenetics, and developed advanced techniques for the isolation and epigenomic analysis of rare plant cell types. Recently my lab discovered that the small RNA-directed DNA methylation pathway, which generally only targets transposons, induces methylation of genes specifically in SLs, thereby regulating gene expression and meiosis. Our results also indicate that genic methylation is established in meiocytes (the origin of the male SL) by soma-derived small RNAs that are attenuated by heat stress, suggesting the hypothesis that environmentally malleable heritable information flows from soma to the germline. We will test our hypothesis and reveal the molecular mechanisms underlying SL-specific DNA methylation in plants by pursuing the following objectives: 1. Determine how SL-specific genic methylation is established in meiocytes 2. Reveal how sRNA biogenesis and transport mediate DNA methylation in the male SL 3. Elucidate environmental modulation and transgenerational inheritance of SL methylation Our research will reveal how new genomic loci become methylated and stay methylated through cell divisions, and how methylation is adjusted by the environment and carried to the next generation to influence phenotype. This knowledge will revolutionize our understanding of developmentally regulated methylation reprogramming, and will be invaluable for site- and/or cell type- specific engineering of DNA methylation.

Mots-clés : dna methylation,sexual reproduction,arabidopsis
Projet ERC : altEJrepair (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Institut Curie — Pays : France — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1188671.25 €

DNA repair pathways evolved as an intricate network that senses DNA damage and resolves it in order to minimise genetic lesions and thus preventing tumour formation. Gaining in recognition the last few years, the alternative end-joining (alt-EJ) DNA repair pathway was recently shown to be up-regulated and required for cancer cell viability in the absence of homologous recombination-mediated repair (HR). Despite this integral role, the alt-EJ repair pathway remains poorly characterised in humans. As such, its molecular composition, regulation and crosstalk with HR and other repair pathways remain elusive. Additionally, the contribution of the alt-EJ pathway to tumour progression as well as the identification of a mutational signature associated with the use of alt-EJ has not yet been investigated. Moreover, the clinical relevance of developing small-molecule inhibitors targeting players in the alt-EJ pathway, such as the polymerase Pol Theta (Polθ), is of importance as current anticancer drug treatments have shown limited effectiveness in achieving cancer remission in patients with HR-deficient (HRD) tumours. Here, we propose a novel, multidisciplinary approach that aims to characterise the players and mechanisms of action involved in the utilisation of alt-EJ in cancer. This understanding will better elucidate the changing interplay between different DNA repair pathways, thus shedding light on whether and how the use of alt-EJ contributes to the pathogenic history and survival of HRD tumours, eventually paving the way for the development of novel anticancer therapeutics. For all the abovementioned reasons, we are convinced this project will have important implications in: 1) elucidating critical interconnections between DNA repair pathways, 2) improving the basic understanding of the composition, regulation and function of the alt-EJ pathway, and 3) facilitating the development of new synthetic lethality-based chemotherapeutics for the treatment of HRD tumours.

Mots-clés : dna repair,alternative end joining,homologous recombination,synthetic lethality
Projet ERC : MetDNASecStr (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Imperial College London — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1638041.0 €

DNA replication is an essential process for genome duplication, cell division and ultimately organismal survival that ensures faithful transmission of the genome to progeny. Certain genomic loci represent major obstacles to DNA replication including fragile sites, G-rich tracts and repetitive sequences, such as ribosomal DNA and telomeres. Mammalian telomeres have the propensity to adopt complex DNA secondary structures, including telomere-loops and telomeric G-quadruplex DNA, which are believed to play essential roles in telomere maintenance. However, recent work has established that these structures are also a hindrance to DNA replication and failure to stabilise, repair or restart the replication fork is a potential source of genome instability, the hallmark of many diseases including cancer. Despite recent advances, the mechanisms that facilitate DNA replication at telomeres and other hard to replicate loci throughout the genome remain unclear. This proposal aims to address this important question in order to discover and decipher the mechanisms that help DNA replication through DNA secondary structures. I propose using multidisciplinary approaches to investigate the cellular response to replication stress at telomeres and the enzymatic activities that result in telomere replication aberrations, which will involve direct visualisation of telomere abnormalities using complementary DNA related methodologies and analysis of novel telomere-associated complexes. I also plan to determine the nature/structure of fragile telomeres, which remains poorly defined and represent a central question for the field using visualisation of biological molecules and proteomics. The detailed investigation of the function of known and new factors that facilitate telomere DNA replication represent an outstanding challenge that will provide a novel framework for understanding the contributions of replication factors in general DNA replication, genome stability and cancer in humans.

Mots-clés : telomeres,mammalian systems
Projet ERC : nanoDNArepair (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : Chalmers University of Technology — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

DNA-protein interactions are at the core of the function of every human cell. Single DNA molecule methods have revolutionized our understanding of such interactions. A vast majority of these methods are based on attaching the DNA, at one or both ends, to a bead or a surface. This gives ultimate control of the positioning of the DNA molecules and forces that can be applied to them but makes it difficult to investigate interactions with DNA ends, especially when more than one single DNA molecule is involved. Such interactions are however of fundamental importance, not the least in the repair of DNA double-strand breaks (DSBs), the most serious damage to our genetic material. In nanoDNArepair I will develop and use a method that allows analysis of DNA-protein interactions on large, single DNA molecules for DNA freely suspended in solution. The method is based on entropically trapping and stretching genomic length DNA molecules in nanofluidic channels and using an orthogonal nanoslit to expose the trapped DNA to proteins of interest. In contrast to all existing nanofluidic devices, the novel device allows active addition (or removal) of proteins to (from) the confined DNA and positioning of two or more DNA molecules in close proximity. We will use the device to study the main repair machinery for DSBs, non-homologous end-joining (NHEJ). In NHEJ a machinery of proteins finds the broken ends, protects them, holds them close and ligate the break. These steps are difficult to study with traditional single DNA molecule techniques, but perfectly suited for the nanofluidic device. The single molecule analysis can reveal stoichiometry, kinetics and dynamics of these processes, as well as identify important sub-populations, which is crucial for understanding the process. The outcome of the project will, in addition to the device, be improved understanding of genetic diseases, including cancer and strategies for development of novel drugs.

Mots-clés : nanofluidcs,non homologous end joining single dna molecules,dna repair