Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : COSMICLENS (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe sciences
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 : 2431884.0 €

Measuring cosmological distances has revolutionized our understanding of the Universe, and is still doing so! Early work in the 1920s led to the discovery of the expansion of the Universe. More precise distance measurements in the 90s with type-Ia supernovae revealed that this expansion is accelerating, with crucial consequences in cosmology and physics. Is the acceleration due to some repulsive form of dark energy? To Einstein's cosmological constant? Do we need to consider new physics? Answering these fundamental questions requires a precise measurement of the Hubble parameter, H0, which is my goal using the time delay (TD) method in strongly lensed quasars. The TD method exploits well-known physics on galaxy-scales. It is one of the very few techniques that can yield H0 to <2% using a single methodology. It involves no calibration, and is truly independent of any other cosmological probe. Capitalizing on the successful pathfinders COSMOGRAIL (PI: Courbin) and H0LiCOW (PI: Suyu, CoI: Courbin) time has come to fully exploit TDs with an observational, modeling and technical boost, organized in 2 phases. Phase I will secure H0 to 2% using the current chain of analysis, with feasible enhancements beyond the current state-of the-art. This will confirm or refute the tension seen between H0 values with different cosmological probes. Phase II targets 1% precision, improving the FoM of Stage-IV cosmological surveys by 40%. The 4 proposed Work Packages can transform the field within the next 5 years by 1- implementing the first high-cadence photometric monitoring of lensed quasars to measure 50 new TDs, 2- providing new flexible non-parameteric lens models based on sparse regularization of the reconstructed source and lens mass/light distributions, 3- providing a modular end-to-end simulation framework to mock lensed systems from hydro-simulations and to evaluate in detail the impact model degeneracies on H0, 4- discovering new suitable lensed quasars in current surveys.
Projet ERC : TopMechMat (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
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 : 1999264.0 €

Mechanical metamaterials are man-made structures with tailored vibrational properties geared towards applications such as earth-quake protection, energy harvesting, or medical imaging. Recently, we promoted a new design principle for such materials: topological band-theory known from quantum condensed matter physics. To date, the use of topology in mechanical materials has been largely restricted to one or two dimensions, a central shortcoming for applications. The objective of TopMechMat is to address this challenge (i) by establishing a theoretical framework for topological mechanical metamaterials in three dimensions, (ii) by developing a novel algorithm enabling the sample design, and (iii) by experimentally validating the proposed materials. The current approach to topological mechanical systems is based on lcoal symmetries unnatural to classical mechanics. Crystalline symmetries, on the other hand, are ubiquitous in metamaterials and are known to stabilize topological phases. Using group cohomology techniques we will establish a theoretical framework for topological phonons in three dimensions. Translating a theoretical model into an actual sample requires extensive finite element simulations. However, the complexity of topological phonon models precludes the application of known design algorithms. We plan to use a neural network to address this challenge. This will allow us to exploit the power of genetic algorithms in executing the required large-scale parameter scans. The successful implementation of this design algorithm will present us with an exciting opportunity: Mechanical systems might enable the discovery of yet unobserved topological phases of matter. We plan to build a three-axis scanning vibrometer to investigate additively manufactured metamaterial samples. This will allow us to validate our ideas and to provide proof-of-principle results emphasizing the feasibility of our designs for concrete applications.

Mots-clés : metamaterials
Projet ERC : UNEXPECTED (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Lund University — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Mechanisms of self-renewal in hematopoietic stem cells (HSCs) have been subject to intense studies during the last decades. However, this is still a poorly defined process and very limited progress has been made in the long sought goal of expanding HSCs ex vivo to allow for critical improvements of bone marrow transplantation procedures for cancer patients and potentially a broader use of HSCs in gene therapy and regenerative medicine. The aim of this research program is to systematically identify and characterize regulators of self-renewal in human HSCs and to develop strategies for stem cell expansion. Within the project we will develop novel paradigms for CRISPR (clustered regularly interspaced short palindromic repeats) mediated gene editing in primary human HSCs to enable detailed assessment of gene function. We will further employ forward genetic screening approaches based on both CRISPR/Cas9 gene editing and RNA interference (RNAi) gene silencing to identify regulators of renewal and differentiation in human HSCs. Large numbers of HSCs will be targeted with genome-wide lentiviral CRISPR (sgRNA) and short hairpin RNA (shRNA) libraries. Screening assays for HSC self-renewal will be evaluated in a pooled format and de-convoluted using next generation sequencing, allowing thousands of perturbations to be assayed in parallel. Candidate genes from the screens will be studied further using genetic barcoding and transplantations assays in immundeficient mice to test whether they can be targeted to induce expansion of HSCs ex vivo. Finally, based on our findings, we aim to develop GMP compatible conditions for HSC expansion in preparation for clinical trials involving expansion of umbilical cord blood derived stem cells to treat patients with acute leukemia.

