Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : TENDO (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : University of Geneva — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UNIGE
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2257546.0 €

The target of the bacterial macrolide rapamycin, TOR, is a ser/thr protein kinase that assembles into two distinct protein complexes, conserved from yeast to human, we named TORC1 and TORC2. TORC1 is directly bound and inhibited by rapamycin and studies with rapamycin have revealed that TORC1 plays a central role in coupling nutrient cues to biomass synthesis and turnover. The lack of a specific inhibitor for TORC2 has made the study of this complex much more challenging. We overcame this challenge by solving the structure of yeast TORC2 which revealed why it is insensitive to rapamycin and enabled us to create a rapamycin-sensitive TORC2 variant. We also developed two small molecules, one that dissipates plasma membrane (PM) tension and the other that serves as a biosensor of PM tension. With this suite of chemical-biology tools we confirmed that TORC2 functions in a mechanotransduction pathway to maintain tension homeostasis of the PM. Concurrently, solving the structure of TORC1 revealed that its activity is regulated via assembly into a huge, inactive helix which we named a TOROID – TORC1 Organized in an Inactive Domain. In this grant, was ask if these major advances are transferable; i.e. can lessons learned regarding TORC2 be applied to TORC1, and vice versa? Our major aim is to determine if and how TORC1 regulates vacuolar membrane (VM) tension. To this end, we will develop novel chemical probes to monitor VM tension and we will use genetic screens, quantitative phosphoproteomics, in vitro assays, high-throughput compound screens, STORM and FRAP imaging, and state-of-the-art cryo-EM to learn how TORC1 senses and regulates VM tension. Our other aim, prompted by our TOROID discovery, is to solve the TOROID-like structure that TORC2 forms upon glucose depletion. This work will reveal new mechanisms in growth control, and details in TORC1 and TORC2 regulation that may inform future therapeutic interventions for these medically relevant signalling complexes.

Mots-clés : target of rapamycin  tor  signaling
Projet ERC : TERMITES (Horizon 2020, appel 2016, 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 : 150000.0 €

The technology of femtosecond lasers now makes it possible to reach enormous light intensities with only moderate amounts of energy. These so-called Ultra-High Intensity (UHI) lasers have led to the development of a very active research field, which studies the interaction of light with matter at these extreme intensities. This field is largely motivated by the prospects of generating compact sources of high-energy particles and short-wavelength light, which are being foreseen for applications in particle physics, material science, nuclear fusion technology, medicine. The actual feasibility of the promising applications of UHI lasers will largely depend on the availability of more reliable and controlled laser systems. In this context, the recent results obtained in the framework of the ERC project PLASMOPT have shown that both major obstacles and great prospects towards this goal are related to space-time couplings (STC) – i.e. a spatial dependence of the laser pulse temporal structure. Yet, there is still no device capable of measuring these STC. The goal of the present project is thus to bring up on the market the first STC measurement device, called TERMITES. This will allow identifying the source of the residual STC, and then eliminating them to reach optimal performances, thus reducing the cost needed to reach a given laser peak intensity by hundreds of k€ or more. It will also have indirect societal benefits, by contributing to the maturation of the technology of UHI lasers, and thus favouring their foreseen societal and industrial applications. Two key tasks of this project are 1- building two to three industrial demonstrators of TERMITES and 2- using these demonstrators to perform a test and validation campaign on a representative set of fs lasers. Depending on the findings of this campaign, this device will be commercialized either through a technology transfer through licensing to an existing company, or through a start-up creation.

Mots-clés : optics,ultrafast optics,metrology,ultraintense lasers,femtosecond lasers,interferometry,fourier spectroscopy
Projet ERC : SMART (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Tel Aviv University — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1937500.0 €

