Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : PRION2020 (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : University of Zurich — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UZH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Transmissible spongiform encephalopathies (TSE) are caused by the ordered aggregation of PrPC into prions consisting of PrPSc. Similar pathogenetic principles operate in Alzheimer’s and Parkin-son’s disease, and a growing list of further diseases whose prevalence is steadily rising. Familial TSE are invariably associated with PrPC mutations, and the dearth of genetic modifiers has hampered our understanding of prion diseases. Therefore, the first objective of my proposal utilizes a cell-based high-throughput quantitative prion replication assay (developed during my previous ERC instalment) for genome-wide unbiased screens employing new genetics tools (CRISPR, siRNA li-braries, next-gen sequencing) to identify modifiers of prion uptake, replication, and secretion. The second objective aims at clarifying the basis of prion neurotoxicity and will be developed along two alleys: (a) we will uncover the molecular basis of spongiosis (the neuronal vacuolation characteristic of prion diseases), which we suspect to be a main driver of pathology, and (b) we will perform CRISPR-based synthetic lethality screens to identify genes that become essential to prion-infected cell lines (which do not experience prion toxicity) and may not be expressed by neurons. The third objective is to understand the function of PrPC in cellular physiology, and focuses on our evidence that (a) PrPC interacts with an orphan G-protein coupled receptor to maintain peripheral myelin integrity and (b) that PrPC may trigger cell death in response to ER stressors. While certain pathways of degeneration will undoubtedly be specific to prion infections, I expect that some targets will prove common to a variety of protein aggregation diseases including Alzheimer’s and Parkinson’s disease, and may perhaps translate into novel diagnostics and therapeutics. Hence the proposed project may not only open new perspectives in prion biology but also yield insights applicable to much more common diseases.
Projet ERC : DEMSEC (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Leiden University — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1075109.0 €

Transparency in politics is the mantra of democratic governance. Should state secrecy, such as classified intelligence programs or closed-door political bargaining be abolished? Despite its revered status, many feel that complete transparency would undermine effective functioning of governments. Take the public responses to the Wikileaks disclosures: many of the disclosures were assessed favorably, but few people defended the idea of total transparency that inspired them. If both complete secrecy and complete transparency are to be rejected, what ratio of secrecy and transparency in politics should we seek? Democratic theory leaves this question unanswered: no systematic assessment of the role of secrecy in a democracy is available. This project solves this problem. By employing the tools of analytic political philosophy, social choice and game theory, we develop a theory of democratic secrecy centred around three theses: 1. Secrecy in exercising executive and legislative power can be democratically authorized; 2. Secrecy protects the integrity of democratic decision-making processes; 3. Balancing secrecy and transparency is an exercise in balancing the values underlying democratic authority and democratic decision-making mechanisms. The results of this philosophical study set a new course in democratic theory by demonstrating that democratic governance requires less openness than traditionally assumed. To complement the theory, criteria for political accountability for wielding political secrets and criteria for assessing responsibility for their unauthorized disclosure are designed. Our results have practical relevance: understanding when and why secrecy is morally acceptable may change the policy approach to transparency provisions, and provide a better fit between the “public right to know” and the needs of governments. Scholars from Poland and the Netherlands assess the use of governmental secrecy in these two, respectively old and new, EU member states.

Mots-clés : political philosophy,secrecy,transparency,democracy,legitimacy,collective decision making,executive power,legislative power,unauthorized disclosures,leaks,the media
Projet ERC : TOLERANCE (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Eindhoven University of Technology — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : TU/e
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1020910.0 €

Transplantation is a life-saving procedure for patients who suffer from end-stage organ failure. While the discovery of potent immunosuppression offers a solution to the previously insurmountable problem of organ rejection, transplant recipients still face substantial problems, including chronic rejection and adverse effects related to the chronic use of immunosuppressive drugs. Therefore, transplantation field’s ‘holy therapeutic grail’ is immunological tolerance induction without the need for chronic immunosuppression. Our recent work has identified innate immune responses, and in particular trained immunity, to play a critical role in transplantation. Based on compelling preliminary data, I hypothesize that trained immunity-induced myelopoiesis and hyperinflammation are proximal causes of T and B cell immunity and therefore are compelling therapeutic targets to induce immunological tolerance and significantly improve allograft survival. We will tackle the central hypothesis from the vantage points of medicine & immunology and biomedical engineering by pursuing two objectives: Objective 1 Medicine & Immunology – To mechanistically decipher innate immune responses and myelopoiesis in kidney transplant patients. Objective 2 Biomedical Engineering – To develop immuno-imaging and nanomedicine approaches that target innate immunity in transplantation. We have developed a comprehensive preclinical development program to evaluate these novel methods in a kidney transplant mouse model. This Program’s successful completion will yield unique nanobiologic immunotherapies and immunoimaging strategies, which can be employed to take control of the innate immune response and promote allograft tolerance in transplantation, but can also be adopted to treat other conditions that are characterized by an exacerbated immune response, including infections, cancer and cardiovascular diseases.

