Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : MicroC (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Bocconi University — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 455977.5 €

The occurrence of therapeutic resistance is a major cause for the small effect on overall survival showed by targeted cancer therapies. Whilst experimental strategies to evaluate available treatments have been faced by an ever increasing number of possible combinations, computational approaches have been challenged by the lack of a framework able to model the multiple interactions encompassed by the three major factors affecting therapeutic resistance: selection of resistant clones, adaptability of gene signalling networks, and a protective and hypoxic tumour microenvironment. Here I propose a novel modelling framework, Agent-Based Modelling of Gene Networks, which brings together powerful computational modelling techniques and gene networks. This combination allows biological hypotheses to be tested in a controlled stepwise fashion, and it lends itself naturally to model a heterogeneous population of cells acting and evolving in a dynamic microenvironment, which is needed to predict therapeutic resistance and guide effective treatment selection. Using triple negative breast cancer (TNBC) as a testing case (15% of breast cancers, lacks validated), I propose to: 1. Develop a computational model of the TNBC tumour microenvironment using in-vitro and in-vivo, including patient-derived, models and data from clinical samples. 2. Validate the ability of the model to predict driver genes conferring a survival advantage to cancer cells in a hypoxic microenvironment. 3. Predict combinations of druggable targets to tackle TNBC therapeutic resistance. 4. Select most effective drug combinations and validate pre-clinically. This project will deliver pre-clinically validated drug combinations, new therapeutic targets and a virtual environment to study individual tumours and predict therapeutic resistance. Complementing and empowering experimental models and assays, microC will offer a new powerful tool for diagnosis and therapy.
Projet ERC : TERIFIC (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : National Oceanography Centre — Pays : Royaume-Uni — Rôle : Partner
Acronyme de l'entité : NOC
Type d'entité : Recherche
Financement ERC de l'entité : 1166998.98 €

The ocean Meridional Overturning Circulation (MOC) is responsible for poleward heat transport, and deep storage of heat and carbon. Climate models generally predict that a slowdown of the MOC will occur this century, with dramatic regional and global climate changes, but how the slowdown will occur is subject to debate. It is widely recognised that convection -- the downward limb of the MOC -- is sensitive to freshwater fluxes, and recent investigations have suggested that the increased melt from the Greenland Ice Sheet has already reduced convection. Yet in 2015, convection returned, and was anomalously strong. Despite the expectation that the MOC is sensitive to freshwater forcing, we do not understand the processes by which freshwater inputs influence the MOC. The two key gaps in our understanding are: how freshwater reaches the regions of deep convection, and the relative importance of freshwater to convection and restratification. Numerical simulations give conflicting results on freshwater pathways, and convective parameterisations neglect small-scale restratifying processes. Traditional observational approaches cannot capture the spatial and temporal variability of these processes without inordinate cost. TERIFIC addresses these gaps in understanding through new observations, leveraging recent advances in small-scale electronics to deploy large numbers of mini-drifters on the shelves of Greenland, and employing subsurface and surface autonomous platforms to characterise the balance of processes controlling convection and restratification. The analysis of these observations will answer fundamental questions about how freshwater reaches and affects the regions of deep convection, and enable a critical ground truth of numerical simulations of these processes for climate models.

Mots-clés : deep convection,meridional overturning circulation,freshwater fluxes,greenland ice sheet,autonomous underwater vehicles,ocean surface drifters
Projet ERC : Myel-IN-Crisis (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
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 : 2500000.0 €