The terahertz optical regime, covering the long wavelength end of the optical spectrum, has been for many years the least explored spectral regime. Recent interest in this regime has led to important emerging applications spanning many disciplines including medical, biological, materials sciences, communications, security, and basic sciences. However, advances in these emerging applications are held back by the lack of good and controllable terahertz light sources. I propose to lead a potential breakthrough in this field by developing a new family of THz sources with unmatched functionality. The developed sources will be based on nano-engineered nonlinear heterostructured metamaterials, man-made materials with artificial optical properties. The proposal is based on very recent studies that show that metamaterials can be used to emit THz light with excellent efficiency, comparable to the best available nonlinear materials in nature. In addition it relies on our recent experimental demonstrations of functional nonlinear metamaterials that allow unprecedented control of nonlinear optical interactions. We will apply this recent knowledge to design novel active metamaterials that efficiently emit THz light at any desired frequency, shape and polarization, focus it directly from the emitter to a desired sample location and even actively steer and modify its radiation properties all-optically. In addition, we will enhance the THz generation efficiency from metamaterials by more than three orders of magnitude compared to the state of the art. We will also use our expertise to fabricate large scale and multi-layered THz light emitting metamaterials by leveraging novel nanolithography methods. Overall I expect that the outcome of this research will be in development of one of a kind family of THz light emitters that will lead to the, long sought for, leap in THz technology and will open the door to new applications and to new tools for advancing fundamental science.

Mots-clés : nonlinear optics,metamaterials,plasmonics,beam shaping
Projet ERC : SPECTRUM (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : Tel Aviv University — Pays : Israël — Rôle : Partner
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 166896.25 €

The theme of this proposal is the study of random operators associated with some geometric structure, and the influence of the geometry on the spectral properties of the operator. Such operators appear in problems from theoretical physics, and lead to new and interesting mathematical structures. One circle of questions is related to random operators, which describe the motion of a quantum particle in a disordered medium, such as random band matrices. The behaviour of the particle is influenced by the underlying geometry, as quantified by the (non-rigorous) Thouless criterion for localisation in terms of the mixing time of the classical random walk; in the context of random band matrices, the predictions of the Thouless criterion are supported by additional (non-rigorous) arguments. These predictions have so far not been rigorously justified; an exception is my own result, validating it at the spectral edges. One of our goals is to develop new methods, which would be applicable in the bulk of the spectrum, for random band matrices and other operators with geometric structure. Another circle of questions is given by random processes taking values in large random matrices. The spectral properties of the random matrix at every point of the underlying space are described by the random matrix theory; but how does the spectrum evolve along the underlying space? The richness of this question is apparent from the one-dimensional case of Dyson Brownian motion. We intend to study the local eigenvalue statistics of general matrix-valued random processes with multi-dimensional underlying space; to give a complete description of the random processes which appear in the limit, first for the spectral edges and then for the bulk of the spectrum, and to explore the appearance of these processes in a variety of basic questions of mathematical physics.

Mots-clés : random operators,spectral theory,random matrices
Projet ERC : EVEREST (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : Partner
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 0.0 €

The therapeutic benefits of mesenchymal stem cells (MSCs), the state-of-the-art treatment for healing bone defects following trauma, resection of cancerous bone tumors, or metabolic bone diseases, has been attributed to their secreted factors. The regenerative potential of MSC-secreted extracellular vesicles (EVs), nanoparticles which deliver bioactive cargo (nucleic acids, proteins, and lipids) between cells, has recently been reported. The applicant will embark upon frontier research with the objective of progressing beyond the state-of-the-art, by harnessing the therapeutic effects of MSCs, but in a cutting-edge, cell-free manner, by developing high potency EV-based bone replacements. This objective will be addressed by firstly testing novel hypotheses to delineate how culture environments, specifically mechanical cues (substrate elasticity and 3D dynamic), hypoxia, and cell stress can modulate the cargo of EVs secreted by MSC. Size exclusion chromatography, which separates EVs from soluble proteins will be employed. Heterogeneity of EV cargo and functionality between human MSC donors will also be evaluated. Answering these hypotheses will permit the intelligent design of targeted EV therapies. The hypothesis that EV-functionalized constructs, fabricated by 3D-printing, will lead to controlled and sustained release of EVs and induce bone formation in vivo will best tested. Together, this will answer critical questions, namely the most favorable environment for collection of potent EVs for regenerative medicine, which secretome component (EV, soluble factors) is responsible for bone regeneration, and whether MSC cell therapy can be replaced by cell-free EVs. EVEREST will develop a platform for targeted EV delivery in ground-breaking, easy to transport and handle, ‘off-the-shelf’ anatomically correct constructs, which have the potential to reduce pain by elimination of bone or bone marrow harvest, and revolutionize the treatment of bone defects.