Mots-clés : nanomedicine,nano immunotherapy,kidney transplantation,molecular imaging,precision medicine
Projet ERC : GLASST (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 51250.0 €

Transport is a major determinant of population health. Adverse health impacts are greatest in lower and middle income cities. Research and policy models are being used to predict how changes in travel patterns and related exposures (e.g. physical activity, air pollution, and road traffic danger) might influence health outcomes (e.g. injuries, heart disease, some cancers and diabetes). However, current methods are not able to produce reliable or comparable results for the questions researchers and policy makers are asking. Results are needed for settings with limited data. Methods are needed to integrate with the separate discipline of transport modelling. There is a need to develop the next generation of transport and health impact models and tools that are academically robust and practically useful. I will develop the next generation of models through the following objectives: 1. To develop methods and computer programs that allow researchers to compare health impact models and data. By collating and comparing models across many settings and scenario I will identify the circumstances in which variation in model structure and parameters makes an important difference to model results. This information will be used to create and test models for new settings and problems. 2. To integrate health impact modelling methods with the models used by transport researchers. This will make health impacts visible to transport planners. I will investigate the added value that land use/transport models can bring to health impact modelling from improved spatial and temporal detail and following households’ residential location over time. 3. To use the methods from (1) and findings from (1) and (2) to develop a global city-level model and tool that utilises the best data available in any setting to create comparable exposure and disease estimates. This will transform the opportunities for modelling health impacts of transport policies and scenarios across the world.

Mots-clés : walking,cycling,modeling,travel,health impacts,physical activity,air pollution,road traffic injuries,greenhouse gas emissions,noise,travel demand modeling,impact assessment
Projet ERC : NEUROPRECISE (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Ludwig-Maximilians-Universität München — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : LMU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499998.0 €

Traumatic brain injury (TBI) is very common and affects 1.8 million Europeans seeking medical help each year. TBI is a major challenge for healthcare providers and poses an enormous economic burden. For decades, TBI has been characterized by severity of symptoms for diagnosis, prognosis, and therapy. However, this classification system is limited since it does not allow to predict long-term outcome after TBI. This state of affairs thus hinders the advancement of TBI research and the development of therapies. The field is thus in dire need of a novel understanding and classification of the individual’s response to brain injury and, most importantly, a fresh perspective on potential targets for effective treatment and prevention of long-term impairment. My main hypothesis is that brain injury leads to a neurosteroid response with inter-individual variability and that this response is associated with the trajectory of recovery. I further hypothesize, that the most vulnerable patient cohorts, such as adolescent girls, show distinct patterns of neurosteroid response associated with an increased risk for persistent symptoms. NEUROPRECISE proposes a longitudinal cohort study 1) to characterize neurosteroid response with respect to age and sex in children and adolescents with TBI, 2) to evaluate the association of the neuroimaging derived individual injury profile with neurosteroid response, and 3) to explore individual differences in neurosteroid response as a potential target for acute therapy and prevention of chronic symptoms with respect to age and sex in a rodent model. NEUROPRECISE will overcome a critical barrier towards the treatment of TBI by establishing a novel, biological-driven way to stratify TBI patients based on inter-individual differences in the response to TBI. By exploring the individual neurosteroid response as potential therapeutic target, NEUROPRECISE will bring the power of precision medicine to neurotrauma research.