The oligodendrocyte, the largest cell in mammalian biology, greatly enables central nervous system (CNS) function through production of a single substance: myelin. Oligodendrocytes undergo a dramatic 1-2 day metamorphosis during myelination, increasing their cell surface area ~6500-fold with proteolipid extensions to nerve axons in the CNS white matter. How is this synthetic feat accomplished? We lack a comprehensive understanding of machinery that precisely coordinates transcription, translation, lipid synthesis and energy production. Moreover, how do these mechanisms become so intensively upregulated during myelination? Does this extraordinary transient state put the myelinating oligodendrocyte at risk of death in diseases of white matter? These questions underlie the Aims of the proposal “Myel-IN-crisis.” I propose (Aim 1) testing whether an “Integrated Synthetic Programme (ISP)” controls oligodendrocyte differentiation, metabolic and synthetic requirements of developmental myelination. In Aim 2, I will investigate roles for “smart sensor” oxygen (HIF) and nutrient (mTOR) pathways in regulating initiation and termination of the ISP. During development, extrinsic white matter injury in preterm infants leads to cerebral palsy, while intrinsic defects in myelin protein PLP1 cause the fatal human leukodystrophy, Pelizaeus-Merzbacher disease (PMD). Preliminary studies indicate transcriptional and translational dysregulation in human PLP1-mutant oligodendrocytes, which become iron overloaded leading to apoptotic cell death. In Aim 3, I propose that either extrinsic (e.g., hypoxia) or intrinsic (e.g., PLP1 mutation) factors promote a “Universal Stress Response (USR)” in the pre-myelinating oligodendrocyte that leads to toxic dysregulation of the ISP. Finally, in Aim 4 we will identify the key pathways of the USR to generate strategies for rescue of myelination with potential translational impact in cerebral palsy and leukodystrophy, multiple sclerosis and stroke.

Mots-clés : oligodendrocytes,myelination,cns development,gene regulation,protein synthesis,hypoxia,hif signaling,pi 3k signaling,axon,leukodystrophy,cerebral palsy
Projet ERC : Lost Frontiers (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : University of Nottingham Ningbo China — Pays : Chine — Rôle : Partner
Acronyme de l'entité : UNNC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 33286.25 €

The only lands on Earth that have not been explored in any depth by science are those that have been lost to the oceans. Global warming at the end of the last Ice Age led to the inundation of vast landscapes that had once been home to thousands of people. These lost lands hold a unique and largely unexplored record of settlement and colonisation linked to climate change over millennia. Amongst the most significant is Doggerland. Occupying much of the North Sea basin between continental Europe and Britain it would have been a heartland of human occupation and central to the process of re-settlement and colonisation of north Western Europe during the Mesolithic and the Neolithic. Within this submerged landscape lies fragmentary yet valuable evidence for the lifestyles of its inhabitants including the changes resulting from both the encroaching sea and the introduction of Neolithic technologies. This inundated landscape cannot be explored conventionally, however pioneering work by the applicant’s research group has led to the rediscovery of Doggerland through the creation of the first detailed topographic maps relating to human occupation in the Early Holocene. Within this project world-leading innovators in the fields of archaeo-geophysics, molecular biology and computer simulation will develop a ground-breaking new paradigm for the study of past environments, ecological change and the transition between hunter gathering societies and farming in north west Europe. It will: 1) use the latest seismic reflectance data available to generate topographical maps of the whole of early Holocene Doggerland that are as accurate and complete as possible. 2) reconstruct and simulate the palaeo-environments of Doggerland using ancient DNA extracted directly from sediment cores. 3) explore the Mesolithic landscapes and also identify incipient Neolithic signals indicating early contact and development within the region of Doggerland.

Mots-clés : marine archaeology,palaeolandscapes,coastal shelf prehistoric research
Projet ERC : Lost Frontiers (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : University of Bradford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1834094.25 €

The only lands on Earth that have not been explored in any depth by science are those that have been lost to the oceans. Global warming at the end of the last Ice Age led to the inundation of vast landscapes that had once been home to thousands of people. These lost lands hold a unique and largely unexplored record of settlement and colonisation linked to climate change over millennia. Amongst the most significant is Doggerland. Occupying much of the North Sea basin between continental Europe and Britain it would have been a heartland of human occupation and central to the process of re-settlement and colonisation of north Western Europe during the Mesolithic and the Neolithic. Within this submerged landscape lies fragmentary yet valuable evidence for the lifestyles of its inhabitants including the changes resulting from both the encroaching sea and the introduction of Neolithic technologies. This inundated landscape cannot be explored conventionally, however pioneering work by the applicant’s research group has led to the rediscovery of Doggerland through the creation of the first detailed topographic maps relating to human occupation in the Early Holocene. Within this project world-leading innovators in the fields of archaeo-geophysics, molecular biology and computer simulation will develop a ground-breaking new paradigm for the study of past environments, ecological change and the transition between hunter gathering societies and farming in north west Europe. It will: 1) use the latest seismic reflectance data available to generate topographical maps of the whole of early Holocene Doggerland that are as accurate and complete as possible. 2) reconstruct and simulate the palaeo-environments of Doggerland using ancient DNA extracted directly from sediment cores. 3) explore the Mesolithic landscapes and also identify incipient Neolithic signals indicating early contact and development within the region of Doggerland.

