Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : chromo-SUMMIT (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical 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 : 1999815.0 €

Transient multivalent interactions are critical for biological processes such as signaling pathways controlling chromatin function. Chromatin, the nucleoprotein complex organizing the genome, is dynamically regulated by post-translational modifications (PTMs) of the chromatin fiber. Protein effectors interact with combinations of these PTMs through multivalent interactions, deposit novel PTMs, thereby propagate signaling cascades and remodel chromatin structure. To reveal the underlying molecular mechanisms, methods outside classical biochemistry are required, in particular due to the combinational complexity of chromatin PTMs and the transient supramolecular interactions crucial for their recognition. Here, we develop a novel approach, where we synthesize arrays of chemically defined designer chromatin fibers and use dynamic multiplex single-molecule imaging to dissect multivalent signaling processes in chromatin. Our studies target a key pathway, the DNA damage response (DDR), which regulates DNA repair processes central to cell survival and is critically implicated in cancer. Detailed knowledge is of utmost importance to develop targeted therapeutic interventions. We thus employ advanced peptide and protein chemistry to generate libraries of chromatin fibers of a defined PTM state that is encoded in the chromatin DNA. With the library immobilized in a flow cell, we use single-molecule detection to directly observe signaling processes by key DDR effectors in real time. Subsequent in situ polony decoding allows the identification of each chromatin fiber’s modification state, enabling broad sampling of signaling outcomes. Finally, we use dynamic computational models to integrate the effector-chromatin interaction network and test key mechanisms in cancer-based cell culture. Together, these methods will yield fundamental insight into chromatin and DDR signaling and will be of broad use for chemical and biomedical research with applications beyond the chromatin field.

Mots-clés : multivalency,peptide and protein synthesis,chromatin,nucleic acids,dna damage and repair
Projet ERC : CDK6-DrugOpp (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Veterinary Medicine Vienna — Pays : Autriche — Rôle : PI
Acronyme de l'entité : VUW
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2497520.0 €

Translational research aims at applying mechanistic understanding in the development of "precision medicine", which depends on precise diagnostic tools and therapeutic approaches. Cancer therapy is experiencing a switch from non-specific, cytotoxic agents towards molecularly targeted and rationally designed compounds with the promise of greater efficacy and fewer side effects. The two cell-cycle kinases CDK4 and CDK6 normally facilitate cell-cycle progression but are abnormally activated in certain cancers. CDK6 is up-regulated in hematopoietic malignancies, where it is the predominant cell-cycle kinase. The importance of CDK4/6 for tumor development is underscored by the fact that the US FDA selected inhibitors of the kinase activity of CDK4/6 as "breakthrough of the year 2013". Our recent findings suggest that the effects of the inhibitors may be limited as CDK6 is not only involved in cell-cycle progression: ground-breaking research in my group and others has shown that CDK6 is involved in regulation of transcription in a kinase-independent manner thereby driving the proliferation of leukemic stem cells and tumor formation. We have now identified mutations in CDK6 that convert it from a tumor promoter into a tumor suppressor. This unexpected outcome is accompanied by a distinct transcriptional profile. Separating the tumor-promoting from the tumor suppressive functions may open a novel therapeutic avenue for drug development. We aim at understanding which domains and residues of CDK6 are involved in rewiring the transcriptional landscape to pave the way for sophisticated inhibitors. The idea of turning a cancer cell's own most potent weapon against itself is novel and would represent a new paradigm for drug design. Finally, the understanding of CDK6 functions in tumor promotion and maintenance will also result in better patient stratification and improved treatment decisions for a broad spectrum of cancer types.

Mots-clés : cdk6,transcription,oncology,tumor suppressor,new principles in drug development,targeted therapy,precision medicine,leukemia,rime
Projet ERC : GLASST (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : CERCA Institution — Pays : Espagne — Rôle : Partner
Acronyme de l'entité : CERCA;I-CERCA
Type d'entité : Recherche
Financement ERC de l'entité : 29750.0 €

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 : GLASST (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : University of Chicago — Pays : Etats-Unis — Rôle : Partner
Acronyme de l'entité : UC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 35632.0 €

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 : T6S (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
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 : 1751853.0 €

