Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : NucEM (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Friedrich Miescher Institute — Pays : Suisse — Rôle : PI
Acronyme de l'entité : FMI
Type d'entité : Recherche
Financement ERC de l'entité : 2100929.0 €

Transcription factors (TFs) regulate gene expression and govern cell identity. In chromatinised genomes TF binding sites are frequently encapsulated in nucleosomes, which severely restrict access. While specialised pioneer factors have been proposed to bind to these sterically hindered sites, the exact mechanism by which these factors access nucleosomes remains unknown. A number of biochemical models have been put forward that would allow DNA sequence read-out, these include: (i) TFs compatible with the nucleosome architecture, (ii) alternative, partial, DNA motifs that render TFs nucleosome compatible, (iii) exposure of DNA binding sites through histone-nucleosome breathing dynamics, or (iv) remodelling of the histone core by TF binding. Despite being a fundamental question in genome regulation, no structural rationale is currently available for any of these proposed mechanisms. In unpublished work, we developed a novel biochemical assay allowing to simultaneously investigate all DNA registers on a nucleosome for TF access. This tool enabled us to solve the 3.8 Å structure OCT4/SOX2 bound to a nucleosome revealing the unexpected binding modes these TFs employ to engage nucleosomal binding sites (unpublished). Building on this novel biochemical workflow, we propose to solve additional structures of TFs compatible with the nucleosome-architecture and of those TFs suspected to bind to the ends of nucleosomal DNA. By dissecting multiple structures with diverse DNA binding domains in vitro and in cells, we wish to understand general principles of how DNA sequence motifs are being read-out at different sites on a nucleosome. The key questions we wish to address are: How does the location of a TF motif on a nucleosome impact affinity and/or the binding mechanism? Can TF binding remodel the nucleosome architecture? How do arrays of nucleosomes impact TF accessibility to DNA?

Mots-clés : transcription factors,nucleosome,nucleic acid,protein interactions
Projet ERC : Mini Brains (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : Austrian Academy of Sciences — Pays : Autriche — Rôle : PI
Acronyme de l'entité : OAW
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 150000.0 €

Transferring results from animal models to humans is a major bottleneck in pharmaceutical research. This is particularly true for brain disorders, including neurodegenerative and developmental diseases. Both animal models and conventional cell culture methods fail to recapitulate the complexity of the human brain and there are fundamental differences in developmental and physiological aspects between humans and the commonly used animal models. The high attrition rate of drugs for brain disorders has led major pharmaceutical companies to severely downsize their respective departments. To overcome the inherent limitations of current in vitro and in vivo models for brain disorders, we have generated a proprietary human pluripotent stem cell-derived 3D organoid culture system, termed cerebral organoids. These cerebral organoids are ‘mini brains’ that grow in a petri dish , display discrete but interconnected brain regions and recapitulate features of human brain development. ‘Mini Brains’ can be derived from patient-specific stem cells and represent a unique opportunity for creating specific human disease models in a 3D culture. The aim of the ‘Mini Brain’ project is to investigate the commercial feasibility of cerebral organoids as a new and highly cost-effective tool in the discovery and development of therapies for neurodegenerative and developmental diseases. The use of patient-specific cerebral organoids for drug screening and validation offers an alternative to animal experiments, reducing costs and animal use and improving reliability of results, and has the potential to decrease the cost of drug development, reduce the brain disease burden and increase the rate of approved drugs for brain disorders.

Mots-clés : cerebral organoids,3d culture,neurodegenerative disease,developmental disease,reduction of animal experiments
Projet ERC : DYNAMOX (Horizon 2020, appel 2015, Advanced 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 : 2482305.0 €