Mots-clés : marine archaeology,palaeolandscapes,coastal shelf prehistoric research
Projet ERC : Lost Frontiers (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : University of Nottingham — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 0.0 €

The only lands on Earth that have not been explored in any depth by science are those that have been lost to the oceans. Global warming at the end of the last Ice Age led to the inundation of vast landscapes that had once been home to thousands of people. These lost lands hold a unique and largely unexplored record of settlement and colonisation linked to climate change over millennia. Amongst the most significant is Doggerland. Occupying much of the North Sea basin between continental Europe and Britain it would have been a heartland of human occupation and central to the process of re-settlement and colonisation of north Western Europe during the Mesolithic and the Neolithic. Within this submerged landscape lies fragmentary yet valuable evidence for the lifestyles of its inhabitants including the changes resulting from both the encroaching sea and the introduction of Neolithic technologies. This inundated landscape cannot be explored conventionally, however pioneering work by the applicant’s research group has led to the rediscovery of Doggerland through the creation of the first detailed topographic maps relating to human occupation in the Early Holocene. Within this project world-leading innovators in the fields of archaeo-geophysics, molecular biology and computer simulation will develop a ground-breaking new paradigm for the study of past environments, ecological change and the transition between hunter gathering societies and farming in north west Europe. It will: 1) use the latest seismic reflectance data available to generate topographical maps of the whole of early Holocene Doggerland that are as accurate and complete as possible. 2) reconstruct and simulate the palaeo-environments of Doggerland using ancient DNA extracted directly from sediment cores. 3) explore the Mesolithic landscapes and also identify incipient Neolithic signals indicating early contact and development within the region of Doggerland.

Mots-clés : marine archaeology,palaeolandscapes,coastal shelf prehistoric research
Projet ERC : Lost Frontiers (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : University of St Andrews — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 23118.75 €

The only lands on Earth that have not been explored in any depth by science are those that have been lost to the oceans. Global warming at the end of the last Ice Age led to the inundation of vast landscapes that had once been home to thousands of people. These lost lands hold a unique and largely unexplored record of settlement and colonisation linked to climate change over millennia. Amongst the most significant is Doggerland. Occupying much of the North Sea basin between continental Europe and Britain it would have been a heartland of human occupation and central to the process of re-settlement and colonisation of north Western Europe during the Mesolithic and the Neolithic. Within this submerged landscape lies fragmentary yet valuable evidence for the lifestyles of its inhabitants including the changes resulting from both the encroaching sea and the introduction of Neolithic technologies. This inundated landscape cannot be explored conventionally, however pioneering work by the applicant’s research group has led to the rediscovery of Doggerland through the creation of the first detailed topographic maps relating to human occupation in the Early Holocene. Within this project world-leading innovators in the fields of archaeo-geophysics, molecular biology and computer simulation will develop a ground-breaking new paradigm for the study of past environments, ecological change and the transition between hunter gathering societies and farming in north west Europe. It will: 1) use the latest seismic reflectance data available to generate topographical maps of the whole of early Holocene Doggerland that are as accurate and complete as possible. 2) reconstruct and simulate the palaeo-environments of Doggerland using ancient DNA extracted directly from sediment cores. 3) explore the Mesolithic landscapes and also identify incipient Neolithic signals indicating early contact and development within the region of Doggerland.

Mots-clés : marine archaeology,palaeolandscapes,coastal shelf prehistoric research
Projet ERC : BRuSH (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Haukeland University Hospital — Pays : Norvège — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 87210.0 €