Mots-clés : hematopoiesis,transplantation,crispr,cas9,stem cell expansion,genetic barcoding
Projet ERC : MECHANOGENOMICS (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Aix-Marseille Université — Pays : France — Rôle : PI
Acronyme de l'entité : amU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1184538.0 €

Mechanotransduction is the signaling by which external mechanical stimuli are converted into biological signals within the cell. It helps to probe and map the rigidity and texture of external world and appeared with the first life forms some 3.8 billion years ago. In mammals, many fundamental physiological functions are regulated by mechanotransduction. The somatosensory system is involved in the perception of touch, pain and proprioception. Molecular mechanosensors of this sensory system are mechanically-activated ion channels. These channels are expressed at the nerve endings of sensory neurons that project long axons to the skin and to deeper body structures. The identification of these channels constitutes one of the most important challenges in the field of sensory transduction. So far only one gene family has been unambiguously associated with mammalian mechanosensory function and is specifically involved in light-touch sensation. Therefore, the identity of mechanotransduction channels involved in the detection of other mechanosensory modalities including proprioception and mechanical pain remain to be determined. We will combine patch-clamp methodology and single-cell transcriptome sequencing to generate the specific expression profile of distinct populations of mouse mechanosensitive neurons. Combination of bioinformatics, expression analysis and electrophysiological approaches will be used to identify molecular components of mechanotransduction channels. We will explore the role of identified genes in somatosensory functions. The long-term objective is to provide a compelling view of mechanosensitive process diversity in mammalian somatosensation through molecular identification of mechanotransduction channels and characterization of their physiological functions in touch, pain and proprioception. This proposal will also provide novel channel candidates that may be involved other mechanosensory functions such as embryogenesis, bone development and hearing.

Mots-clés : mechanotransduction,ion channel,somatosensation
Projet ERC : Deep4MI (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer science and informatics
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 : 2499900.0 €

Medical imaging has revolutionized medicine and healthcare like no other recent technology, and is now an integral part of diagnosis, treatment planning, treatment delivery and follow-up. It provides an unparalleled ability to image anatomy and function with high spatial (and temporal) resolution. Its success has led to a dramatic increase in the number of medical imaging examinations. Despite this success, medical imaging is often stressful for patients, requires patient cooperation and is difficult in the presence of motion (e.g. patient motion or breathing motion). Furthermore, even more than 100 years after the discovery of X-rays, the interpretation of medical images relies almost exclusively on human experts. All of the above mean that there is a strong need for increased automation and quantification in order to reduce costs, increase efficiency and patient-friendliness, and provide higher diagnostic and prognostic accuracy for clinical decision making. At the same time, machine learning and deep learning techniques have made significant advances and have started to make a large impact in many real-world applications. The aim of this proposal is to exploit these advances to address the above challenges and to achieve a paradigm shift in the way information is extracted from medical images for diagnostics, therapy and follow-up. We will do this by developing a transformative and synergistic approach to medical imaging in which acquisition, reconstruction, analysis and interpretation will be tightly coupled, with bidirectional feedback between the different stages, in order to optimize the overall objective of the imaging pipeline: Extracting clinically useful and actionable information. To achieve this step change, the project aims to develop novel deep learning approaches for image acquisition, reconstruction, analysis and interpretation that can be trained in an end-to-end fashion, allowing fast and more efficient imaging.

