Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : ADDABU (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 143750.0 €

Hail and storm damages represent the most often occurring cases for building insurance companies. Currently, the damage is estimated by an insurance expert, visiting the damaged building and drafting a report. Researchers at the Computer Vision Lab at ETH Zurich joined forces with business and sales people, spinning out the company Casalva, to strongly reduce such costs via automated image analysis. The idea is that the insurers’ clients upload photos of the damages, which will then be analyzed automatically by a computer. This involves computer vision technologies – grounded in the ERC project VarCity – to recognize the damaged building structures and to analyze the corresponding textures as to assess the extent of the damage and the estimated costs for its repair. Cutting costs is not the only consideration, as the fast assessment of damages improves customer satisfaction and prevents the occurrence of additional damages because of a delayed repair (like water leaking before repair). Such follow-on damages are estimated to be 20% of overall costs on average and are therefore far from negligible. Guaranteeing a short term response currently is a major issue, as a single storm may affect thousands of buildings. Processing times tend to stretch out due to the peak in cases following such extreme weather events. Over half of hail storm damage cases concern facade structures. The VarCity project produced methods to automatically parse facades into such structures, and to select the best way to describe their textures. These will be refined to optimally deal with the application area. The remaining technical developments and risk mitigations will be funded through other means (a Swiss project that has already been submitted), while this Proof-of-Concept project will focus on equally important aspects like market analysis, development of a corporate identity and graphical house style for the Casalva spin-off, that has been created but should now get market introduction.

Mots-clés : image analysis,damage,building,insurance
Projet ERC : Cor-Edit-P (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
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 : 2499375.0 €

Heart failure represents a common cause of death in European societies and is frequently based on dilated cardiomyopathy (DCM) which might be caused by mutations in cardiomyocyte genes. While no specific treatment exists, new therapeutic options are a major unmet clinical need. As attractive novel key approach, Cor-Edit-P will use Crispr-Cas9 based gene editing for distinct gene therapy of genetic cardiomyopathy, using pigs as a unique, clinic-related large animal model system. My lab tailored highly cardiotropic adeno-associated viral (AAV) vectors and their use in pigs in vivo, applying precise, reliable and versatile Cas9 technology. Pioneering this approach, we were able to restore significant dystrophin expression in muscles and hearts of pigs suffering from Duchenne muscle dystrophy. Exploiting unique and cutting-edge technology, Cor-edit-P aims at specifically eliminating the underlying cause of genetic DCM to improve cardiac function, reduce the risk of deadly arrhythmias and increase span and quality of life. Cor-edit-P will - generate currently lacking porcine models of genetic cardiomyopathy, using AAV-Cas9 to induce mutations in sarcomere genes, e.g. titin (TTN) and ß-myosin heavy chain (MYH7); - exercise curative Crispr-Cas9 mediated gene editing of DCM in pigs in vivo, using the PLN-R14del mutation in the phospholamban (PLN) gene as prominent example; - use human patient-derived PLN-R14del ventricular progenitor cells for gene correction ex vivo followed by transplantation of corrected cells into PLN-R14del pigs. Our approach implements a new paradigm for treating genetic cardiomyopathy and develops Crispr-Cas9 based gene therapy in pigs to foster clinical translation. Our work will influence the development of gene therapy by industry and academia and will benefit patients suffering genetic cardiomyopathy, but also further genetic diseases which are manifold prevalent in Europe.

Mots-clés : gene editing,genetic heart disease,dilated cardiomyopathy,adeno associated virus,cas9
Projet ERC : IC-CCD-qHSC (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
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 : 2312500.0 €

