Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : Born-Immune (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Karolinska Institutet — Pays : Suède — Rôle : PI
Acronyme de l'entité : KI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1422338.77 €

Immune systems are highly variable, but the sources of this variation are poorly understood. Genetic variation only explains a minor fraction of this, and we are unable to accurately predict the risk of immune mediated disease or severe infection in any given individual. I recently found that immune cells and proteins in healthy twins vary because of non-heritable influences (infections, vaccines, microbiota etc.), with only minor influences from heritable factors (Brodin, et al, Cell 2015). When and how such environmental influences shape our immune system is now important to understand. Birth represents the most transformational change in environment during the life of any individual. I propose, that environmental influences at birth, and during the first months of life could be particularly influential by imprinting on the regulatory mechanisms forming in the developing immune system. Adaptive changes in immune cell frequencies and functional states induced by early-life exposures could determine both the immune competence of the newborn, but potentially also its long-term trajectory towards immunological health or disease. Here, I propose a study of 1000 newborn children, followed longitudinally during their first 1000 days of life. By monitoring immune profiles and recording many environmental influences, we hope to understand how early life exposures can influence human immune system development. We have established a new assay based on Mass Cytometry and necessary data analysis tools (Brodin, et al, PNAS 2014), to simultaneously monitor the frequencies, phenotypes and functional states of more than 200 blood immune cell populations from only 100 microliters of blood. By monitoring environmental influences at regular follow-up visits, by questionnaires, serum measurements of infection, and gut microbiome sequencing, we aim to provide the most comprehensive analysis to date of immune system development in newborn children.
Projet ERC : MITOMAD (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Ministry of Health — Pays : Espagne — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1995000.0 €

Immunometabolism is an emerging research field that promises to generate novel targets for manipulation of functional responses in immune cells. Pioneering studies are beginning to unveil how innate sensing leads to metabolic reprogramming of immune cells. We became interested in the possible metabolic consequences of innate sensing by myeloid cells because of our previous work showing how mouse and human dendritic cell (DC) subsets detect danger signals from microbes and damaged tissues. Our current data show that sensing of live bacteria triggers a profound reorganisation of the mitochondrial electron transport chain (ETC) in macrophages, with a switch in the relative contribution of ETC complexes I and II to mitochondrial respiration that impacts immune response. As we pursue novel strategies to manipulate DC function, and supported by our preliminary data in DCs, we hypothesise that innate sensing induces mitochondrial adaptations in DCs and that targeting mitochondrial metabolism will affect DC function. Our goals are: 1) to characterise how innate sensing of danger signals from microbes or from tissue damage modulate mitochondrial adaptations and metabolic reprogramming in mouse and human DC subsets; 2) to dissect the molecular mechanisms that connect innate sensing and mitochondrial adaptations in DCs, using biased and unbiased cutting-edge proteomics approaches; 3) to address the impact of manipulating mitochondrial biology on mouse and human DC metabolism and function; and 4) to assess the functional in vivo effects of targeting mitochondrial biology in DCs in homeostasis and disease. The characterisation of the molecular mechanisms that link innate sensing and mitochondrial metabolism with DC function will open new avenues for basic research in mitochondrial biology and for the emerging field of immunometabolism. Functional targeting of DC mitochondrial metabolism has great potential for the discovery of new strategies to modulate immunity and tolerance.

Mots-clés : dendritic cell,mitochondria,vaccination,immunotherapy,innate receptors,targeting dc subsets,immunity,tolerance,t cell memory,viral infection,cancer,asthma
Projet ERC : ImmunoBioSynth (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
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 : 2000000.0 €

Immunotherapy holds the potential to dramatically improve the curative prognosis of cancer patients. However, despite significant progress, a huge gap remains to be bridged to gain board success in the clinic. A first limiting factor in cancer immunotherapy is the low response rate in large fraction of the patients and an unmet need exists for more efficient - potentially synergistic - immunotherapies that improve upon or complement existing strategies. The second limiting factor is immune-related toxicity that can cause live-threatening situations as well as seriously impair the quality of life of patients. Therefore, there is an urgent need for safer immunotherapies that allow for a more target-specific engineering of the immune system. Strategies to engineer the immune system via a materials chemistry approach, i.e. immuno-engineering, have gathered major attention over the past decade and could complement or replace biologicals, and holds promise to contribute to resolving the current issues faced by the immunotherapy field. I hypothesize that synthetic biomaterials can play an important role in anti-cancer immunotherapy with regard to synergistic, safe, but potent, instruction of innate and adaptive anti-cancer immunity and to revert the tumor microenvironment from an immune-suppressive into an immune-susceptible state. Hereto, the overall scientific objective of this proposal is to fully embrace the potential of immuno-engineering and develop several highly synergistic biomaterials strategies to engineer the immune system to fight cancer. I will develop a series of biomaterials and address a number of fundamental questions with regard to optimal biomaterial design for immuno-engineering. Based on these findings, I will elucidate those therapeutic strategies that lead to synergistic engineering of innate and adaptive immunity in combination with remodeling the tumor microenvironment from an immune-suppressive into an immune-susceptible state.

