Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : OMPorg (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2235815.0 €

The outer membrane (OM) of Gram-negative bacteria protects against environmental insult and is central to pathogenesis hence finding ways to disrupt its integrity is a route towards new antibiotics. However, our understanding of OM biology is limited. In particular, how the OM is organised is largely unknown. My laboratory recently discovered spatiotemporal Outer Membrane Protein organisation (OMPorg) in Escherichia coli, a new organising principle that explains how OMPs are turned over. We found that OMPs cluster into islands that can be mimicked in supported bilayers using purified proteins. As cells grow, OMP islands are displaced to the poles by new islands, leading to binary partitioning of old OMPs in repository cells following septation. Another poorly understood aspect of OM biology is how protein bridges that connect the OM to the inner membrane (IM) mediate functions across the periplasm. We have discovered that the characteristic immobility of OMPs in vivo, caused by OMP clustering, becomes imposed on IM proteins (IMPs) when OMPs and IMPs become connected by protein bridges. These exciting new findings underpin OMPorg. I will focus on two species, E. coli and P. aeruginosa, and exploit the tools I have developed to ask four interrelated questions: 1. What is the molecular basis of OMP island formation? 2. Do OMPs influence IMP functionality via protein bridges? 3. Do repository cells endow bacterial populations with ‘OMP memory’? 4. Do OMP islands coordinate OM processes? I will address these questions through an interdisciplinary research programme incorporating protein chemistry and proteomics, ensemble and single molecule microscopy on live cells and in supported bilayers and molecular dynamics simulations. OMPorg will answer major outstanding questions concerning organisation in the bacterial OM and how this impacts the biology of the cell envelope, which will have ramifications for biomedicine and biotechnology.

Mots-clés : outer membrane protein,organization,bacteria
Projet ERC : MUC2GO (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : University of Gothenburg — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

The overall aim of this proposal is to explain how the mucus systems of the intestine and lung act as a first innate immune defense line to protect our mucosal surfaces. Mucins are of highly glycosylated proteins that build the mucus skeleton. We previously discovered that there are two mucus layers in the colon. The inner mucus layer built around the MUC2 mucin is attached and impenetrable to bacteria, thus separating the intestinal bacteria from the epithelial cells. However, how the dynamic colon mucus layers are formed and controlled is poorly understood. We have established an international leading position in this research area and will now address fundamental and unresolved problems of high medical importance. The capacity of the inner mucus layer to separate bacteria from the epithelium is highly dependent on the luminal bacteria. Our results suggest specific bacteria signaling via smaller molecules or bacterial fragments to the host to increase protection. We will reveal how this signaling take place, important for understanding increased western world diseases including ulcerative colitis. Of special interest is our recent finding of a single sensory goblet cell protecting the colon crypts. We have developed a fluorescent human MUC2 transgenic mouse that is instrumental for the planned studies as well as in studies of gliadin uptake from the intestine and initiator for celiac disease. We will now transfer our leading edge knowledge of intestinal mucus structure and function to the respiratory tract. Normal trachea seems to be cleared by mucus strands formed the tracheal glands, but these strands are trapped cystic fibrosis. We will also reveal how a hypothetic attached mucus layer, as described by us in colon, could explain the mucus accumulation in chronic lung diseases. The proposed project will substantially increase our basic understanding of molecular mechanisms behind several mucus related diseases and pave the way for new treatments.

Mots-clés : mucin,mucus,bacteria,colon,large intestine,small intestine,respiratory tract,lungs,copd,mass spectrometry,proteomics
Projet ERC : GloCoBank (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2408114.0 €