Transition metal (TM) oxides (TiO2, ZnO, NiO) are large gap insulators that have emerged as highly attractive materials over the past two decades for applications in photocatalysis, solar energy conversion, etc., all of which rely on the generation of charge carriers, their evolution and their eventual trapping at defects or a self-trapped excitons. Despite the huge interest for such materials, the very nature of the elementary electronic excitations (Frenkel, Wannier or charge transfer exciton) is still not established, nor is the way these excitations evolve after being created: excitonic polaron or charged polaron. Finally, the electron and hole recombine is also not clearly established because of issue of defects and trapping. In order to tackle these issues, here we implement novel experimental tools that would provide us with hitherto inaccessible information about the charge carrier dynamics in TM oxides. Of importance is the ability to detect both the electrons and the holes. Some of these tools have been developed in the PI’s group: i) Ultrafast X-ray absorption spectroscopy (XAS) will provide information about the final metal d-orbitals and about the structural changes around it; ii) Ultrafast X-ray emission (XES) will provide information about hole states. While these two approaches are ideal element-selective ones, the localization of the electron at metal atoms represents a small proportion of the electron population. Therefore, ultrafast Angle-resolved photoemission spectroscopy (ARPES) will be used to map out the band structure changes in the system and the evolution of the conduction band electrons. Ultrafast 2-dimensional (2D) UV (<400nm) transient absorption spectroscopy allows the mapping of the time evolution of both the valence and the conduction bands by its ability to pump and probe above the band gap. Last, Fourier Transform visible 2D spectroscopy will allow the probing of gap state dynamics at high time resolution.

Mots-clés : electrons,holes,band structure,charge trapping,surfaces,titanium dioxide,zinc oxide,nickel oxide,nanoparticles,single crystals
Projet ERC : DesignerPores (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
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 : 1936431.0 €

Translocation of ions and molecules is ubiquitous in biology and technology. Despite the tremendous amount of technical development, biological systems are still much more sophisticated in exerting exquisite control over active and passive translocation through nanopores in membranes than their existing synthetic mimics. This proposal aims to build novel designer nanopores that can match naturally evolved systems. For this we have to control all three stages of translocation: 1) diffusion and entry into, 2) diffusion in, and 3) exit from the nanopore. To gain fundamental insight into the translocation process we will employ microfluidic channels combined with holographic optical tweezers. Results from the microscale model system will be directly translated to nanoscale pores built with DNA origami nanotechnology. Our microfluidic experiments will automatically track diffusing spherical and non-spherical particles in artificial channels. Facilitated membrane transport will be mimicked by holographic optical tweezers providing full control over the translocation process. We will clarify how translocation depends on particle-particle, particle-channel, and particle-channel-entrance interactions. The generic principles discovered on the microscale will guide the design of artificial nanopores made by DNA origami self-assembly. Our DNA origami based designer nanopores will lead to a novel class of transporters for molecules, ions, and water through solid-state and lipid membranes. The project will generate a quantitative understanding of membrane transport processes, test existing theoretical models with unprecedented experimental control, and introduce a novel approach to design active and passive nanopores built from DNA.

Mots-clés : nanopores,dna origami,holographic optical tweezers,brownian motion,diffusion,translocation
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 Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1746741.77 €

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 : TIGITtherapy (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : Hebrew University of Jerusalem — Pays : Israël — Rôle : PI
Acronyme de l'entité : HUJI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Treating tumors with immune-related therapies is one of the most exciting and promising advancements made in the past decade. Cancer immunotherapy drugs have captured nearly 50% of the overall oncology drugs market. TIGIT is an important checkpoint inhibitory receptor discovered by our group in 2009. It is constitutively expressed by various immune cells and its expression is further increased on tumor infiltrating lymphocytes (TILs). TIGIT recognizes two main ligands, PVR and Nectin2 that are highly expressed on various tumors. Blockage of TIGIT on TILs either alone or in combination with another checkpoint inhibitory receptor, PD-1, leads to increased T and Natural Killer (NK) cell activity in vitro and inhibited tumor growth in vivo. We developed 9 different anti-TIGIT mAbs during my BacNK ERC advanced grant and previously. In the POC grant TIGITtherapy, which already attracted interest from several bio pharma companies, I propose testing which of the 9 anti-TIGIT mAbs and TIGIT-Ig are able to antagonize TIGIT activity.