Hematopoietic stem cells (HSCs) contribute to blood cell production throughout life and are found at rare, yet tightly regulated frequencies in adult bone marrow (BM). During embryonic and postnatal development, HSCs expand through continuous self-renewing proliferation. Upon entry into adulthood the vast majority of HSCs synchronously convert to a quiescent state. From then on, at any given moment very few HSCs are found in active stages of cell cycle, which suffices to compensate basal HSC loss due to differentiation or cell death. Since proliferation rates of individual HSCs are heterogeneous, entry and exit from cell cycle need to be coordinated at the level of the HSC pool. To date, the mechanisms that orchestrate this collective proliferative behavior and effectively control the maintenance of homeostatic HSC numbers remain unknown. In preliminary work for this project we have customized a pipeline that combines 3D microscopy, deep learning-based image analysis and spatial statistics. Using these tools, we observed that despite showing broad spatial heterogeneity, HSCs tend to cluster and accumulate in relatively large regions of the BM. We now postulate that molecular crosstalk between proximal HSCs enables them to perceive their local densities and triggers collective regulation of HSC function to preserve homeostasis. Through a multidisciplinary approach involving high-level microscopy, spatial analyses, comprehensive metabolomic profiling and single-cell transcriptomics we aim to 1) characterize the basic anatomical and functional features of spatial dependencies between HSCs 2) study the potential role of quorum-sensing mechanisms in HSC crosstalk and 3) investigate if competition for molecular resources in local neighborhoods contributes to maintenance of HSC homeostasis. Our research has the potential to unravel novel complex forms of cellular interplay and substantially advance our understanding of hematopoietic tissue organization.

Mots-clés : 3d imaging,deep learning,spatial statistics,hematopoietic stem cells,quorum sensing,cellular competition
Projet ERC : HEPCAN (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : PI
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 150000.0 €

Hepatocellular carcinoma is the most frequent primary liver cancer and owing to its very aggressive nature is amongst the leading cause of cancer mortality worldwide (IARC). The number of liver cancer-related deaths in Europe in 2018 amounted to 77 375, and this number is expected to keep rising, reaching an estimated number of more than 100 000 deaths in 2040 (IARC). Major causes include the hepatitis B and C viruses, alcoholism, Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis. All of these medical conditions trigger liver fibrosis by damaging the liver and are closely associated with the development of HCC. As a matter of fact, more than 80% of HCC develop in fibrotic or cirrhotic livers. Early stages of liver cancer do not usually produce symptoms, and many challenges are associated with the screening of HCC, leading to its late diagnosis. The absence of effective drug treatment for HCC makes its resection the first curative option with most of the patients experiencing HCC recurrence within 5 years. All these factors contribute to the poor prognosis of the HCC patients. Sorafenib is the only currently approved systemic therapy for advanced HCC in the EU, only prolonging survival by an average of 3 months, the treatment often leads to drug resistance. Indeed, intra-tumor heterogeneity strongly constrains the therapeutic benefit of precision medicine and triggers drug-resistant sub-population of cells. Consequently, persistent treatment of drug-resistant tumor cells may accelerate tumor progression, suggesting that inappropriate and continual use of a compound on drug-resistant cancer cells is not recommended. Thus, there is an urgent unmet medical need to identify and to validate the therapeutic efficacy of new valuable molecules – i.e. targeting the existing drug-resistant cell populations -that could be used in monotherapy or in combination therapy with FDA-approved drugs to improve HCC treatment responses.

Mots-clés : liver disease,cancer,hepatocellular carcinoma,drug development,liver cancer model,antibody,cancer treatment
Projet ERC : ExploDProteins (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Basel — Pays : Suisse — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1940756.0 €

Here I propose to use small molecules to degrade proteins specifically around sites of DNA damage by using the damage itself as a homing signal. The approach will create new ways to study DNA damage, but will also offer translational possibilities in cancer. Cancer cells are often acutely sensitive to DNA damage because they have one or more faulty DNA damage response (DDR) pathways – a feature that makes them highly dependent on their remaining DNA repair systems. We will pioneer two novel and related chemical approaches for selectively killing cancer cells by modulating DDR pathways with bifunctional DNA damaging molecules. We will do this by reprogramming E3 ligases. E3 ligases are modular multi-protein complexes that destabilize cellular proteins by catalysing the formation of polyubiquitin chains on its substrates, which serve as a signal for proteasomal degradation. A recent revolutionary advance in chemical biology is to use small molecules to reprogram the protein degradation specificity of E3 ligases. By degrading proteins instead of inhibiting them, these small molecules achieve levels of functional modulation typically only possible with genetic techniques. We are inspired by this new protein degradation technology, but will take it in a new direction. Chemical damage of DNA recruits E3 ligases as well as critical DDR proteins in preparation for DNA repair. We will invent a new generation of small molecule protein degradation catalysts by repurposing these natural responses to DNA damage. We will accomplish our goal with three aims: Aim 1: Use DNA damage as a homing signal for induced protein degradation Aim 2: Use direct repair of DNA damage by the repair protein MGMT to promote the degradation of other proteins Aim 3: Promote pleiotropic protein degradation by recruiting broadly acting E3 ligases to sites of DNA damage I propose an ambitious project that will create conceptually novel ways to study the DDR and potentially build new medicines.

