Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : Trep-AB (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Washington — Pays : Etats-Unis — Rôle : Partner
Acronyme de l'entité : UW
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 348111.19 €

Current therapeutic options for human treponematoses, syphilis and yaws, are, broadly speaking, restricted to one antibiotic: injectable penicillin. The drug susceptibility profile of Treponema pallidum (T.p) is unknown because the microorganism could not be grown in culture. Treatment failure after penicillin has been related to syphilis bacteria that survive in the central nervous system (CNS) and the potential of strains to acquire resistance to penicillin has recently been recognized. Yaws can be treated with azithromycin but there is a real risk that macrolide-resistant strains disseminate widely and jeopardize the global eradication campaign. I propose a research program to have other validated treatment options with good CNS penetration that are efficacious for all the stages of treponemal infection. Our preliminary results using computational prediction of drug activity based on similarity to drugs with known activity against T.p. and other spirochetes shows several candidate antibiotics. I will take advantage of recent developments in culture methods for determination of drug susceptibility to test 20 prioritized drugs. These results will be confirmed in experimentally infected rabbits treated with the investigational drugs and assessed for lesion development and T.p. burden. My second approach will exploit the established expertise of my team conducting randomized clinical trials to evaluate the efficacy of the 2 most promising candidates compared to standard treatment to cure patients with syphilis/yaws. Such studies will incorporate in-depth studies of recurrent events among study participants, to further clarify the biological basis and identify mutations that confer resistance to B-lactams. New antibacterial oral drugs for the treatment of treponematoses will be a tremendous resource in case of penicillin treatment-failure, resistance, shortage, allergy, or for use in yaws combination regimens to reduce the likelihood of resistance selection.

Mots-clés : syphilis animal model,difficult clinical management in syphilis,antimicrobial equivalence trial in syphilis,syphilis whole genome sequencing,mass azithromycin treatment of yaws
Projet ERC : E-motion (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Wageningen University & Research — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : WUR
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1950000.0 €

Current water treatment technologies are mainly aimed to improve the quality of water. High-value nutrients, like nitrate and phosphate ions, often remain present in waste streams. Electro-driven separation processes offer a sustainable way to recover these nutrients. Ion-selective polymer membranes are a strong candidate to achieve selectivity in such processes. The aim of E-motion is to chemically modify porous electrodes with membranes to introduce selectivity in electro-driven separation processes. New, ultrathin ion-selective films will be designed, synthesized and characterized. The films will be made by successively adsorbing polycations and polyanions onto the electrodes. Selectivity will be introduced by the incorporation of ion-selective receptors. The adsorbed multilayer films will be studied in detail regarding their stability, selectivity and transport properties under varying experimental conditions of salinity, pH and applied electrical field, both under adsorption and desorption conditions. The first main challenge is to optimize and to understand the film architecture in terms of 1) stability towards an electrical field, 2) ability to facilitate ion transport. Also the influence of ion charge and ion size on the transport dynamics will be addressed. The focus of E-motion is set on phosphate ions, which is rather complex due to their large size, pH-dependent speciation and the development of phosphate-selective materials. Theoretical modelling of the solubility equilibria and electrical double layers will be pursued to frame the details of the electrosorption of phosphate. E-motion represents a major step forward in the selective recovery of nutrients from water in a cost-effective, chemical-free way at high removal efficiency. The proposed surface modification strategies and the increased understanding of ion transport and ionic interactions in membrane media offer also applications in the areas of batteries, fuel cells and solar fuel devices.

Mots-clés : physical chemistry,process engineering,separation processes,water treatment,sustainability,polyelectrolytes,ion selectivity,ion recovery
Projet ERC : LIMBo (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems 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 : 1199697.0 €

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 : 3MC (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : Utrecht University — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999625.0 €

Currently fuels, plastics, and drugs are predominantly manufactured from oil. A transition towards renewable resources critically depends on new catalysts, for instance to convert small molecules (such as solar or biomass derived hydrogen, carbon monoxide, water and carbon dioxide) into more complex ones (such as oxygenates, containing oxygen atoms in their structure). Catalyst development now often depends on trial and error rather than rational design, as the heterogeneity of these composite systems hampers detailed understanding of the role of each of the components. I propose 3D model catalysts as a novel enabling tool to overcome this problem. Their well-defined nature allows unprecedented precision in the variation of structural parameters (morphology, spatial distribution) of the individual components, while at the same time they mimic real catalysts closely enough to allow testing under industrially relevant conditions. Using this approach I will address fundamental questions, such as: * What are the mechanisms (structural, electronic, chemical) by which non-metal promoters influence the functionality of copper-based catalysts? * Which nanoalloys can be formed, how does their composition influence the surface active sites and catalytic functionality under reaction conditions? * Which size and interface effects occur, and how can we use them to tune the actitivity and selectivity towards desired products? Our 3D model catalysts will be assembled from ordered mesoporous silica and carbon support materials and Cu-based promoted and bimetallic nanoparticles. The combination with high resolution characterization and testing under realistic conditions allows detailed insight into the role of the different components; critical for the rational design of novel catalysts for a future more sustainable production of chemicals and fuels from renewable resources.