Mots-clés : immuno engineering
Projet ERC : EPIC (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Innsbruck Medical University — Pays : Autriche — Rôle : PI
Acronyme de l'entité : MUI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2460500.0 €

Immunotherapy with checkpoints blockers is transforming the treatment of advanced cancers. Colorectal cancer (CRC), a cancer with 1.4 million new cases diagnosed annually worldwide, is refractory to immunotherapy (with the exception of a minority of tumors with microsatellite instability). This is somehow paradoxical as CRC is a cancer for which we have shown that it is under immunological control and that tumor infiltrating lymphocytes represent a strong independent predictor of survival. Thus, there is an urgent need to broaden the clinical benefits of immune checkpoint blockers to CRC by combining agents with synergistic mechanisms of action. An attractive approach to sensitize tumors to immunotherapy is to harness immunogenic effects induced by approved conventional or targeted agents. Here I propose a new paradigm to identify molecular determinants of resistance to immunotherapy and develop personalized in silico and in vitro models for predicting response to combination therapy in CRC. The EPIC concept is based on three pillars: 1) emphasis on antitumor T cell activity; 2) systematic interrogation of tumor-immune cell interactions using data-driven modeling and knowledge-based mechanistic modeling, and 3) generation of key quantitative data to train and validate algorithms using perturbation experiments with patient-derived tumor organoids and cutting-edge technologies for multidimensional profiling. We will investigate three immunomodulatory processes: 1) immunostimulatory effects of chemotherapeutics, 2) rewiring of signaling networks induced by targeted drugs and their interference with immunity, and 3) metabolic reprogramming of T cells to enhance antitumor immunity. The anticipated outcome of EPIC is a precision immuno-oncology platform that integrates tumor organoids with high-throughput and high-content data for testing drug combinations, and machine learning for making therapeutic recommendations for individual patients.

Mots-clés : cancer immunology,combination therapy
Projet ERC : NEURODIAM (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Chambre de commerce et d'industrie de région Paris - Île-de-France — Pays : France — Rôle : Partner
Acronyme de l'entité : CCI PARIS ILE-DE-FRANCE
Type d'entité : Organismes publics (hors enseignement & recherche)
Financement ERC de l'entité : 0.0 €

Implantable neuroprosthetic devices offer the promise of restoring neurological functions to disabled individuals. Tests demonstrated that an array of microelectrodes implanted in cortex allows to record activity of the brain and to induce a movement on prosthetic limbs or electrical stimulations restore some visual sensations. For these applications the life time and stability of the electrodes are critical features for the reliable operation of any implantable neuronal device. It’s also necessary to have high density implant with small electrodes to cover a large surface of the cortex to have access of neuronal code. A reliable packaging for long term implantable devices are in titanium or glass but not suitable in the case of ECoG (ElectroCorticoGraphy) implant. Indeed, it is necessary to achieve a polymer implant as a core material, to follow the topology of the brain surface. But in long term the polymer swells and moisture penetrates the implant and degrades its performances therefore reducing the lifetime. The goal of NEURODIAM project is to address two major challenges: - increase the lifetime of implant by a specific packaging, - reduce the size of the electrodes to be equivalent to the neurones size (10 µm) without degradation of noise and consequently increase the electrode density for a fine mapping of the cortex. To avoid performance drift of the implant, a new packaging solution completely hermetic will be developed based on the last developments of micro and nano structuration of diamond layer that combines conductive and intrinsic synthetic diamond. Fast ageing tests will be settled to demonstrate the viability of this diamond technology. In-vitro and in-vivo assessment will be performed to demonstrate the efficiency of these implants for recording and stimulation of neuronal tissue. This project will produce high performance diamond based technology that can be later used for various implants dedicated to fundamental studies in neurosciences.

