Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : NLPRO (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer science and informatics
Entité participante : Open University of Israel — Pays : Israël — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 360175.7 €

Can we program computers in our native tongue? This idea, termed natural language programming, has attracted attention almost since the inception of computers themselves. From the point of view of software engineering (SE), efforts to program in natural language (NL) have relied thus far on controlled natural languages (CNL) -- small unambiguous fragments of English with strict grammars and limited expressivity. Is it possible to replace CNLs with truly natural, human language? From the point of view of natural language processing (NLP), current technology successfully extracts static information from NL texts. However, human-like NL understanding goes far beyond such extraction -- it requires dynamic interpretation processes which affect, and are affected by, the environment, update states and lead to action. So, is it possible to endow computers with this kind of dynamic NL understanding? These two questions are fundamental to SE and NLP, respectively, and addressing each requires a huge leap forward in the respective field. In this proposal I argue that the solutions to these seemingly separate challenges are actually closely intertwined, and that one community's challenge is the other community's stepping stone for a huge leap, and vice versa. Specifically, I propose to view executable programs in SE as semantic structures in NLP, and use them as the basis for broad-coverage dynamic semantic parsing. My ambitious, cross-disciplinary goal is to develop a new NL compiler based on this novel approach to NL semantics. The NL compiler will accept an NL description as input and return an executable system as output. Moreover, it will continuously improve its NL understanding capacity via online learning that will feed on verification, simulation, synthesis or user feedback. Such dynamic, ever-improving, NL compilers will have vast applications in AI, SE, robotics and cognitive computing and will fundamentally change the way humans and computers interact.

Mots-clés : natural language processing,semantic parsing,software engineering,machine learning,structure prediction
Projet ERC : EvoTrap (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : Ludwig-Maximilians-Universität München — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : LMU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2364500.0 €

Can we reconstruct in the lab the onset of molecular evolution? To trigger the autonomous emergence of the first oligonucleotide sequences, we will explore non-equilibrium boundary conditions and selective mechanisms to host the fast progressing prebiotic replication chemistry of oligonucleotides. We will explore novel water-fog microfluidic settings to boost the replication and selection of the first RNA sequences. The findings aims to enable the creation of primitive life forms in the lab, starting from simple molecules in heated rock pores of early Earth. Autonomous replication and metabolism. We will expand our thermal gradient expertise to host three replication chemistries. Using 3D printed microfluidics, we will mimick conditions in pores on early Earth. Thermophoresis will select long over short strands, accumulate small food molecules and strands will be separated by thermal convection and novel mechanisms in water-air systems. With respective collaboration partners, we will drive the replication from RNA ribozymes (Joyce), base-by-base RNA replication (Szostak) and EDC activated DNA ligation (Richert) and monitor the results with Illumina sequencing and TOF LC/MS. The ligation will be also explored with Taq ligase since we expect a cooperative replication dynamics with hypercycle-like characteristics. Thermal gradients will drive early metabolism to boost RNA polymerization and select ATP over ADP to drive modern biochemistry. Sequence selection in low pressure water-air systems. Oligonucleotides bind to water-air interfaces. and can be accumulated 800-fold by heat-driven capillary flows. Based on this, we expect interesting selection effects under microfluidic boiling, fog formation and recondensation dynamics. The settings are tested for sequence selective hydro-gelation of RNA/DNA and enhanced replication chemistry. The temperature of boiling water will be limited below 60°C by using air pressures <200mbar, mimicking very early Earth conditions.

Mots-clés : molecular evolution,minimal replication,selection,oligonucleotides,sequencing,symmetry,breaking,ligation,molecule thermophoresis,non equilibrium physics,thermal gradients,microfluidics
Projet ERC : ONCOFUM (Horizon 2020, appel 2018, Consolidator 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 : 1339814.62 €

Cancer cells undergo profound metabolic changes. However, little is known about whether and how metabolic changes drive cancer. The discovery that mutations of Tricarboxylic Acid (TCA) cycle enzymes in mitochondria predispose to cancer gives evidence that dysregulated metabolism could drive tumorigenesis. Amongst these, mutations in Fumarate Hydratase (FH) cause Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC), characterised by tumours of the skin and uterus, and renal cancer. Patients inherit one mutated copy of FH and loss of the wild-type (wt) allele occurs in tumours. Fumarate accumulation is the defining biochemical feature of these tumours. However, the mechanisms by which FH loss and fumarate accumulation lead to these tumours is unclear. In ONCOFUM, I want to elucidate the mechanisms that underpin tissue-specific tumorigenesis in HLRCC. I hypothesise that HLRCC occurs via a two-step process. Initially, loss of the wt allele in carriers of a FH mutation leads to FH deficiency. However, most of these cells die and only cells in tissues with the appropriate metabolic hardware survive. In the second step, FH loss in permissive tissues leads to phenotypic changes that lead to cancer. To assess this hypothesis, we will generate a mouse model where we inactivate FH in multiple tissues and elucidate the ensuing tissue-specific reprogramming. Then, using cellular models, we will investigate the molecular consequences of FH loss. In parallel, we will perform a comprehensive analysis of HLRCC tumours to find diagnostic and prognostic tools, and new anticancer targets, which will be validated in vitro and in vivo. The experimental framework developed in ONCOFUM will give unparalleled molecular insights into how cancer develops in different tissues in response to loss of FH and will lead to new therapeutic strategies for HLRCC, and, more generally for the many other cancers to which metabolic reprogramming contributes.