Mots-clés : supported nanoparticles,3d nanostructures
Projet ERC : UnderSCORE (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Ghent University — Pays : Belgique — Rôle : PI
Acronyme de l'entité : UGent
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Currently, forest management models focus predominantly on tree dynamics following interventions, and tend to ignore the plant species found below the trees on the forest floor (the understorey). This is a crucial oversight, as the understorey is the major component of biodiversity, provides vital ecosystem services, and can influence the overall functioning of the forest. As such, there is a need for a user-friendly tool to help predict key understorey plant performance indicators (e.g. biodiversity, share of species of conservation concern) across environmental contexts (e.g. macroclimate space, land-use history) and overstorey tree management (e.g. timber species choice, forest management systems, rotation times). Based on the outcomes and insights from the ERC Consolidator Grant PASTFORWARD we propose to solve the lack of a user-friendly tool for understanding vital understorey dynamics by first creating a prototype web-based Decision Support System (UnderSCORE). Creating this tool will transfer the research output of the ERC PASTFORWARD project into a form that is of direct use for policy makers and forest managers. Such a tool is not currently available but clear legal and societal imperatives (e.g. Natura 2000, European Biodiversity Strategy) require its development, and provide the context for its adoption by potential users. The first stage of this proof-of-concept project is to explore and confirm the understorey output data end users require, the input data they could typically provide, and the type of management interventions that they would typically contemplate. In the second stage, we will use this end user information, in conjunction with the distinctive scientific output of PASTFORWARD, to develop a prototype of the DSS. After the development of a first prototype, the DSS will be evaluated by a panel of end-users and then further optimized in order to guarantee maximal use and impact of UnderSCORE.

Mots-clés : understorey vegetation,global change,decision support system,forest management,forest policy
Projet ERC : Target to B-cure (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Leiden University Medical Center — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : LUMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Currently, most human autoimmune diseases are chronic conditions without a prospect of cure. My aim in this proposal is to meet the next major challenge, achieving cure in autoimmune disease. Many autoimmune diseases are characterized by autoantibodies and are remarkably responsive to B-cell targeted therapies, demonstrating that the autoreactive B-cell is central to disease pathogenesis. Nonetheless, the selective and permanent elimination of the autoreactive B-cell, both memory and plasma cells alike, is not presently feasible due to a lack of specific markers and treatments. My aim is to develop a vaccine that will allow the specific and long-lasting depletion of autoreactive B-cells, thereby inducing cure. Using the unique mutated sequences of autoreactive B-cell receptors (BCR), cytotoxic T-cells that specifically eradicate autoreactive B-cells will be induced. This concept extends the remit of vaccines beyond infectious diseases and cancer, into the sphere of autoimmune disease. Using the well-defined autoimmune disease rheumatoid arthritis (RA) as prototype, I will study the RA-specific autoimmune response. Our recent findings show that RA is characterized by a restricted, oligoclonally-expanded autoreactive B-cell pool. Using recently developed technologies, my team will identify autoreactive B-cells and the BCR repertoire at several (pre)disease stages. We will then determine the potency of the many non-germline-encoded mutations in BCRs as “neoantigens” amenable to T-cell recognition and vaccination. Incorporating these neoantigens into multiple long peptides covering the autoreactive B-cell repertoire, we will design patient-tailored vaccines and perform a phase I trial to determine the feasibility of specifically depleting disease-causing B-cells. This research will create the possibility for patient-tailored vaccines that can permanently eradicate auto-reactive B-cells in B-cell driven auto-immune diseases; diseases that are still incurable to date.

Mots-clés : autoimmunity,rheumatoid arthritis,autoreactive b cell,cytotoxic t lymphocyte,vaccine,antigen recognition
Projet ERC : MaintainMeth (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Institute of Science and Technology Austria — Pays : Autriche — Rôle : PI
Acronyme de l'entité : ISTA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 335492.0 €

Cytosine methylation is a chemical modification that is precisely copied when DNA is replicated. Because methylation can regulate gene expression, accurate reproduction of DNA methylation patterns is essential for plant and animal development and for human health. The enzymes that maintain DNA methylation have to work within chromatin, and particularly to contend with nucleosomes – tight complexes of DNA and histone proteins. How methylation of nucleosomal DNA is maintained remains unknown, and even the simple matter of whether nucleosomes hinder or promote methylation is controversial. My laboratory’s recent work with DDM1 – an ancient protein conserved between plants and animals that can move nucleosomes – and linker histone H1, which binds to nucleosomes and the intervening ‘linker’ DNA, has allowed us to formulate a model wherein movement of nucleosomes by DDM1 dislodges H1 and allows methyltransferases to access the DNA. Furthermore, this work revealed the existence of unknown factors required to maintain DNA methylation. My laboratory also discovered that DNA methylation influences nucleosome placement, thereby demonstrating that the interaction between DNA methylation and nucleosomes is bidirectional. My goal is now to deeply understand the connected processes of maintenance methylation and nucleosome placement. This will be achieved through three interconnected research strands: 1) Elucidation of how DNA methylation is maintained within chromatin. 2) Identification of new DNA methylation maintenance factors. 3) Determination of how DNA methylation influences nucleosomes in vivo. Our ultimate output will be the creation of a mathematical model of DNA methylation maintenance that will incorporate the bidirectional interactions between methylation and nucleosomes. This breakthrough will revolutionize research in the field by permitting the development of precise, quantitative hypotheses about the maintenance and function of DNA methylation within chromatin.
Projet ERC : ToCCaTa (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Technical University of Munich — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : TUM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999850.0 €