The overall objective of GloCoBank is to analyse the changing shape of international banking networks across the 20th century using an innovative methodology that allows greater specificity and inclusion than ever before. The bilateral correspondent banking network that will be uncovered by GloCoBank was the structure on which the global financial system was built and on which the trade and specialization that drove global development was based, but we know very little about it. When merchants settled accounts across borders, they did so through transfers from the merchant’s bank to the customer’s bank. From the time of the telegraph in the late 19th century, the contraction of time and space was accomplished by sending telegraph messages from the buyer’s home bank to an agent in the seller’s country to transfer funds to the seller’s bank. These interbank connections remain the underlying architecture of the global payments system but we do not have a complete sense of how they were built, managed or how they changed over time. Existing literature on global payments relies on official data on capital flows that are exclusively available at a national level which prevents an analysis by type of bank, sub-national region, or more specific location. Moreover, these national data on bank flows are also consistently available for most countries only from 1960, which truncates our ability to assess the changing geography of international banking during periods of upheaval such as wars, economic crisis or depression. To date there has been no comprehensive data source to accomplish this. GloCoBank will create and analyse a new set of data and combine it with extensive archival research, which will allow a much more granular assessment of the patterns and dynamics of international banking and payments. The data will capture the links between thousands of individual banks involved in international payments through bilateral correspondent banking contracts across 130 years.

Mots-clés : history of international banking,history of globalisation,international financial centres
Projet ERC : PariTorMod (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Imperial College London — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1469805.0 €

The overall theme of the proposal is the interplay between p-adic arithmetic geometry and the Langlands correspondence for number fields. At the heart of the Langlands program lies reciprocity, which connects Galois representations to automorphic forms. Recently, new developments in p-adic arithmetic geometry, such as the theory of perfectoid spaces, have had a transformative effect on the field. This proposal would establish a research group that will develop and exploit novel techniques, that will allow us to move significantly beyond the state of art. I intend to make fundamental progress on three major interlinked problems. Torsion in the cohomology of Shimura varieties: in joint work with Scholze, I proved a strong vanishing result for torsion in the cohomology of compact unitary Shimura varieties. In work in progress, we have extended this to many non-compact cases. To obtain a complete picture, I propose to develop new techniques using point-counting and the trace formula and combine them with ingredients from arithmetic geometry. Local-global compatibility is essential for establishing new instances of Langlands reciprocity. I will use the results on Shimura varieties described above to prove local-global compatibility for torsion in the cohomology of locally symmetric spaces for general linear groups over CM fields. This is one of the fundamental questions in the field. Solving it will require progress on a diverse set of problems in representation theory and integral p-adic Hodge theory. The Fontaine–Mazur conjecture is the most general reciprocity conjecture. Very little is known outside the case of two-dimensional representations of the absolute Galois group of the rational numbers, which relies crucially on a connection to p-adic local Langlands. I will attack the Fontaine–Mazur conjecture for imaginary quadratic fields. Some crucial inputs will come from the first two projects above.

Mots-clés : automorphic forms,galois representations,shimura varieties,torsion classes
Projet ERC : METAMOLE (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : University Hospital Cologne — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1550000.0 €

The overarching aim of this proposal is to identify unique features of naked mole-rat cardiac metabolism that serve as advantageous adaptations to deal with a hypoxic environment, a state relevant to heart disease. Coronary heart disease is a leading cause of death and its pathogenesis has been linked to metabolic abnormalities. The naked mole–rat has recently emerged as a rodent model of interest to biomedicine due to its extraordinarily long and healthy lifespan (>36 years). Naked mole-rats exhibit various atypical cardiac features including a remodelled metabolism that serve as adaptations to their extremely hypoxic and hypercapnic environment, and also contribute to the negligible decline in heart function with age. I will use “omics” technologies to examine the genetic, epigenetic and post-translational features underlying naked mole-rat rewired metabolism, hypoxia tolerance and myocardial fitness. I have shown that the naked mole-rat can survive extended periods under extreme hypoxia without apparent damage, by switching its metabolism to utilise fructose. Use of fructose in ischaemic conditions could therefore prove beneficial in other mammals. I will assess whether enhancing fructose metabolism via transgenic mouse models is protective under ischaemic conditions. I have shown that the transcriptional landscape of the naked mole-rat myocardium has preserved several neonatal-like features. Since neonatal mammalian heart has regenerative capacity, a quality that is quickly lost after birth, naked mole-rats may be the first adult mammalian model for heart regeneration. This project will measure regenerative capacity of the adult naked mole-rat heart and the mechanisms by which it may retain its proliferative competency. By introducing these features into the mouse I aim to validate and understand the benefit of these unique traits in promoting a healthy myocardium with possibilities for translating these discoveries into novel therapeutic strategies in man.

