Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : SMAPCAN (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Supramolecular attack particles (SMAPs) are proteinaceous particles ~120 nm in diameter released from cytotoxic T cell and natural killer cells. The particles have a core of cytotoxic proteins including perforin andgranzymes enveloped in a dense shell of glycoproteins including thrombospondin-1, which provides specificity for SMAP mediated killing. SMAPs released from T-cells are stable for at least 24 hours and can kill target cells autonomously. The human cell line NK92 secretes SMAPs based on inclusion of perforin and granzyme B. We have filed a patent on SMAP engineering and isolation and propose to work with experts in glioblastoma (GBM) and ovarian high-grade serous carcinoma (OC), and with interest from a biotech company with expertise in particle based therapies, to develop SMAPs as cancer therapies. GBM and OC are both diseases with high unmet need that are treated by surgical resection followed by chemo-radiation and patients succumb to local recurrence. GBM and OC don’t respond to immunotherapies. As SMAPs are autonomously cytotoxic and can readily be delivered to surgical sites to destroy residual disease after resection we see an opportunity to develop SMAPs as therapies to reduce recurrence. The next step after SYNECT completion will be to determine if SMAPs can be used to attack the tumour selectively without damage to normal tissues. We request funding to enrich SMAPs from NK92 cells supernatants and test these against GBM and OC cell lines in vitro. We will also label SMAPs with fluorescent dyes and test biodistribution and toxicity in mouse models of intravenous, intracranial and intra-peritoneal injection. This 1 year effort will enable mathematical modelling to design efficient preclinical studies in humanized mouse models in one or both of these indications that will be funded by future grants or private sector investment. These results will also enable refinement of intellectual property, value creation and commercialization plans.

Mots-clés : cancer immunotherapy,immunological synapse,cytotoxic t cells,extracellular vesicles,glioblastoma,ovarian cancer
Projet ERC : BacBio (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Universidad de Málaga — Pays : Espagne — Rôle : PI
Acronyme de l'entité : UMA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1453562.5 €

Sustainable agriculture is an ambitious concept conceived to improve productivity but minimizing side effects. Why the efficiency of a biocontrol agent is so variable? How can different therapies be efficiently exploited in a combined way to combat microbial diseases? These are questions that need investigation to convey with criteria of sustainability. What I present is an integral proposal aim to study the microbial ecology and specifically bacterial biofilms as a central axis of two differential but likely interconnected scenarios in plant health: i) the beneficial interaction of the biocontrol agent (BCA) Bacillus subtilis, and ii) the non-conventional interaction of the food-borne pathogen Bacillus cereus. I will start working with B. subtilis, and reasons are: 1) Different isolates are promising BCAs and are commercialized for such purpose, 2) There exist vast information of the genetics circuitries that govern important aspects of B. subtilis physiology as antibiotic production, cell differentiation, and biofilm formation. In parallel I propose to study the way B. cereus, a food-borne pathogenic bacterium interacts with vegetables. I am planning to set up a multidisciplinary approach that will combine genetics, biochemistry, proteomics, cell biology and molecular biology to visualize how these bacterial population interacts, communicates with plants and other microorganisms, or how all these factors trigger or inhibit the developmental program ending in biofilm formation. I am also interested on knowing if structural components of the bacterial extracellular matrix (exopolysaccharides or amyloid proteins) are important for bacterial fitness. If this were the case, I will also investigate which external factors affect their expression and assembly in functional biofilms. The insights get on these studies are committed to impulse our knowledge on microbial ecology and their biotechnological applicability to sustainable agriculture and food safety.

Mots-clés : sustainable agriculture,food safety,food borne pathogens,phytopathology
Projet ERC : MoMa-STOR (Horizon 2020, appel 2020, Synergy grants)
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : Partner
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 96484.38 €