Mots-clés : regenerative medicine,bone regeneration,extracellular vesicles,tissue engineering,bioengineering,3d printing
Projet ERC : CHROMATADS (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : University of Hohenheim — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 779168.92 €

The three-dimensional organization of the genome, which strikingly correlates with gene activity, is critical for many cellular processes. The evolution of molecular techniques has allowed us to unveil chromatin structure at an unprecedented resolution. The most intriguing chromatin structures observed in animals are TADs (Topologically Associating Domains), which represent the functional and structural chromatin domains demarcating the genome. Structural proteins such as insulators proteins, on the other hand, have been shown to play crucial roles in mediating the formation of TADs. However, major structural factors relevant to chromatin structure are still waiting to be discovered in land plants. My preliminary work shows that TADs are widely distributed across the rice genome, and motif sequence analysis suggests the enrichment of plant-specific transcription factors at TAD boundaries, which jointly give rise to an exciting hypothesis that these proteins might be the long-sought-after insulators in land plants. By using various state-of-the-art molecular and computational tools, this timely project aims to fill a huge gap in plant functional genomics and substantially advance our understanding of three-dimensional chromatin structure. This project consists four major aims, which collectively will uncover the identities of plant insulator proteins and generate insights into the dynamics of structural chromatin domains during stress adaptation. Aim 1 will identify and characterize the stability and plasticity of functional chromatin domains in the rice genome during temperature stress adaptation. Aim 2 will identify insulator elements and other structural features of chromatin packing in the Marchantia polymorpha genome from a structural genomics approach. Aim 3 will establish the role of candidate proteins as plant insulators. Lastly, Aim 4 will generate functional insights into the molecular mechanism by which plant insulators shape the three-dimensional genome.

Mots-clés : chromatin,hi c,insulator protein
Projet ERC : TOPMAT (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 2070000.0 €

The topologies of the electronic and magnetic structure in reciprocal and real space underlies much of condensed matter physics. Moreover, the properties of single crystals with particular topological electronic structures can mimic phenomena found in high energy physics and cosmology. New classes of quantum materials are found in insulators and semimetals that exhibit non-trivial topologies: they display a plethora of novel phenomena including: topological surface states; new Fermions such as Weyl, Dirac or Majorana; and non-collinear spin textures such as Skyrmions. A hallmark of many of these new quantum properties that are derived from fundamental symmetries of the bulk, is that they are topologically protected. Just recently a general scheme to identify novel Fermions was proposed that is based on the symmetries and the Wyckhoff positions of relevant space groups. These new types of Fermions are a groundbreaking concept beyond the known Dirac and Weyl and have no high-energy counterparts. The translation of these theoretical concepts into realizable materials is one focus of this proposal. The next step is to apply this approach to magnetic space groups so as to identify new magnetic Fermions. We will engineer these topological materials via synthesising high quality single crystals and by applying for example high magnetic fields and high pressure, to tune topological phase transitions, electrical transport properties and surface states. Particularly high-pressure Hall measurements will be developed. Hall measurements allow the investigation of the fundamental electrical transport properties of topological materials such as their carrier densities, oscillation frequencies, mobilities, and anomalous and topological Hall effects. The PI and her team have already synthesized more than 50 different topological materials as single crystals. To boost topological science in Europe even further a single crystal platform will be established within the proposed project.

Mots-clés : topological materials,hall effect,single crystals
Projet ERC : CutLoops (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : Trinity College Dublin — Pays : Irlande — Rôle : PI
Acronyme de l'entité : TCD
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1954065.02 €

The traditional formulation of relativistic quantum theory is ill-equipped to handle the range of difficult computations needed to describe particle collisions at the Large Hadron Collider (LHC) within a suitable time frame. Yet, recent work shows that probability amplitudes in quantum gauge field theories, such as those describing the Standard Model and its extensions, take surprisingly simple forms. The simplicity indicates deep structure in gauge theory that has already led to dramatic computational improvements, but remains to be fully understood. For precision calculations and investigations of the deep structure of gauge theory, a comprehensive method for computing multi-loop amplitudes systematically and efficiently must be found. The goal of this proposal is to construct a new and complete approach to computing amplitudes from a detailed understanding of their singularities, based on prior successes of so-called on-shell methods combined with the latest developments in the mathematics of Feynman integrals. Scattering processes relevant to the LHC and to formal investigations of quantum field theory will be computed within the new framework.