Mots-clés : deep learning,medical image computing
Projet ERC : HealthScaping (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : University of Amsterdam — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UvA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1998004.0 €

Medieval public health is mired in modern myth: without centralized governments, democratic values and advanced medicine, promoting health at the population level was purportedly either unthinkable or simply impractical. Offering a radically different view, HealthScaping will document, analyze and disseminate knowledge about preventative public healthcare between 1200-1500, an era of accelerated urbanization followed by massive demographic decline, with the onset of Black Death (1347-51). This long-term and comparative perspective will fundamentally revise the narrative of European public health by tracing the development and impact of pertinent government policies, medical discourses and social and religious action in the continent’s two most urbanized and richly documented regions, Italy and the Low Countries. The project taps numerous written, material and visual sources and archaeological data from several sites, and examines them also by critically engaging the insights of governmentality studies, cultural-spatial analysis and actor-network theory. A multidisciplinary team, working in a Geographical Information Systems environment and generating innovative urban health maps, will recover earlier societies’ struggles with domestic and industrial waste, travel and labor hazards, food quality, and social and religious behaviors considered harmful or dangerous. As such, the project’s implications will be broad and profound, for it will 1) dislodge bio-power from its accustomed place in modernity; 2) historicize the concept of the public sphere from a health perspective; and 3) challenge the privileged role given to epidemic disease as a catalyst for environmental interventions in premodernity. It will also 4) generate new insights for public health scholars and practitioners working today around the globe, by rethinking the feasibility of preventative interventions under highly diverse forms of government, culture and topography.

Mots-clés : urban history,public sphere,modern divide
Projet ERC : MELASTOP (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : University of Padua — Pays : Italie — Rôle : PI
Acronyme de l'entité : UNIPD
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Melanoma is the most aggressive skin tumor, extremely difficult to treat and with high mortality rate. Overcoming reduced sensitivity and acquired resistance to targeted therapy is a major goal of current melanoma research. Therefore, there is an urgent need for development of novel drugs that can cure and prolong the survival of melanoma patients. Molecular targeted therapy by using a drug that reduces the growth and spread of cancer cells via inhibition of specific protein or pathway is a milestone of precise medicine and treatment. Recent observations demonstrate that BRAF and MEK inhibitors induce increased reactive oxygen species (ROS) in melanoma and as a consequence tumor cells activate adaptive antioxidant mechanisms to keep their cellular redox state below a deadly threshold. Thus, it has been proposed that removal of antioxidant could be exploited for therapeutic benefits. In our ERC Consolidator grant RENDOX we have characterized the mevalonate metabolic pathway and discovered that this metabolic pathway as well as its enzyme, UBIAD1, have antioxidant properties and are critical caretakers of oxidative stress and ferroptosis in pathological conditions, such as melanoma progression. The MELASTOP project is grounded on the validation and repositioning of pre-existing inhibitors, such as statins and parabens derivatives (UBIAD1i) as novel therapeutic drugs to treat melanoma resistance, which represents an extraordinary opportunity to improve the current limitation. The current ERC PoC proposal aims at lead optimization, preclinical validation, IPR positioning, marker assessment and other commercial activities including go to market strategy and dialogue with potential collaborators of these mevalonate and UBIAD1 inhibitors. We envision that this PoC represents a unique medical and commercial opportunity to treat and cure BRAF-resistant melanoma patients in urgent need of new treatment options.

Mots-clés : ubiad1,antioxidant,cancer progression,statins,melanoma
Projet ERC : METALERT-STOP (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Spanish National Cancer Research Centre — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CNIO
Type d'entité : Recherche
Financement ERC de l'entité : 2497945.0 €

Melanomas are the only tumors where lesions barely over one millimeter in depth can be at risk for metastasis. An increasing number of (epi)genetic alterations and mechanisms of immune evasion have been identified in this disease. Nevertheless, no molecular biomarker has been approved as a bona fide prognostic indicator. Progress in this field has been hampered by the paucity of models to visualize premetastatic niches in vivo, and monitor relapse after surgery. We have overcome these limitations by generating reporter mouse strains to “illuminate” premetastatic niches. Specifically, our “MetAlert” mice were designed for whole-body imaging of the aberrant expansion of the lymphatic vasculature, an early event that precedes metastasis. MetAlert, together with functional studies in human cells and histopathological validation in clinical biopsies, revealed the growth factor MIDKINE as a new melanoma-secreted prometastatic driver. We have now discovered roles of MDK as an immune suppressor, and identified a MDK-associated transcriptional profile that separates patients with a distinct expression of alarmins and bacterial response factors. Proteomic analyses revealed a set of additional factors secreted by aggressive melanoma cells, but their specific contribution to premetastatic niches is unclear. Here we will exploit our MetAlert and novel imaging reporters we have generated for a comprehensive spatio-temporal and functional analysis of premetastatic niches in vivo (including and beyond MDK). We will define how melanomas act “at a distance” before metastasis (Aim 1), and evade the immune system at different anatomical sites (Aim 2). Aim 3 will dissect the impact of the microenvironment, particularly via alarmins. Aim 4 will pursue the therapeutic targeting of metastatic niches (pre and post-surgery) with immunomodulators we discovered (and have led to clinical trials), and by targeting vulnerabilities that we found distinguish melanoma from other diseases.