Mots-clés : micro and nanotechnology,neuroprothesis,electrocorticography  ecog,diamond material
Projet ERC : STROMA (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Charité - Universitätsmedizin Berlin — Pays : Allemagne — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 161500.0 €

In 1984, Nossal wrote ‘‘A readership consisting of primarily anatomists has every right to question the favorite sport of research workers in cell immunology. This is to take a lymphoid tissue and totally destroy its beautiful and elaborately designed architecture to obtain simple cell suspension of lymphocytes, which are then asked to do more or less all the jobs of the original anatomic masterpiece’’. Growing evidence that lymph node (LN) stromal cells control the motility, activation and survival of lymphocytes has reinforced this view. These architectural cells assemble in 3D networks that regulate LN homeostasis and control its ability to remodel during inflammation. Understanding stromal cell biology is thus mandatory to our full comprehension of the immune system but this ambitious objective is technically challenging. As the complexity of the LN cannot be modelled in culture, knowledge gained from in vitro experiments is limited and will not address many relevant questions related to the biology of LN stromal cells, in particular (i) the elucidation of their origin and the precursor/product relationships that link them, (ii) the determination of their behavior in inflamed LNs and (iii) their subsequent fate in LNs that have returned to homeostasis. To this aim, I have developed several original, cutting-edge multicolor fluorescent reporter mouse models and computational modeling approaches to map the fate of single stromal cells and their progeny in situ. Using this innovative approach, my group will investigate the spatio-temporal behavior and molecular cues that orchestrate the development and dynamics of the major LN stromal cell populations in vivo, at steady state and under inflammatory conditions, at the single cell level. Because the proposed studies will unravel the precursor/product relationships linking the various stromal cell types, we anticipate to provide the first “Phylogenetic tree” of LN stromal cell development and remodeling.
Projet ERC : PERSISTDEBT (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : Pompeu Fabra University — Pays : Espagne — Rôle : PI
Acronyme de l'entité : UPF
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1208676.0 €

In 2007 the US and Europe were overwhelmed by a banking crisis, which was followed by a severe economic recession. Historical studies show that financial crises are followed by periods of substantially stronger contraction of aggregate output and employment than non-financial recessions. Those studies also point out that the best predictor of financial crises is an ex-ante strong credit boom which, after the beginning of the crisis, followed by negative overall credit growth. Lastly, financial crises take a long time until recovering the pre-crisis levels. Why are the effects of credit shocks so strong and persistent over time? Is this effect explained by costly household deleveraging? What is the effect of household debt on consumption, savings and employment? Are there any benefits of debt in crises? Do some effects of the financial crisis work through a reduction in credit supply to firms and projects with high innovative content and productivity (high overall return, but with high credit and liquidity risk for the lenders)? Or are the cleansing effects in financial crises concentrated on the less productive firms? Can macroprudential policies based on strict control of loan-to-value ratios stop the building up of excessive household debt? We plan to construct several new datasets to study these issues by merging information from different sources. For some issues, like the analysis of the effect of household debt on consumption and employment, we can take advantage of a natural experiment of randomized allocation of debt among individuals derived from the use of lotteries to allocate the rights to buy housing in Spain. In comparison to the existing literature, we can exploit the exogenous variation generated by these lotteries and some other combination of data (including exhaustive credit data) to obtain causal evidence and quantification on the interaction between debt, systemic risk, crises, and the new macroprudential policy.

Mots-clés : financial crises,systemic risk,credit,debt,balance sheet channel,macroprudential policy,innovation,debt overhang,loan evergreening,excessive risk taking,conflicts of interest,banking
Projet ERC : ERA (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : Stockholm University — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2222267.75 €