Mots-clés : tigit,antibodies,tumors
Projet ERC : MONOSTAR (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : Johannes Gutenberg University Mainz — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2497500.0 €

Tree-rings are a key proxy archive for reconstructing high resolution climate variability over the past 1-2ka at regional to global scales. Skillful reconstructions require a stationary relationship between tree growth and climate (Hutton’s principle of uniformitarianism), which is commonly evaluated by statistical calibration/verification trials against instrumental measurements. This association, however, weakened during the second half of the 20th century, when tree-ring width and density chronologies from Northern Hemisphere forests were not able to track the rapidly increasing temperatures. This so-called “divergence” problem was identified in the 1990s to be a large-scale phenomenon, and not only questions the reliability of tree-ring based temperature reconstruction, but also affects our understanding of the Earth’s climate sensitivity to anthropogenic greenhouse gases. A conclusive explanation for this central problem of contemporary paleoclimate research is, however, still missing. Here, I propose to develop a process model that simulates year-to-year and long-term variations in both tree-ring width and density of different conifer species growing under different climate regimes. Evidence from this model will be combined with data from a new, hemispheric scale network of tree-ring width and density chronologies, as well as in-situ monitoring data, to train the model, validate synthetic timeseries, and analyze spatially varying influences of climatological, air chemical and ecological drivers on tree growth. Model-data fusion and inverse modelling techniques will be applied to quantify the non-linear mechanisms underlying divergence, and to deduce methodological recommendations that can be applied by any paleoclimatologist, working with different species and in different regions of the Northern Hemisphere, to mitigate late 20th century divergence and thus improve their climate reconstructions.

Mots-clés : dendrochronology,climate reconstruction,forward modeling,tree rings,northern hemisphere
Projet ERC : INCLUDE (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
Entité participante : University of Reading — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 232081.19 €

Tropical deforestation is an important contributor to climate change, through the release of significant amounts of carbon in the atmosphere. The main proximate cause of deforestation in tropical regions is agricultural expansion, followed by timber extraction. The general objective of this research is to understand how the interaction of technological, environmental, economic and social factors influence land use dynamics, including household decisions, about agricultural expansion and resource extraction in sensitive tropical regions. More specific questions relate to the role of various governance structures, particularly those recognizing common property regimes of land tenure to indigenous and rural communities, and the deliberative evaluation about the opportunity of reforming such structures in order to reduce deforestation and forest degradation. Although such aspects have been addressed in a variety of contexts, the approach proposed here is novel as a) it explicitly models the interaction between institutional, environmental, technological and socio-economic factors at different spatio-temporal scales, b) it specifically focuses on the governance structures associated with different land tenure regimes through the lenses of Social Network Analysis (SNA), c) uses a Q-methodology framework to develop a participatory approach to study stakeholders’ perspectives and attitudes on the necessary governance interventions to prevent deforestation and forest degradation and d) it assesses the relationships between agricultural expansion, deforestation, governance structures and stakeholders’ attitudes, with particular attention to the sensitivity of household land use decisions and resource extraction. In order to meet the research objectives, this project will focus on the province of Salta in the dry Chaco in North-Western Argentina, a region characterized by high rates of land cover change and the presence of indigenous/rural communities.
Projet ERC : TREECLIMBERS (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
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 : 1499375.0 €