Mots-clés : melanoma,immunotherapy,immuno tolerance,tumor biomarkers,metastasis
Projet ERC : CASSANDRA (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : University of Fribourg — Pays : Suisse — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1989181.0 €

Meltwater running off the flanks of the Greenland ice sheet contributes roughly 60% to its mass loss, the rest being due to calving. Only meltwater originating from below the elevation of the runoff limit leaves the ice sheet, contributing to mass loss; melt at higher elevations refreezes in the porous firn and does not drive mass loss. Therefore any shift in the runoff limit modifies mass loss and subsequent sea level rise. New evidence shows surface runoff at increasingly high elevations, outpacing the rate at which the equilibrium line elevation rises. This research proposal focuses on the runoff limit as a powerful yet poorly understood modulator of Greenland mass balance. We will track the runoff limit over the full satellite era using two of the largest and oldest remote sensing archives, Landsat and the Advanced Very High Resolution Radiometer (AVHRR). We will establish time series of the runoff limit for all regions of Greenland to identify the mechanisms driving fluctuations in the runoff limit. This newly gained process understanding and a wealth of in-situ measurements will then be used to build firn hydrology models capable of simulating runoff and the associated runoff limit over time. Eventually, the firn hydrology models will be applied to reconcile estimates of Greenland past, present and future mass balance. Covering the entire satellite era and all of Greenland, the focus on the runoff limit will constitute a paradigm shift leading to major advance in our understanding of how vulnerable the surface of the ice sheet reacts to climate change and how the changing surface impacts runoff and thus Greenland's role in the global sea level budget.
Projet ERC : EcoLipid (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : University of Warwick — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1965113.75 €

Membrane lipids form the structural basis of all cells. In bacteria Escherichia coli uses predominantly phosphorus-containing lipids (phospholipids) in its cell envelope, including phosphatidylethanolamine and phosphatidylglycerol. However, beyond E. coli a range of lipids are found in bacterial membranes, including phospholipids as well as phosphorus (P)-free lipids such as betaine lipids, ornithine lipids, sulfolipids and glycolipids. In the marine environment, it is well established that P availability significantly affects lipid composition in the phytoplankton, whereby non-P sulfur-containing lipids are used to substitute phospholipids in response to P stress. This remodeling offers a significant competitive advantage for these organisms, allowing them to adapt to oligotrophic environments low in P. Until very recently, abundant marine heterotrophic bacteria were thought to lack the capacity for lipid remodelling in response to P deficiency. However, recent work by myself and others has now demonstrated that lipid remodelling occurs in many ecologically important marine heterotrophs, such as the SAR11 and Roseobacter clades, which are not only numerically abundant in marine waters but also crucial players in the biogeochemical cycling of key elements. However, the ecological and physiological consequences of lipid remodeling, in response to nutrient limitation, remain unknown. This is important because I hypothesize that lipid remodeling has important knock-on effects restricting the ability of marine bacteria to deal with both abiotic and biotic stresses, which has profound consequences for the functioning of major biogeochemical cycles. Here I aim to use a synthesis of molecular biology, microbial physiology, and "omics" approaches to reveal the fitness trade-offs of lipid remodelling in cosmopolitan marine heterotrophic bacteria, providing novel insights into the ecophysiology of lipid remodelling and its consequences for marine nutrient cycling.

Mots-clés : lipid remodelling,biogeochemical cycles,marine heterotrophic bacteria,roseobacters,sar11,fitness trade off