Mots-clés : metabolism,hypoxia,heart disease,metabolic reprogramming,regeneration,non standard organism
Projet ERC : ReNewQuantum (Horizon 2020, appel 2018, Synergy grants)
Entité participante : Aarhus University — Pays : Danemark — Rôle : Partner
Acronyme de l'entité : AU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 0.0 €

The overarching goal of ReNewQuantum is to renew the mathematical foundation behind quantum phenomena. We aim to construct a recursive and exact new approach to quantum theory. Quantum theory is one of the pillars of modern science. Its success stretches from elementary quantum mechanical models, developed a century ago by quantization of classical mechanics, to advanced quantum field theories such as the standard model of particle physics, which is the quantization of a gauge theory. However, a precise and universal mathematical formulation of the quantization procedure is still lacking. In addition, there are very few analytic methods in Quantum Mechanics and in Quantum Field Theory. They are typically based on approximation schemes which often lead to quantitative and even qualitative failures in our descriptions. In response to these shortcomings, the main objective of ReNewQuantum is to construct a completely new mathematical approach to quantization and to quantum systems. This quantum theory will provide: - a global, explicit and recursive description of the series of quantum corrections, - access to exact quantum regimes beyond perturbation theory, - a well founded mathematical theory underlying the quantization procedure, based on geometric structures, and applicable to quantum field theory and string theory. ReNewQuantum will take the lead among the world scientific community in building this new theory of quantum physics. The researchers behind ReNewQuantum have already made important contributions along these directions. The construction of a recursive and exact new approach to quantum theory with the stated properties will only be possible through their joint synergetic effort and a combination of their deep mathematical and physical expertises, including geometry, topology and the mathematical theory of quantization (Andersen, Kontsevich), and quantum mechanics, quantum field theory, random matrix theory and string theory (Eynard, Mariño).

Mots-clés : topological recursion,mirror symmetry,resurgence,deformation quantization,fukaya category,geometric recursion,quantum chern simons theory,tqft,string theory,moduli space theory
Projet ERC : STOP-HF (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University Medical Center Groningen — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UMCG
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1496875.0 €

The overarching objective of STOP-HF is to generate human induced pluripotent stem cells (hiPSC) derived cardiomyocytes from two specific forms of heart failure (HF) with a clear trigger to unravel common pathophysiological mechanisms involved in the early development of HF. The project is focused on two specific forms of HF, both with a clear trigger: pregnancy and anthracyclines. Better understanding of early molecular pathways leading to HF and knowledge about inter-individual susceptibility is needed. For detection of early changes on a molecular level cardiac tissue is needed. Generation of patient specific cardiac cells from skin fibroblasts (hiPSC technology) is a novel and innovative approach. SPECIFIC OBJECTIVES 1. Fabrication and maturation of 3D cardiac tissue from hiPS derived cardiomyocytes. 2. Generate and characterize hiPS derived cardiomyocytes and endothelial cells from females with pregnancy induced HF and unravel differences on transcriptome level. 3. Generate and characterize hiPSC derived cardiomyocytes from patients with high susceptibility and resilience to develop anthracycline-induced HF and compare them on transcriptome level. 4. Integrate the results for coding and non-coding RNAs from objective 1+2 and identify overlapping pathways. 5. Validate discoveries on transcriptome level in vitro, in vivo and apply for the development of HF in the general population. WORKPACKAGES WP1: Optimize fabrication and maturation of 3D cardiac tissue from hiPS derived cardiomyocytes WP 2A:Validate the model and compare hiPS derived cardiomyocytes and endothelial cells from PPCM and healthy sisters on transcriptome level; WP 2B:Validate the model and compare hiPS derived cardiomyocytes from both patients with high susceptibility and resilience to develop HF after anthracyclins on transcriptome level; WP 3:Integration of transcriptome data from WP 2A+2B; WP 4:Validation of novel pathways in vitro, in vivo and new onset HF in the general population.