Sustainable energy generation by water, wind, and solar has reached in the EU a mature and economic state, but further growth to tackle the climate crisis has faltered because more economic, scalable and sustainable energy storage concepts are missing. The groups of both PIs have a proven track record in this area but, interestingly they were able just recently to perform first experiments indicating big potential gains in performance. The Simon group identified a specific ion organization in nanoporous carbon electrodes leading to enhanced capacity. He also evidenced fast, new pseudocapacitive redox contribution in metal carbides of still unclear origin. The Antonietti group could not only build from oxidation stable noble carbons a 6.5 Volt supercapacitor, but also show that in those new device major storage peaks come from solvent structure changes. In another work, massive sub-potential deposition of Na-metal was observed is the Schottky transition layers of hybrid materials, thus making sodium batteries potentially save and efficient. The general aim of MoMa-STOR is to address such fundamentally new, non-classical and non-technically covered modes of energy storage and to develop the related materials base for them, to design the next generation of energy storage devices. These new modes include a) energy storage by desolvation and matrix change, b) reversible high energy bulk structure transition, and c) metal-metal and metal-semiconductor heterojunction interface effects. New modes will be carefully analysed with advanced electrochemical techniques, including quartz crystal microbalance, differential electrochemical mass spectroscopy, combined with in situ X-ray and Raman spectroscopy for instance, to gain a precise physico-chemical picture of the operation principles. In operando high resolution electron microscopy and EELS will complete the molecular understanding of the processes.

Mots-clés : electron storage,low dimensional nanomaterials,supercapacitor,ionic liquid,in operando analytics
Projet ERC : SYMPLECTIC (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
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 : 1221921.0 €

Symplectic geometry combines a broad spectrum of interrelated disciplines lying in the mainstream of modern mathematics. The past two decades have given rise to several exciting developments in this field, which introduced new mathematical tools and opened challenging new questions. Nowadays symplectic geometry reaches out to an amazingly wide range of areas, such as differential and algebraic geometry, complex analysis, dynamical systems, as well as quantum mechanics, and string theory. Moreover, symplectic geometry serves as a basis for Hamiltonian dynamics, a discipline providing efficient tools for modeling a variety of physical and technological processes, such as orbital motion of satellites (telecommunication and GPS navigation), and propagation of light in optical fibers (with significant applications to medicine). The proposed research is composed of several innovative studies in the frontier of symplectic geometry and Hamiltonian dynamics, which are of highly significant interest in both fields. These studies have strong interactions on a variety of topics that lie at the heart of contemporary symplectic geometry, such as symplectic embedding questions, the geometry of Hofer’s metric, Lagrangian intersection problems, and the theory of symplectic capacities. My research objectives are twofold. First, to solve the open research questions described below, which I consider to be pivotal in the field. Some of these questions have already been studied intensively, and progress toward solving them would be of considerable significance. Second, some of the studies in this proposal are interdisciplinary by nature, and use symplectic tools in order to address major open questions in other fields, such as the famous Mahler conjecture in convex geometry. My goal is to deepen the connections between symplectic geometry and these fields, thus creating a powerful framework that will allow the consideration of questions currently unattainable.
Projet ERC : C.NAPSE (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
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 : 214375.0 €

Synaptic scaffolding molecules control the localization and the abundance of neurotransmitter receptors at the synapse, a key parameter to shape synaptic transfer function. Most characterized synaptic scaffolds are intracellular, yet a growing number of secreted proteins appear to organize the synapse from the outside of the cell. We recently demonstrated in C. elegans that an evolutionarily conserved protein secreted by motoneurons specifies the excitatory versus inhibitory identity of the postsynaptic domains at neuromuscular synapses. We propose to use this system as a genetically tractable paradigm to perform a comprehensive characterization of this unforeseen synaptic organization. Specifically, this project will pursue 4 complementary aims: 1) Identify and characterize a comprehensive set of genes that organize and control the formation and maintenance of these scaffolds through a series of genetic screens based on the direct visualization of fluorescent acetylcholine and GABA receptors in living animals. 2) Solve the spatial synaptic organization of these scaffolds at a nanoscale resolution using super-resolutive and correlative light and electron microscopy, and analyze their dynamic behavior in vivo by implementing Single Particle Tracking imaging in living worms. 3) Decipher the role of the synaptomatrix in the organization of synaptic extracellular scaffolds and evaluate its functional contribution at the physiological and molecular levels using a candidate gene strategy and innovative imaging. 4) Analyze the formation and decline of these scaffolds at the lifetime scale and evaluate the role of synaptic activity and aging in these processes by taking advantage of the possibility to follow identified synapses over the entire life of C. elegans. Using powerful genetics in combination with cutting-edge in vivo imaging and electrophysiology, we anticipate to identify new genes and new mechanisms at work to regulate normal and pathological synaptic function.