Transporting selected proteins across the cell envelope in a controlled manner is a fundamental property of all cell types. For bacteria, secretion systems play a central role in the translocation of effectors that mediate interactions with other cells. The bacterial Type VI Secretion (T6S) system is one of the most widespread secretion systems and, in a cell-cell contact-dependent fashion, it injects effectors into eukaryotic and bacterial targets. The T6S system utilizes a cytoplasmic phage tail-like apparatus that is anchored to the cell envelope. A contractile sheath propels a macromolecular effector-loaded tube/spike-complex outside the cell and into the target. Here, we will establish a model of T6S-mediated cell-cell interactions by integrating information from the molecular, cellular and intercellular scales. The model will reveal answers to three paramount questions of the field: Aim 1 (molecular scale) will elucidate an atomic model of the T6S membrane-anchoring complex in loaded and fired conformational states. Aim 2 (cellular scale) will identify the mechanisms and relevance of clustering multiple T6S machines in a confined region of the cell. Aim 3 (intercellular scale) will resolve T6S actively engaged in cell-cell interactions to clarify the in vivo structure and significance of the inner tube in effector translocation and target cell penetration. Electron cryo-tomography (ECT) will be used as the key technique to resolve unique structures in their cellular context, in a native state, in three dimensions and at the crucial nanometer-to-micrometer range. Cryo-focused ion beam milling will be established to prepare samples thin enough for ECT imaging. ECT data will be complemented by high-resolution structural information of sub-complexes (in vitro) and low-resolution fluorescence light microscopy data on dynamics (in vivo). In the future, our approach will prove useful to study other types of bacterial cell-cell interactions.

Mots-clés : bacterial cell biology,cell cell interactions,protein secretion,cryo electron microscopy,tomography,sub tomogram averaging,focused ion beam milling,fluorescence light microscopy,phage tail
Projet ERC : TE_INVASION (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : University of Liverpool — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1991315.0 €

Transposable elements play major roles in the genome evolution of eukaryotes, and cause harmful mutations, deleterious side effects, and disease. These costs drive their eukaryotic hosts to evolve counter-adaptations, which are so effective that TEs are thought to only survive long term by invading new naïve species. These transposable element invasions appear to occur via horizontal transfer, and can result in the rapid, selfish spread of the element through a species. Despite the evolutionary importance of the host-transposable element relationship, there are still major gaps in our knowledge of how they evolve and persist. Host resistance can evolve astonishingly rapidly, but the evolutionary mechanism by which this happens is unknown. Some horizontal transfer events result in successful invasions, but we have little idea of what factors favour success, or, except in rare cases, how the transfer events occur. This proposal outlines a four-part research programme to address these gaps, examining both sides of the coevolutionary equation. Specifically, I will examine the rapid evolution of suppression from the host side, to understand the population genetics of this process. I will study invasions from the perspective of the transposable element, and ask what genetic factors contribute to their success. To accomplish these objectives, I will take advantage of a unique opportunity-- an ongoing invasion of a model transposable element in a close relative of the genetic model fly. Finally, I will examine the role of parasites as vectors of TEs ,to understand mechanisms of horizontal transfer between species.

Mots-clés : transposable elements,drosophila
Projet ERC : PALADYN (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : Autonomous University of Barcelona — Pays : Espagne — Rôle : PI
Acronyme de l'entité : UAB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1475489.22 €

Tropical climates are changing rapidly in the most populated regions of the planet. The changes largely arise from alterations in the Hadley circulation driven by natural and anthropogenic factors, whose relative roles and temporal variability are unclear. These knowledge gaps are in part due to the shortage of methods to study the atmospheric circulation before the advent of instrumental and satellites observations, and compounded by the contradictions between models and palaeo-data. The aim of the project is to develop an innovative palaeo-proxy approach to investigate the natural range of variability of the Hadley circulation during past episodes of extreme warmth and cold. The approach relies on the exploitation as climate proxy of an untapped but widespread material in marine sediments: windborne pyrogenic carbon (PyC) derived from savannah and grassland fires in the tropics. Through the geochemical and isotopic spatial characterization of PyC, along with the analysis of mineral dust in the modern tropical deep ocean, and a PyC biogeochemical model, we will build an interpretative framework of PyC deposition in deep-sea sediments. Its application in Pliocene-Pleistocene sequences from the Atlantic and the Pacific will allow the reconstruction of past meridional and zonal shifts in the Intertropical Convergence Zone and the Southern hemisphere westerlies, and provide new constraints on the natural variability of the Hadley circulation and associated hydroclimates. PALADYN is possible thanks to the combination of cutting-edge geochemical and satellite data, and GIS methodologies, with in-depth interdisciplinary expertise on the palaeoclimatic study of marine sediments. We will provide new important datasets of windborne deep-sea PyC for testing and refining prediction models of atmospheric circulation, carbon cycle, precipitation and wildfires, issues which are of paramount global importance from scientific as well as societal standpoints.