Mots-clés : induced protein degradation,dna damage,ubiquitin proteasome pathway,small molecules to reprogram biology
Projet ERC : hmqChIP (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Karolinska Institutet — Pays : Suède — Rôle : Partner
Acronyme de l'entité : KI
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 43000.0 €

Here, we develop a highly multiplexed, quantitative, ChIP-Seq technology (hmqChIP-Seq) for commercial exploitation in high-throughput profiling of epigenetic drug on- and off-target effects. Screening efficacy and toxicology of drug candidates in early stages of development has been recognized to be an essential part of drug screening. 90% of all Phase I drug candidates do not reach FDA approval and it is estimated that a quarter of failures relates to unexpected toxicity in humans. This is stunning given that all Phase I drugs have undergone animal-heavy battery of toxicologic tests and showcases the importance of expanding the screening capabilities for drug efficacy and toxicology in human cell-based assays, be it standard culture, organoids or engineered tissues. We believe that the interaction of drugs with the epigenome is an understudied/undervalued area of pre-clinical testing and epigenetic drug profiling will be key in predicting long term outcome in humans. With hmqChIP-Seq, 96 or more drug conditions can be screened against 24 or more epigenomic markers, such as histone or DNA post-translational modifications using specific antibodies and next-generation sequencing read-out. The method development aims to reduce the necessary input material to 1000 cells per condition, allowing it to be placed downstream of typical high-throughput cell-based drug screening assay in a variety of relevant human cell models, such as induced pluripotent stem cells, engineered tissues, organoids. The technology provides a framework for high-throughput, low cost, elucidation of short and long term action and toxicology of epigenetic drugs, or any drug candidate that could affect epigenetic markers.

Mots-clés : epigenomics,high throughput screening  hts,drug screening,drug toxicity,cell based screening
Projet ERC : Treat-HSP (Horizon 2020, appel 2018, Proof of concept grants)
Entité participante : Institut du cerveau — Pays : France — Rôle : PI
Acronyme de l'entité : ICM
Type d'entité : Recherche
Financement ERC de l'entité : 150000.0 €

Hereditary spastic paraplegias are a group of rare neurodegenerative diseases due to the degeneration of the long axons of cortical motor neurons. Some complex forms of the disease are also characterized by cognitive impairment. Currently, the only available treatments are symptomatic, act on the motor symptoms and do not prevent or delay the disease progression. There is therefore a strong demand of clinicians as well as of patients and their families for the development of any treatment that could delay the onset and/or the progression of the disease. We have developed a genetic mouse model of a complex form of hereditary spastic paraplegia, the SPG11 form that is extremely invalidating as the patients need to be taken in charge by families or specialized institutions. During the ERC Starting Grant program ER-HSP (GA – 311149), we have shown that this model presents both motor and cognitive impairments. We also identified accumulation of some lipid species in lysosomes as a putative therapeutic target to prevent neurodegeneration in this model. With the proof of concept grant, we plan to perform a preclinical trial to identify a possible treatment for this pathology. We have identified two different strategies to decrease the accumulation of lipids in neurons. In vitro assays have shown that both strategies can decrease accumulation of lipids in lysosomes. Importantly, both strategies can be translated into clinical trial in collaboration with industrial partners and represent potential new orphan drugs.