Mots-clés : induced pluripotent stem cells,heart failure,aetiology,disease modeling,3d tissue
Projet ERC : UniPAT (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : Commissariat à l’énergie atomique et aux énergies alternatives — Pays : France — Rôle : PI
Acronyme de l'entité : CEA
Type d'entité : Recherche
Financement ERC de l'entité : 149634.0 €

The parallel transmission technology is a promising technique to counteract the radiofrequency (RF) field inhomogeneity problem in Magnetic Resonance Imaging (MRI) at ultra-high field. It consists of placing around the subject several RF transmitters that can be controlled independently in amplitude and phase. By using sophisticated algorithms, it is then possible to design the respective waveforms which lead to a uniform excitation. This powerful tool on the other hand has remained a research instrument mostly due to the calibration and calculation time necessary to exploit the technology in each exam (around 10 minutes), and the required expertise to calculate the waveforms. In this Proof-of-Concept project, we propose to establish the scientific validity, technical feasibility and market potential of universal RF pulses. The instigator of the project indeed has acquired supporting evidence during his ERC project that it is possible to generate a set of RF pulses predesigned to be robust with respect to patient variability. That way, the so-called “universal pulses” can be applied to a category of patients without any special calibration or particular expertise. The use of parallel transmission thereby could become accessible to any clinical MRI platform equipped appropriately. Universal pulses would represent a “plug and play” solution. This Proof-of-Concept project hence will be carried out by first accumulating the data necessary to create a database of RF field maps acquired on different human brains. Through the use of tools developed during the corresponding ERC project, the pulses will be designed to work robustly on the cohort. These pulses will then be blindly applied to a group of new healthy adult volunteers without any particular calibration or calculation. Experiments will be performed at 7T using a commercial RF coil to market the results better and offer a readily implementable product to companies.

Mots-clés : plug and play,parallel transmission
Projet ERC : GravityLS (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe sciences
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2863366.0 €

The past decade has witnessed a phenomenal success in relativistic cosmology. It is now possible to constrain the structure, content and evolution of the Universe with an accuracy of a few percent. The current focus of cosmology is to understand some of the fundamental problems in physics such as: the accelerated expansion of the universe, the nature of dark energy and dark matter and the initial conditions of large scale structure. Key to addressing these problems is ascertaining the role general relativity plays in cosmology. While we now have remarkable astrophysical constraints on general relativity on milliparsec scales, we have no direct cosmological constraints on gigaparsec scales. Given the quality of the up and coming cosmological data, it is now time to tackle the challenge of constraining general relativity on large scales. I propose a coordinated program to study, model and test general relativity with the aim of obtaining definitive constraints from cosmology. My programme will have three themes. A theoretical first theme will focus on developing a unified formalism for describing deviations from general relativity on cosmological scales. A phenomenological second theme will develop the tools necessary to model the three main regimes of large scale structure: horizon size (or ultra-large) scales, the quasi-static scales (which most current surveys are targeting) and the non-linear scales. In the final, observational theme I will develop the tools needed for the data analysis of current and future cosmological surveys (such as redshift and weak lensing surveys) and a complete pipeline for the analysis of the Euclid, LSST and SKA next generation surveys. As a result I will determine the state of the art constraints on general relativity on cosmological scales and in doing so, definitively establish the role of gravity in the accelerated expansion of the universe.

Mots-clés : general relativity,large scale structure
Projet ERC : UPTIME (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : University of Dundee — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 81075.71 €

The perception of the world surrounding us depends on how we illuminate and capture it. For example, our direct observation of high-speed phenomena is limited by the speed of the human visual system. A well known method to visualize fast events is to capture them at very high frame rates with high-speed cameras, and then play the movie in slow-motion, enabling us to understand what happens at short timescales. The ultimate goal of this project is to develop the fastest camera on earth, able not only to visualize the changing morphology and position of an object under investigation, but also to simultaneously capture in depth spectroscopic information in both temporal and spectral domains – all of these at unprecedented speeds, several orders of magnitude faster than the current state of the art. For the first time, this will enable the simultaneous high-speed visualization and the spatio-spectro-temporal investigation of dynamic phenomena, at timescales never before accessible. This will enable us to gain unique insights into very fast transformations such as chemical reactions, phase transitions, laser ablation and other irreversible phenomena in physics, biology and engineering. This project will achieve its ambitious objectives through the creative exploitation of novel semiconductor ultrafast lasers and photonic sampling systems, enabling the high-speed illumination and capture of events in the spatial, temporal and spectral domains. This project will pave the way for completely new insights into high-speed dynamic events, allowing us to open up entirely new perspectives into the behaviour of the world at such timescales.

Mots-clés : ultrafast photonics,high speed imaging