Mots-clés : synapse,synaptic scaffold,acetylcholine receptor,gaba receptor,extracellular matrix,c  elegans,genetic screen,super resolutive microscopy,clem
Projet ERC : CONSYN (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Systems and communication engineering
Entité participante : Technical University of Darmstadt — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1996579.0 €

Synthetic biology is the bottom-up engineering of new molecular functionality inside a biological cell. Although it aims at a quantitative and compositional approach, most of today’s implementations of synthetic circuits are based on inefficient trial-and-error runs. This approach to circuit design does not scale well with circuit complexity and is against the basic paradigm of synthetic biology. This unsatisfactory state of affairs is partly due to the lack of the right computational methodology that can support the quantitative characterization of circuits and their significant context dependency, i.e., their change in behavior upon interactions with the host machinery and with other circuit elements. CONSYN will contribute computational methodology to overcome the trial-and-error approach and to ultimately turn synthetic circuit design into a rational bottom-up process that heavily relies on computational analysis before any actual biomolecular implementation is considered. In order to achieve this goal, we will work on the following agenda: (i) develop biophysical and statistical models of biomolecular contexts into which the synthetic circuit or synthetic part can be embedded in silico; (ii) devise new statistical inference methods that can deliver accurate characterization of circuits and their context dependency by making use of cutting-edge single-cell experimental data; (iii) derive new context-insensitive circuit designs through in silico sensitivity analysis and application of filtering theory; (iv) optimize protocols and measurement infrastructure using model-based experimental design yielding a better circuit and context characterization; (v) experimentally build synthetic circuits in vivo and in cell-free systems in order to validate and bring to life the above theoretical investigations. We are in the unique position to also address (v) in-house due to the experimental wetlab facilities in our group.

Mots-clés : synthetic biology,system identification,machine learning,molecular communication,feedback control,circuit design,systems biology
Projet ERC : ASSYSt (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : University Medical Center Utrecht — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Systemic Sclerosis (SSc, scleroderma) is a complex autoimmune disorder of unclear aetiology, culminating in excessive extracellular matrix deposition (fibrosis/tissue scarring) in skin and internal organs (e.g. joints, heart, lung, gastrointestinal tract and kidneys). More than half of the patients will ultimately die as a result of organ complications. The medical need is exacerbated by the lack of curative treatments and the lack of specific and sensitive molecular markers to facilitate reliable diagnosis and prognosis. My team has recently demonstrated, through research funded by the ERC Starting Grant CIRCUMVENT, that the chemokine CXCL4 is a central player in the pathogenesis of SSc. Our results suggest that CXCL4 has great potential as 1) a biomarker to assist early diagnosis, 2) a biomarker to predict SSc disease course, and 3) a therapeutic target for the treatment or prevention of fibrosis in patients with SSc. Currently, a robust, accessible, reliable, cheap and fast assay to determine CXCL4 levels for clinical use is lacking. This prohibits the use of CXCL4 to predict clinical and treatment outcome and complicates the large-scale replication experiments across multiple labs and cohorts that are necessary to validate the diagnostic value of CXCL4. Therefore, we argue that a reliable in vitro assay measuring circulating CXCL4 levels is highly needed and can be deployed as a research support tool to accelerate the implementation of clinical strategies based on CXCL4 and a clinical decision support tool in SSc to complement current diagnostic protocols. ASSYSt will focus on 1) the development of a reliable assay to adequately determine circulating CXCL4 levels irrespective of sample collection and storage conditions, 2) assessing the market potential of each of the applications listed above, and 3) defining a strong business strategy to guide route to market.

Mots-clés : systemic sclerosis,diagnostic test,commercial feasibility
Projet ERC : SENCAN (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : NKI-AVL
Type d'entité : Recherche
Financement ERC de l'entité : 2478750.0 €