In 2015, the UN Sustainable Development Goals (SDGs) and the Paris Agreement on climate recognised the deteriorating resilience of the Earth system in the Anthropocene. Maintaining Earth in the interglacial state that enabled the world’s societies to evolve over the past 12,000 years will require industrialised societies to embark on global-scale social transformations. Otherwise, there is a real risk of crossing tipping points in the Earth system triggering abrupt and irreversible changes. A critical gap is that although nonlinear social and biophysical dynamics are recognized, we remain trapped in linear thinking. Global modelling and analyses – despite much progress – do not adequately represent nonlinear processes and abrupt changes, and social responses to sustainable development are incremental. The goal of this project is to fill this gap, by exploring the biophysical and social determinants of the Earth’s long-term stability, building up a novel community modelling platform for analysis of nonlinearity and abrupt shifts, and informing global sustainability policy processes. The project will investigate two hypotheses: 1) Interactions, feedbacks and tipping points in the biosphere could, even in the absence of continued high emissions from fossil-fuel burning, tip Earth into a new state, committing to global warming over 2C and possibly beyond 4C; and 2) Only nonlinear societal transformations that aggregate to the global scale can assure long-term stability of the Earth and keep it in a manageable interglacial state. The five research tasks are Task 1: analysis of nonlinear biosphere dynamics governing Earth resilience. Task 2: integrating nonlinear dynamics in World-Earth models. Task 3: exploring tipping points in social systems for large-scale transformation. Task 4: backcasting pathways for achieving the SDGs. Task 5: integrating World-Earth dynamics into online learning and virtual-reality games, e.g. Planet3 and Minecraft.

Mots-clés : earth system modelling,global sustainability science,resilience,scenarios,transformations
Projet ERC : EpiScope (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
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 : 1708775.0 €

In Eukaryotes, cellular identity and tissue-specific functions are linked to the epigenetic landscape and the multi-scale architecture of the genome. The packing of DNA into nucleosomes at the ~100 bp scale and the organization of whole chromosomes into functional territories within the nucleus are well documented. At an intermediate scale, chromosomes are organised in megabase to sub-megabase structures called Topologically Associating Domains (TADs). Critically, TADs are highly correlated to patterns of epigenetic marks determining the transcriptional state of the genes they encompass. Until now, the lack of efficient technologies to map chromosome architecture and epigenetic marks at the single-cell level have limited our understanding of the molecular actors and mechanisms implicated in the establishment and maintenance of the multi-scale architecture of chromosomes and epigenetic states, and the interplay between this architecture and other nuclear functions such as transcription. The overall aim of EpiScope is to unveil the functional, multi-scale, 3D architecture of chromatin at the single-cell level while preserving cellular context, with a toolbox of groundbreaking high-performance microscopies (Hi-M). Hi-M will use unique combinations of multi-focus and single-molecule localization microscopies with novel DNA labeling methods and microfluidics. Hi-M will enable the study of structure-function relationships within TADs of different chromatin types and correlate single-cell variations in epigenomic patterns to 3D conformations with genomic specificity and at the nanoscale. Finally, Hi-M will be used to develop a novel high-throughput, high-content method to unveil the full pairwise distance distribution between thousands of genomic loci at the single cell level and at multiple length-scales. Our findings and technologies will shed new light into the mechanisms responsible for cellular memory, identity and differentiation.

Mots-clés : nuclear architecture,epigenomics,super resolution microscopy,fluorescence in situ hybridization,single cell,topologically associating domains,development,high throughput microscopy
Projet ERC : DISLIFE (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Umeå University — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999870.0 €

In Europe today disabled people comprise some 65 million (10%). Yet they are marginalized in society and research, and little is known on how disabilities become liveable. This project challenges this bias by proposing to investigate ‘liveable disabilities’ as a function of disability and opportunity structures across time. It analyses four life course dimensions: disabled people’s (1) health and well-being; (2) involvement in education and work; (3) in a partner relationship and family; and (4) in leisure structures. Through this I identify liveable disabilities before, during and after the Swedish welfare state. The results are of significant cross-national interest as they form a useful baseline for what constitutes liveable disabilities, which helps governing bodies maximize opportunity structures for disabled people to participate fully in society. This proposal is unique in employing mixed-methods life course research across time. First, it involves quantitative analysis of Sweden’s long-term digitized population databases, which reflect how disability impacts on people’s educational, occupational, marital and survival chances. The statistical outcome is novel in demonstrating how different impairments intersect with human characteristics relative to society’s structures of the past 200 years. Second, qualitative analyses uncover how disabled people today experience and talk about the above dimensions (1-4) themselves, and how mass media depict them. Third, I make innovative studies of leisure structures, which may promote liveable disabilities. The proposal aims to establish me at the forefront of disability research. It benefits from my scholarship in history and demography and from three excellent centres at Umeå University I am connected to, funded by the Swedish Research Council. One centre researches populations, another gender. The third provides expertise in disability studies and ready access to stakeholders outside academia.

Mots-clés : disability,cross disciplinary,life course,intersectionality,gender,multi methods,inequality,statistics,populations,structures,databases,welfare,provisions