Cytotoxic T cells have enormous potential for prophylactic and therapeutic interventions against problematic acute or chronic infections and against malignant tumors. A major obstacle to utilizing them effectively is our limited understanding of the molecular foundation that is necessary for CD8 T cells to fulfil their pleiotropic functions. Equally important is to find solutions supporting the robust and safe induction of large numbers of pathogen- or tumor-specific T cells and strategies for customized generation of T cells equipped with a functional capacity that are optimized to the often contrasting needs of particular diseases. For instance, anti-tumor immunity requires large numbers of highly activated effector T cells, while resting memory cells with high proliferative potential in combination with tissue-resident memory cells are thought to enhance protection against viral infections. Similarly, the challenge in treating chronic infections and tumors is to overcome the hypo-functional “exhausted” stage of T cells, but therapeutic induction of the same mechanisms to attenuate an aggressive T cell response could be vital for treating autoimmunity or immunopathology in fulminant liver or lung infections. Thus, to develop prophylactic or interventional strategies through which qualitative aspects of T cell function can be adjusted is a current key challenge in the immunotherapy and vaccine field. We seek to promote such activities by performing research that aims to significantly augment our comprehension of how molecular particularities translate into functional diversity. By taking advantage of 1) experimental systems that specifically mimic disease relevant T cell phenotypes, 2) approaches to assess molecular diversity at single cell level, 3) effective strategies to alter gene expression, and 4) systematic and hypothesis-driven molecular screening, we anticipate the discovery of new targets to optimize immunotherapies for tumors and chronic infections.
Projet ERC : DEEPVOLC (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : University of Bristol — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 58225.0 €

DEEPVOLC will radically advance the way future activity is forecast at volcanoes by applying advances in artificial intelligence to transformative new geodetic datasets. 200 million people live within 30 km of a volcano. Accurate forecasting of volcanic eruptions is problematic because 1) it relies on human interpretation at individual volcanoes, 2) a volcano can behave in unexpected ways not previously seen at that location, and 3) most volcanoes are not instrumented. DEEPVOLC will address this by i) applying artificial intelligence, ii) using data for all volcanoes worldwide, and iii) exploiting advances in satellite monitoring. A key indicator of potential volcanic activity is deformation of a volcano's surface due to magma migrating beneath. Surface movements as small as a few millimetres can now be measured from space, using satellite-borne radar. A recently-launched European satellite mission, Sentinel-1, has transformed our ability to measure surface deformation at all of the world's volcanoes, acquiring data at least twice every twelve days. However, forecasting how deforming volcanoes will behave in the future remains challenging. In this project I will apply recently developed deep learning approaches to the satellite data. This is an entirely new approach to forecasting volcanic activity, which currently relies on the individual expertise available at each observatory, and which is only now made possible due to the launch of Sentinel-1 and advances in deep learning algorithms. DEEPVOLC will combine knowledge from all volcanoes that have been active in the era of satellite deformation observations, and will continue to improve as it ingests data from new activity. The main deliverable will be a system for volcano observatories that uses knowledge of how volcanoes behave globally to automatically identify deformation at volcanoes locally, and forecast how the deformation will evolve, indicating the probability of eruption.

Mots-clés : insar,sentinel 1,volcano deformation,deep learning,neural networks
Projet ERC : InflaCare (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Foundation for Research and Technology Hellas — Pays : Grèce — Rôle : PI
Acronyme de l'entité : FORTH;ΙΤΕ
Type d'entité : Recherche
Financement ERC de l'entité : 150000.0 €

DNA damage triggers the activation of innate immune signaling leading to chronic inflammation and the premature onset of e.g. rheumatoid arthritis, diabetes, metabolic diseases and neurodegenerative disorders in man. Based on our ERC consolidator program DeFiNER, we recently discovered that persistent DNA damage triggers the innate immune system stimulating broad inflammatory and antiviral immune countermeasures that lead to chronic inflammation and the premature onset of severe metabolic complications and neurodegeneration in mice. Here, we propose a sophisticated a therapeutic anti-inflammatory strategy aimed at lowering chronic inflammation in preclinical animal models with pronounced metabolic diseases or neurodegeneration. Unlike available anti-inflammatory therapies, the proposed therapeutic approach is non-immunogenic, allows the therapeutic cargo to circulate for extended periods within the body and to cross the blood brain barrier with no biocompatibility complications and minimal to no inherent toxicity issues in mice. This novel strategy provides, therefore, the means towards an innovative medicine that will effectively address real but unmet therapeutic needs for a wide range of devastating diseases associated with chronic inflammation.

Mots-clés : dna damage,chronic inflammation,age related diseases,exosomes,preclinical animal models