Systemic treatment of advanced cancers is hampered by the development of drug resistance. To prevent resistance, my laboratory has in the past used functional genetic screens to discover several “synthetic lethal” drug combination therapies, which has resulted in 8 clinical trials to date, including one global phase 3 study. In this program, I propose a new approach to the treatment of cancer, which is not based on combinations of drugs, but rather on the sequential treatment with drugs. In a first treatment step, cells will not only be induced to stop dividing, but they will at the same time acquire a major new vulnerability that is subsequently targeted with a second drug that selectively kills cells having the newly acquired vulnerability. To accomplish this, we will take advantage of recent observations that the cellular senescence response is not only a property of primary cells, but can also be triggered in advanced cancers. Such senescent cells have dramatic changes in gene expression, chromatin structure and metabolism that we will exploit for their selective eradication. Using chemical compound libraries and loss-of-function genetic screens in cancer cells harboring a reporter gene that is activated selectively in senescent cells, we will search for genes and compounds that induce senescence in cancer cells. This will lead to the identification of compounds and/or signaling pathways whose inhibition induces senescence in cancer cells. We will also use chemical compound screens to find tools to selectively kill senescent cancer cells. We will use the targets and compounds identified in this program to test the in vivo efficacy of this “one-two punch” consecutive therapy approach: the first to induce senescence in cancer cells, the subsequent therapy to eradicate the senescent cells. We present here preliminary data that the concept of sequential drug treatment can be effective, which serves as an important proof of concept for the strategy proposed here.
Projet ERC : GAIA-BIFROST (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe sciences
Entité participante : University of Exeter — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2998750.0 €

Systems with close stellar-mass or planetary-mass companions are ubiquities in the universe. However, the processes that shape the architecture of these systems are still not understood. By 2021 the GAIA mission will provide astrometric+radial velocity orbits for millions of multiple systems. For the vast majority, GAIA will measure only photocenter displacements and not be able to resolve the individual components, preventing masses and orbital statistics to be derived. The aim of the GAIA-BIFROST project is to exploit the GAIA sample in order to identify the processes that govern the formation and dynamical evolution of binaries and planetary systems. Using VLTI+CHARA interferometry we will resolve up to ∼6000 GAIA binaries in the continuum and in spectral lines, allowing us: (a) to derive precision dynamical masses, ages, and comprehensive orbital parameter statistics that is needed to discern between different binary formation scenarios; (b) to measure the spin-orbit and spin-spin alignment for hundreds of GAIA star-star and star-planet systems. This will constrain the origin of the orbit obliquity for stars and planets, providing unique information about their formation process and dynamical history; and (c) to image companion-disk interactions in young binary systems and use them as benchmark for studying the hydrodynamical processes that determine the system architecture at formation. Furthermore, our survey will provide a legacy data set of dynamical masses and precision ages for (literally!) thousands of stars, by far exceeding all earlier work in these areas. This will impact many areas of modern astrophysics, including studies on stellar evolution and Galactic Archaeology. To unlock these powerful new observational avenues, it is important to resolve GAIA binaries close to the GAIA wavebands and at high spectral resolution. We will achieve this by commissioning the BIFROST beam combiner at VLTI, building on our recent successful instrumentation work

Mots-clés : binary formation,planet formation,star formation,binary systems,planetary systems,interferometry,vlti,chara,gaia
Projet ERC : T-NHL SUPRESSORS (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Technical University of Munich — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : TUM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2492937.5 €

T cell non-Hodgkin lymphomas (T-NHLs) are highly aggressive malignancies that are largely resistant to conventional therapies. T-NHLs remain significantly understudied, and their molecular pathogenesis is still not well defined. Comprehensive analysis of mature T-cell lymphomas has identified multiple gain-of-function mutations in T-cell receptor (TCR) signaling molecules as an overarching hallmark of T-NHL sub-entities. Under physiological conditions, these molecules control the expansion, survival and effector function of antigen sensing T cells for host defense. Presumably, the oncogenic TCR signaling variants in lymphoma enforce these TCR programs in a constitutive manner and thereby drive continuous proliferation and expansion of the malignant clone. However, experimental in vivo evidence for this hypothesis is still limited, and the negative regulatory tumor suppressor mechanisms that can counteract oncogenic T cell signaling remain largely undefined. We recently identified the inhibitory immune receptor PD-1 as a key haploinsufficient tumor suppressor in T-cell lymphoma that is inactivated in up to 30% of human cases. The overall goal of this proposal is to comprehensively model and dissect T-cell lymphomagenesis driven by oncogenically enforced T-cell receptor pathways and to identify the PD-1 dependent and independent tumor suppressor mechanisms that inhibit these events. We will additionally explore the functions of new negative regulators within the PD-1 pathway or related pathways in antigen-mediated T cell activation. We expect that our results will provide fundamental new insights into the molecular pathomechanisms of highly aggressive T cell cancers and additionally lead to the identification of new negative regulators of antigen-mediated T cell activation.

Mots-clés : t cell lymphoma