Tropical forests are essential components of the earth system. Yet, much uncertainty exists about the exact role of this biome in the global carbon cycle. Our limited understanding of tropical forest functioning is reflected in uncertain global vegetation model projections. A large source of uncertainty in these models is their representation of ecosystem demographic processes. Interestingly, fieldwork has revealed lianas as important components of tropical forests, which are apparently increasing in abundance. Liana proliferation might be a key adaptation mechanism of tropical forests to climate change, which has potentially large impacts on the long term tropical forest biome carbon balance. Nevertheless, no single terrestrial ecosystem model currently includes lianas. TREECLIMBERS will generate important insights into the mechanisms by which lianas influence the carbon balance of tropical forests, by building the first vegetation model that includes lianas. We will make the first integrative study of (1) the contribution of lianas to instantaneous carbon and water fluxes, (2) liana contribution and influence on canopy structure, (3) their role for long term demographic processes, and (4) of their role in forest responses to drought events. TREECLIMBERS will develop the first liana plant functional type (PFT) by combining a unique global meta-analysis of existing data with innovative terrestrial LiDAR 3D measurements of the canopy to study the contribution of lianas to the canopy structure. New and available data will be integrated in the Ecosystem Demography (ED) model, a forerunner of the next generation of vegetation models. By using model-data fusion we will, for the first time, integrate the large amount of available and emerging liana data, leading to an integrated insight into the role of lianas in tropical forest functioning. This project aims to show that shifts in floristic composition due to global change may have important impacts in tropical forests.
Projet ERC : GLOBAL (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Institut de recherche pour le développement — Pays : France — Rôle : PI
Acronyme de l'entité : IRD
Type d'entité : Recherche
Financement ERC de l'entité : 1951307.0 €

Tropical rain forests (TRF) are the most species rich yet highly threatened ecosystems on Earth. They play pivotal roles as global climate regulators and for human wellbeing. Their long term conservation is central for global climate mitigation and biodiversity conservation. Elucidating the evolutionary processes that underpin this immense diversity is critical for improved conservation actions. What evolutionary processes determine TRF diversity? How will human-induced species losses impact the evolutionary history of TRF? Time calibrated phylogenies retain the fingerprint of these patterns and are fundamental prerequisites to maximize the conservation of evolutionary history. However, global densely sampled robust phylogenies are lacking for TRF plants, significantly limiting our ability to properly address these questions. I will generate the largest most comprehensive datasets ever assembled for a major, ecologically important and species-rich pantropical model plant family: Annonaceae (~2500 species). First, I will test major hypotheses about TRF evolution at a global scale and what biotic and abiotic factors drove their diversification. Then, I will predict the impact of plant species extinction on the evolutionary history of TRF. Using the extensive network of European herbaria, I will reconstruct a robust time-calibrated complete species level phylogenomic tree of Annonaceae. I will compile massive morphological, chemical and geographical datasets for all species. Novel paleoclimatic data will be modelled through space at ten discrete periods over the last 100 million years. These data will then be integrated using innovative statistical macroevolutionary comparative approaches to answer the above questions at never achieved levels of precision. GLOBAL will provide improved predictions of TRF evolution informing conservation policies, and set the new standard for next generation evolutionary studies of TRF evolution applicable to other key tropical groups.

Mots-clés : annonaceae,herbarium,next generation sequencing,tropical rain forest
Projet ERC : AcTafactors (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : Vlaams Instituut voor Biotechnologie — Pays : Belgique — Rôle : PI
Acronyme de l'entité : VIB
Type d'entité : Recherche
Financement ERC de l'entité : 149320.0 €

Tumor Necrosis Factor (TNF) is a homotrimeric pro-inflammatory cytokine that was originally discovered based on its extraordinary antitumor activity. However, its shock-inducing properties, causing hypotension, leukopenia and multiple organ failure, prevented its systemic use in cancer treatment. With this proof-of-concept study we want to evaluate a novel class of cell-targeted TNFs with strongly reduced systemic toxicities (AcTafactors). In these engineered immuno-cytokines, single-chain TNFs that harbor mutations to reduce the affinity for its receptor(s) are fused to a cell- specific targeting domain. Whilst almost no biological activity is observed on non-targeted cells, thus preventing systemic toxicity, avidity effects at the targeted cell membrane lead to recovery of over 90% of the TNF signaling activity. In this project we propose a lead optimization program to further improve the lead AcTafactors identified in the context of the ERC Advanced Grant project and to evaluate the resulting molecules for their ability to target the tumor (neo)vasculature in clinically relevant murine tumor models. The pre-clinical proof-of-concept we aim for represents a first step towards clinical development and ultimately potential market approval of an effective AcTafactor anti-cancer therapy.

Mots-clés : immuno cytokine,tumor vasculature,systemic toxicity