The oral cavity is the gateway to the lower respiratory tract, and oral bacteria are likely to play a role in lung health. This may be the case for pathogens as well as commensal bacteria and the balance between species. The oral bacterial community of patients with periodontitis is dominated by gram-negative bacteria and a higher lipopolysaccharide (LPS) activity than in healthy microbiota. Furthermore, bacteria with especially potent pro-inflammatory LPS have been shown to be more common in the lungs of asthmatic than in healthy individuals. The working hypothesis of BRuSH is that microbiome communities dominated by LPS-producing bacteria which induce a particularly strong pro-inflammatory immune response in the host, will have a negative effect on respiratory health. I will test this hypothesis in two longitudinally designed population-based lung health studies. I aim to identify whether specific bacterial composition and types of LPS producing bacteria in oral and dust samples predict lung function and respiratory health over time; and if the different types of LPS-producing bacteria affect LPS in saliva saliva and dust. BRuSH will apply functional genome annotation that can assign biological significance to raw bacterial DNA sequences. With this bioinformatics tool I will cluster microbiome data into various LPS-producers: bacteria with LPS with strong inflammatory effects and others with weak- or antagonistic effects. The epidemiological studies will be supported by mice-models of asthma and cell assays of human bronchial epithelial cells, by exposing mice and bronchial cells to chemically synthesized Lipid A (the component that drive the LPS-induced immune responses) of various potency. The goal of BRuSH is to prove a causal relationship between oral microbiome and lung health, and gain knowledge that will enable us to make oral health a feasible target for intervention programs aimed at optimizing lung health and preventing respiratory disease.

Mots-clés : microbiome,genome annotation,endotoxin,immunology,asthma,lung function
Projet ERC : SLOW_SOURCE (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe sciences
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 1937932.0 €

The origins and release mechanisms of stellar winds are long-lasting open challenges in astrophysics. Stellar winds play a fundamental role in the long-term evolution of stars and the habitability of their orbiting planets. In the solar case, the wind is observed in at least two states, fast and slow winds, that differ in their bulk properties and composition, pointing to different coronal origins. A theoretical explanation for the slow wind must explain both its variable bulk properties and its peculiar composition. This includes the measured high charge states of minor ions, the abundance variation of Helium during the solar cycle and the high abundance of elements with low first ionisation potential (so called FIP effect) reaching four times the photospheric abundance. SLOW_SOURCE is a comprehensive research project that will use current and upcoming observations as well as completely novel models of the solar atmosphere to determine the origin of the slow wind. We will develop plasma transport models coupling major and all known important minor constituents along realistic coronal magnetic field lines. This model will be the first of its kind producing modelled observations (spectroscopy, imagery) and expected in situ signatures directly from the modelled minor constituents. Combined with data from space and ground-based observatories, our new multi-species, multi-temperature 3-dimensional modelling of coronal plasma will provide new ways to infer the properties of stellar winds and tools to study the fundamental transport and heating processes of stellar plasmas. Determining the enigmatic release mechanism(s) of the slow solar wind constitutes a key objective of the upcoming Parker Solar Probe mission that will obtain radically new observations right from the start of the project. The project (2019-2024) will also be an excellent preparation for the Solar Orbiter mission that should obtain its first data during the second half of the project (2022-2024).
Projet ERC : 14Constraint (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : University of California System — Pays : Etats-Unis — Rôle : Partner
Acronyme de l'entité : UC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 429875.0 €

The overall goal of 14Constraint is to enhance the availability and use of radiocarbon data as constraints for process-based understanding of the age distribution of carbon in and respired by soils and ecosystems. Carbon enters ecosystems by a single process, photosynthesis. It returns by a range of processes that depend on plant allocation and turnover, the efficiency and rate of litter decomposition and the mechanisms stabilizing C in soils. Thus the age distribution of respired CO2 and the age of C residing in plants, litter and soils are diagnostic properties of ecosystems that provide key constraints for testing carbon cycle models. Radiocarbon, especially the transit of ‘bomb’ 14C created in the 1960s, is a powerful tool for tracing C exchange on decadal to centennial timescales. 14Constraint will assemble a global database of existing radiocarbon data (WP1) and demonstrate how they can constrain and test ecosystem carbon cycle models. WP2 will fill data gaps and add new data from sites in key biomes that have ancillary data sufficient to construct belowground C and 14C budgets. These detailed investigations will focus on the role of time lags caused in necromass and fine roots, as well as the dynamics of deep soil C. Spatial extrapolation beyond the WP2 sites will require sampling along global gradients designed to explore the relative roles of mineralogy, vegetation and climate on the age of C in and respired from soil (WP3). Products of this 14Constraint will include the first publicly available global synthesis of terrestrial 14C data, and will add over 5000 new measurements. This project is urgently needed before atmospheric 14C levels decline to below 1950 levels as expected in the next decade.