Mots-clés : therapy,orphan drug,preclinical trial
Projet ERC : HETEROPOLITICS (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : University of London — Pays : Royaume-Uni — Rôle : Partner
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 43593.75 €

Heteropolitics is a project in contemporary political theory which purports to contribute to the renewal of political thought on the ‘common’ (communities and the commons) and the political in tandem. The common implies a variable interaction between differences which communicate and collaborate in and through their differences, converging partially on practices and particular pursuits. The political pertains to processes through which plural communities manage themselves in ways which enable mutual challenges, deliberation, and creative agency. Since the dawn of the 21st century, a growing interest in rethinking and reconfiguring community has spread among theorists, citizens and social movements (see e.g. Esposito 2013; Dardot & Laval 2014; Amin & Roberts 2008). This has been triggered by a complex tangle of social, economic and political conditions. Climate change, economic crises, globalization, increasing migration flows and the malaise of liberal democracies loom large among them. These issues are essentially political. Rethinking and refiguring communities goes hand in hand thus with rethinking and reinventing politics. Hence ‘hetero-politics’, the quest for another politics, which can establish bonds of commonality across differences and can enable action in common without re-enacting the closures of ‘organic’ community or the violence of transformative politics in the past. Heteropolitics will seek to break new ground by combining an extended re-elaboration of contemporary political theory with a more empirically grounded research into alternative and incipient practices of community building and self-governance in: education; the social economy; art; new modes of civic engagement by young people; new platforms of citizens’ participation in municipal politics; network communities, and other social fields (Relevant cases include Sardex, a community currency in Sardinia; Barcelona en Comú, a citizens’ platform governing the city of Barcelona, etc.)

Mots-clés : community,commons,the political,infrapolitics,heteropolitics
Projet ERC : PARENTIME (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 724438.59 €

High socio-economic status parents consistently produce high socio-economic status children. The question is how. The objective of PARENTIME is to develop new socio-economic theories that unpack the detailed mechanisms driving the inter-generational transmission of inequality. Because of data limitations and theoretical traditions, the literature has focused on a narrow conceptualization of parental time (limited to the quantity of time spent with children in different kinds of activities), and a narrow set of child outcomes (limited to educational outcomes and socio-behavioral outcomes during the early years). Thus, while the results from this literature are informative at documenting the phenomenon of inter-generational transmission of human capital, they remain silent about the mechanisms underlying the process. PARENTIME aims to close this gap. In PARENTIME I will take a theoretically-driven Big Data approach by linking large representative 24-hour diary survey data of parents and children with very comprehensive and detailed information on child outcomes from administrative data to: First, go beyond the quantity of parental time to explore the inter-connections between family members and their role in the child’s acquisition of human capital (i.e., the timing and sequence, co-presence, multi-tasking, and instantaneous parental enjoyment). Second, establish long-term effects of parental time investments by looking at a comprehensive set of child human capital measures all the way into the child’s adult life. Third, arrive at a well-coordinated scientific approach, starting at the micro-sequential level of parents and children’s everyday life and building progressively to a macro understanding of the (re)production of socio-economic inequality.

Mots-clés : child development,intergenerational transmission of human capital,time use,household economics,parental time investments,human capital,quantitative methods
Projet ERC : EQFT (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

Highly-correlated many-body quantum states often emerge from correlations between strongly interacting electrons. The proposed research will experimentally explore emergent properties of quantum materials in the presence of strong correlations and spin-orbit coupling, when the spin and orbital angular momentum of electrons are strongly entangled. This is a largely experimentally unexplored regime where theoretical guidance suggests a fertile ground to potentially discover completely new types of correlated quantum behaviour, ranging from quantum spin liquids, where a local spin flip creates multiple exotic quasiparticles with fractional quantum numbers, to novel forms of magnetic order, with counter-rotating spin spirals or spontaneously formed periodic arrangements of spin vortices, to magnetic quasiparticles with topological properties. High applied magnetic fields will be used to stabilize novel magnetic phases with the potential to discover new universality classes for field-driven quantum phase transitions. Single crystals of spin-orbit dominated quantum materials, with key ingredients to exhibit correlated quantum behaviour, will be synthesized and their magnetic states will be probed using the latest advances in neutron and resonant x-ray diffraction and spectroscopy techniques that allow unprecedented high-sensitivity mapping of the static and dynamic correlations in space and time (or momentum and energy). The results will be compared with the latest theoretical models of many-body correlated quantum states with spin-orbit entanglement. This research will establish the experimental manifestation and manipulation of magnetic quasiparticles with topological character and help build a systematic understanding of the organizing principles that govern emergent quantum phases of matter in the unexplored regime of strong correlations and spin-orbit entanglement.

Mots-clés : frustrated magnetism,magnetic quantum phase transitions,kitaev materials