Mots-clés : mild traumatic brain injury,neurosteroid profile,personalized medicine,adolescents,females,prognosis,therapy,neuroimaging,mr spectroscopy,diffusion mri,animal experiment,hormones
Projet ERC : NeuroRemod (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Institut du cerveau — Pays : France — Rôle : Partner
Acronyme de l'entité : ICM
Type d'entité : Recherche
Financement ERC de l'entité : 240703.79 €

Traumatic events such as strokes or lesions to the adult brain can trigger large-scale reorganization of neuronal activity thought to be critical for functional recovery. The anatomical and molecular events underlying such reorganization remain an enigma. While rapid and short term changes of connections at the synaptic scale are widely studied, little is known about the principles and mechanisms of long-term and large-scale reorganization of axonal branches in mature circuits. I hypothesize that long-range axonal branching events in a minority of neurons contribute significantly to the plasticity and reorganization of adult neuronal circuits via unknown intrinsic mechanisms of axons survival and extrinsic environmental cues. A major reason why so little is known about axon dynamics in the adult brain has been the immense technical challenge of imaging rare axonal events in the dense meshwork of the adult brain. To solve this problem, I will apply new 3D imaging and genetic tools I developed to help visualize and quantify axons and synapses in the whole brain in an unbiased way. First, I will study the brain-wide neurite and synaptic dynamics after lesion and their effect on circuit function and homeostasis to shed light on the scale of brain plasticity. Second, I will characterize the intrinsic molecular pathways controlling activity-driven branch dynamics with viral approaches. I will make extensive use of tissue clearing, 3D imaging, and state-of-the-art image analysis pipelines to streamline the analysis of neuronal network properties. Third, I will investigate the extrinsic molecular and environmental factors promoting axonal dynamics in the context of adult brain structural plasticity. By generating a conceptual and mechanistic framework for the properties and mechanisms of injury induced brain reorganization, this study may contribute to the future design of new strategies to promote brain repair and curb the progress of neurodegenerative diseases.
Projet ERC : RHIZOCARBON (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Trees are unique in that responses at the organism level, being upscaled to forest canopies, bear large effects on the cycling and distribution of water and carbon in regional and global scales. Hence, tree carbon allocation dynamics are central not only to tree eco-physiology but also to global biogeochemistry. While tree aboveground carbon fluxes have been extensively studied, belowground fluxes, such as root respiration, growth and exudation have been mostly overlooked due to poor access to the root system. This project is set to address this knowledge disparity by answering key questions concerning belowground carbon flow. In one line of research, we will study the trees' “in-house” management of carbon flow, inspired by our recently achieved first comprehensive tree carbon balance calculation, which indicates that carbon reserves serve as a buffer that accommodates large fluctuations in carbon supply and demand. This will be complemented by an exploration of the inter-tree carbon supply network of mycorrhizal fungi routes, an investigation prompted by our discovery that mature trees in a mixed forest transfer unprecedented amounts of carbon among each other via fungal networks. Computational models will be applied to identify the evolutionary requirements for the development of belowground carbon transfer in a mycorrhizal network. We will dive into the highly complex soil system not in an artificial medium system – but in a mixed forest site, complemented by greenhouse experiments simulating forest tree communities. To trace below-ground carbon transport, we will apply our novel methodology of continuous, in vivo, combined measurement of 13CO2 carbon allocation and flux rate. This novel ‘rhizosphere expedition’ will decipher the key belowground carbon transport processes, shedding light on the extent to which trees and fungi regulate them and facilitating predictions of carbon storage in changing climate and forests.

Mots-clés : tree eco physiology,carbon allocation,forest rhizosphere,root exudation,mycorrhiza
Projet ERC : TRIPLECON (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : Leiden University — Pays : Pays-Bas — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 59925.0 €