Mots-clés : scattering amplitudes,feynman integrals,perturbative quantum field theory,gauge theory,supersymmetric gauge theory,quantum chromodynamics  qcd,nlo computations,nnlo computations
Projet ERC : RETVOLUTION (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Barcelona Supercomputing Center — Pays : Espagne — Rôle : PI
Acronyme de l'entité : BSC
Type d'entité : Recherche
Financement ERC de l'entité : 844508.31 €

The traditional view is that species and their genomes evolve only by vertical descent, leading to evolutionary histories that can be represented by bifurcating lineages. However, modern evolutionary thinking recognizes processes of reticulate evolution, such as horizontal gene transfer or hybridization, which involve total or partial merging of genetic material from two diverged species. Today it is widely recognized that such events are rampant in prokaryotes, but a relevant role in eukaryotes has only recently been acknowledged. Unprecedented genomic and phylogenetic information, and recent work from others and us have shown that reticulate evolution in eukaryotes is more common and have more complex outcomes than previously thought. However, we still have a very limited understanding of what are the impacts at the genomic and evolutionary levels. To address this, I propose to combine innovative computational and experimental approaches. The first goal is to infer patterns of reticulate evolution across the eukaryotic tree, and relate this to current biological knowledge. The second goal is to trace the genomic aftermath of inter-species hybridization at the i) long-term, by analysing available genomes in selected eukaryotic taxa, ii) mid-term, by sequencing lineages of natural fungal hybrids, and iii) short-term, by using re-sequencing and experimental evolution in yeast. A particular focus is placed on elucidating the role of hybridization in the origin of whole genome duplications, and in facilitating the spread of horizontally transferred genes. Finally results from this and other projects will be integrated into emerging theoretical frameworks. Outcomes of this project will profoundly improve our understanding of reticular processes as drivers of eukaryotic genome evolution, and will impact other key aspects of evolutionary theory, ranging from the concept of orthology to the eukaryotic tree of life.

Mots-clés : hybridization,horizontal gene transfer,genome evolution,eukaryotes,fungi
Projet ERC : RETVOLUTION (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Institute for Research in Biomedicine — Pays : Espagne — Rôle : Partner
Acronyme de l'entité : IRB;IRB-CERCA
Type d'entité : Recherche
Financement ERC de l'entité : 880135.56 €

The traditional view is that species and their genomes evolve only by vertical descent, leading to evolutionary histories that can be represented by bifurcating lineages. However, modern evolutionary thinking recognizes processes of reticulate evolution, such as horizontal gene transfer or hybridization, which involve total or partial merging of genetic material from two diverged species. Today it is widely recognized that such events are rampant in prokaryotes, but a relevant role in eukaryotes has only recently been acknowledged. Unprecedented genomic and phylogenetic information, and recent work from others and us have shown that reticulate evolution in eukaryotes is more common and have more complex outcomes than previously thought. However, we still have a very limited understanding of what are the impacts at the genomic and evolutionary levels. To address this, I propose to combine innovative computational and experimental approaches. The first goal is to infer patterns of reticulate evolution across the eukaryotic tree, and relate this to current biological knowledge. The second goal is to trace the genomic aftermath of inter-species hybridization at the i) long-term, by analysing available genomes in selected eukaryotic taxa, ii) mid-term, by sequencing lineages of natural fungal hybrids, and iii) short-term, by using re-sequencing and experimental evolution in yeast. A particular focus is placed on elucidating the role of hybridization in the origin of whole genome duplications, and in facilitating the spread of horizontally transferred genes. Finally results from this and other projects will be integrated into emerging theoretical frameworks. Outcomes of this project will profoundly improve our understanding of reticular processes as drivers of eukaryotic genome evolution, and will impact other key aspects of evolutionary theory, ranging from the concept of orthology to the eukaryotic tree of life.

Mots-clés : hybridization,horizontal gene transfer,genome evolution,eukaryotes,fungi