Mots-clés : hadley circulation,atmospheric circulation,hydroclimate,climate proxy,pyrogenic carbon,biomarker,stable isotopes,biomass burning aerosols,bpca,pleistocene,pliocene,wildfire,itcz,southern hemisphere westerlies,high pressure ridge,easterlies,palaeoceanography
Projet ERC : FORESTPOLICY (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 990540.75 €

Tropical forests are critical for human wellbeing through their contributions to climate stability, biodiversity conservation, food production, and rural livelihoods. Despite numerous global commitments to help conserve and restore tropical forests, these areas are disappearing faster than ever. The goal of this research is to provide major advancements in our understanding of the conditions under which forest-focused supply chain policies (FSPs), a form of voluntary environmental governance, can lead to improved conservation and livelihoods in the tropics. My proposal overcomes major methodological limitations of past work through four major innovations: i) a coordinated pan-tropical analysis of multiple forest-risk commodities, ii) simultaneous examination of conservation and livelihood outcomes, iii) a focus on mechanisms of impact, not just measures of impact, and iv) comparative study with triangulation across multiple scales and methods. I will examine the importance of four key contextual factors in determining FSP effectiveness: i) the degree of public sector involvement in the governance of land use behaviors in the target regions; ii) historical land use trends in the target regions; iii) supply chain arrangements for the targeted commodities; and iv) values of the targeted populations. Additionally, I examine how the type of implementation mechanism used (i.e., whether the firm immediately suspends non-compliant producers) interacts with these contextual factors in determining the effectiveness and equity of FSPs. By identifying the conditions under which different types of FSPs and related implementation mechanisms can deliver improved conservation and livelihood outcomes, the resulting analysis will provide urgently needed policy recommendations to companies and other policy makers for how to better tailor the design of FSPs to specific contexts.

Mots-clés : supply chain,forest,food,voluntary environmental policy,corporate sustainability,conservation,livelihood
Projet ERC : PANTROPOCENE (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : Australian National University — Pays : Australie — Rôle : Partner
Acronyme de l'entité : ANU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 137043.75 €

Tropical forests are globally recognised as biodiversity hotspots and environments that are crucial for climate regulation, landscape stability, and the carbon cycle. Local deforestation can have regional and global feedbacks and 20th-21st century human actions in tropical forests are seen as a key part of the ‘Anthropocene’ – or the anthropogenic domination of earth systems. It remains an open question, however, as to whether pre-industrial human impacts on these environments had similar earth systems effects. 15th to 18th century European colonial empires drew together long-separated Old and New World ecologies, with implications for species distributions, demography, and land management in the tropics. This followed millennia of indigenous activities with possible regional and global cumulative results. Yet, we have no concrete understanding of how pre-industrial impacts varied spatially and temporally, what they meant for local sustainability, and how they compare to modern human impacts. The PANTROPOCENE Project addresses these questions by taking the Spanish Empire as a frame of reference for using archaeological, historical, and palaeoenvironmental data to build ‘pan-tropical’ spatial characterisations of pre-colonial, colonial, and industrial land-use. Undertaking novel palaeoecological and landscape survey fieldwork in the Philippine Archipelago, the often-neglected centre of the Spanish East Indies, the project will bring new data together with existing records, notably from the Neotropics, to ensure full tropical coverage of the Spanish Empire. The results will be factored into climate, geomorphological, and atmospheric models to determine how changing pre-industrial technology, subsistence, and administration had regional and global feedbacks on occupied human environments, informing understandings of the pace and threat of contemporary land-use changes in the context of endemic Island Southeast Asian biodiversity and the tropics more broadly.

Mots-clés : anthropocene,tropical forest prehistory and history,archaeology,spanish empire,columbian exchange,pre industrial land use