Triple negative breast cancer (TNBC) is an aggressive disease, accounting for 15-20% of breast cancer cases, but disproportionally causing breast cancer-related death. TNBC does not express the targetable receptors ER, PR, and HER2 that are known to drive other forms of breast cancer. Mainstay practice for TNBC in the clinic is to treat with non-targeted cytotoxic chemotherapies. Long-term outcomes are however still poor, most likely owing to intrinsic drug resistance. Clinical trials have attempted to explore molecular targeted therapies to block dysregulated growth factor receptors in TNBC, for instance, epidermal growth factor receptor (EGFR), as it is overexpressed in ~80% of TNBC. Yet, giving the long-standing availability of clinically approved EGFR-targeted therapies, such as lapatinib, the clinical benefit of single agent therapy is unsatisfactory, owing to the compensatory dysregulated signaling pathways. In our ongoing ERC – Advanced Grant Triple-BC (#322737) we are striving to explore combinatorial molecular targeted therapies to concomitantly block the identified dysregulated signaling pathways. Our preliminary work revealed that an inhibitor targeting cyclin-dependent kinase 9 (CDK9) strikingly synergized with targeting EGFR receptor family signaling to inhibit cell proliferation of TNBC cell lines. The overall goal of this PoC project is to exploit this novel finding and provide proof-of-concept evidence that stalling CDK9 signaling may enable successful targeted combination therapy in TNBC. Therefore, the specific objective is to assess the pharmacological response of dual EGFR-CDK9 targeting in TNBC patient-derived xenograft (PDX) mouse models in vivo. We envisage that this PoC project will translate our identified successful synergistic treatment into an effective future novel and safe combinatorial targeting strategy benefiting TNBC patients.

Mots-clés : triple negative breast cancer  drug resistance  synthetic lethality  patient derived xenografts  pdx   dual egfr and cdk9 inhibition  combinational targeted therapy
Projet ERC : INCLUDE (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
Entité participante : University of Bern — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1596376.81 €

Tropical deforestation is an important contributor to climate change, through the release of significant amounts of carbon in the atmosphere. The main proximate cause of deforestation in tropical regions is agricultural expansion, followed by timber extraction. The general objective of this research is to understand how the interaction of technological, environmental, economic and social factors influence land use dynamics, including household decisions, about agricultural expansion and resource extraction in sensitive tropical regions. More specific questions relate to the role of various governance structures, particularly those recognizing common property regimes of land tenure to indigenous and rural communities, and the deliberative evaluation about the opportunity of reforming such structures in order to reduce deforestation and forest degradation. Although such aspects have been addressed in a variety of contexts, the approach proposed here is novel as a) it explicitly models the interaction between institutional, environmental, technological and socio-economic factors at different spatio-temporal scales, b) it specifically focuses on the governance structures associated with different land tenure regimes through the lenses of Social Network Analysis (SNA), c) uses a Q-methodology framework to develop a participatory approach to study stakeholders’ perspectives and attitudes on the necessary governance interventions to prevent deforestation and forest degradation and d) it assesses the relationships between agricultural expansion, deforestation, governance structures and stakeholders’ attitudes, with particular attention to the sensitivity of household land use decisions and resource extraction. In order to meet the research objectives, this project will focus on the province of Salta in the dry Chaco in North-Western Argentina, a region characterized by high rates of land cover change and the presence of indigenous/rural communities.
Projet ERC : MEL-Interactions (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Tumor development emerges from an accumulation of somatic alterations that together enable malignant growth. These alterations are immensely diverse and the fate of a cell acquiring an alteration may depend on other alterations already present. Despite our progress in mapping the cancer genetic landscape and an expanding catalogue of cancer genes, a need arises to establish how alterations in cancer genes interact to transform healthy cells into cancer cells. Many fundamental questions regarding genomic interactions remain open. For example, we do not know which proteins make up signaling pathway hubs and in which genetic contexts, how genetic alterations interact functionally, how cancer genetic alterations influence the interaction with T cells and how these affect patient response to therapy. The recent growth in the number of genomics data sets gives rise to a parallel increase in statistical power to detect more complex associations allowing robust analyses of complex interrelated genomic networks. In this proposal we suggest to employ our expertise and unique toolsets, to shed new light on the complex interrelated networks formed in melanoma. We propose to combine state-of-the art high content tools with mechanistic studies to discover the structure of signaling-hub organization in melanoma (Aim 1), functionally characterize the complex genetic interactions within the melanoma genome using genome engineering approaches (Aim 2), and to decipher the immuno-genetic interactions between melanoma and T cells (Aim 3). Importantly, we will try to bridge the knowledge gap in deciphering melanoma-specific gene interactions, protein interactions and interactions with T cells by creating new tools and experimental models. Our findings should make an important step towards an unprecedented, thorough and multifaceted understanding of melanoma biology. More broadly, we believe these approaches provide a paradigm for addressing similarly complex questions in other cancers.

Mots-clés : cancer genetics,somatic mutation,sequencing,targeted therapy,signal transduction