Mots-clés : mitochondria,fumarate,cancer,epigenetics,oncometabolites
Projet ERC : Secret Surface (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Radboud University Nijmegen Medical Centre — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : RUNMC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Cancer development is characterized by uncontrolled proliferation, cell survival and metabolic reprogramming. Tumour cells are surrounded by a fluid-mosaic membrane that contains tetraspanins (Tspans) which are evolutionary conserved proteins important in the formation of multiprotein complexes at the cell surface (‘tetraspanin web’). Increasing evidence indicates that Tspans are involved in cancer, still the architecture of the Tspan web in native tumour membranes and its (patho)physiological functions have not been resolved. Based on my preliminary data, I hypothesize that tumour cells contain a disrupted Tspan web in which Tspan interactions are modified leading to aberrant metabolic signalling and tumour development. This is supported by my discovery that loss of Tspan CD37 leads to spontaneous lymphomagenesis due to activation of the Akt survival pathway. The overall aim of Secret Surface is to unravel the composition, physiological functions and molecular mechanisms of the Tspan web on tumour development and clinical outcome. To achieve this, I will focus on studying lymphomas using a multidisciplinary approach: I. Detailed analyses of Tspan web composition in lymphoma to select clinically relevant Tspans (high-throughput tissue microarray technology, multispectral imaging). II. Resolve the endogenous Tspan web on lymphoma cells (super-resolution microscopy), and generation and analysis of lymphoma cells that have a complete deficiency of multiple Tspans (CRISPR/Cas9 technology). III. Decipher molecular mechanisms underlying Tspan web function in lymphoma cells (membrane organization, membrane-proximal signalling, metabolic reprogramming). With my unique toolbox of Tspan knock-outs coupled to advanced microscopy and metabolic studies, I expect that Secret Surface will lead to a new concept in cellular physiology in which cell surface organization by the Tspan web drives tumour development, which may open new horizons for the generation of new cancer therapies.

Mots-clés : lymphoma,cellular physiology,plasma membrane,signal transduction,super resolution imaging
Projet ERC : mitozippers (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : Universidad Complutense de Madrid — Pays : Espagne — Rôle : PI
Acronyme de l'entité : UCM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 149700.0 €

Cancer is one of the leading causes of death in Europe. The economic impact of cancer in Europe has been quantified with a total cost of 126 billion €, including healthcare costs and productivity losses. Although many efforts have been devoted to eradicate cancer, the current treatments are associated with severe side effects and high toxicity. Alternatively, the next generation of cancer treatments targets only malignant cells, which exhibit unique biochemical hallmarks different from their normal counterparts. For example, cancer cell mitochondria are structurally and functionally different from healthy cells. As mitochondria are the waterline of cellular viability, they represent a more effective therapeutic target as compared to current protein targeted therapies. Here, we propose a novel approach whereby the control of cell proliferation and survival is achieved by means of regulation of the membrane properties of the cancer cell mitochondria by means of a lipophilic cationic drug, which efficiently accumulates in mitochondria. Our approach meets the requirements of developing, protecting and commercializing alternative therapies leading to an improvement of life quality and survival rate of cancer patients as well as an improvement in economic terms.

Mots-clés : targeted cancer therapy,mitochodrial membranes,membrane biophysics,drug delivery
Projet ERC : CrIC (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
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 : 1500000.0 €

Cancer related inflammation (CRI) is a well-established hallmark of cancer. We recently demonstrated that the DNA damage repair SLX4 complex suppresses spontaneous and human immunodeficiency virus (HIV)-dependent pro-inflammatory cytokine production, revealing a role for this DNA repair complex in controlling innate immune responses. Bi-allelic mutations in SLX4 are involved in the onset of Fanconi Anemia (FA), a syndrome characterized, besides heightened cancer susceptibility, by severe defects of the immune system, resulting from increased pro-inflammatory cytokine levels and progressive bone marrow failure. Within this proposal, using SLX4-deficiency as a working model, I aim at investigating the molecular process underlying CRI. Based on our previous observation that the SLX4 complex binds to HIV-derived reverse-transcripts and promotes their degradation, my working hypothesis is that CRI results from the accumulation of endogenous pathological nucleic acids that are recognized by the innate immune system in the absence of SLX4. The present project should unveil the relationship between repression of pro-inflammatory cytokine production by proteins involved in DNA repair, DNA damage, and CRI, thereby opening unforeseen perspectives in the treatment of cancer patients.

Mots-clés : dna damage response,pathological nucleic acids,chronic inflammation,cancer
Projet ERC : BARB (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : Ludwig-Maximilians-Universität München — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : LMU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 500000.0 €

Cancer remains one of the main causes of death worldwide. In 2018, >50% cancer patients in Europe underwent radiotherapy. While over 80% were treated using high-energy X-rays, the number of patients receiving accelerated protons or heavy ions (charged particle therapy: CPT) is rapidly growing, with nearly 200,000 patients treated up till now. Although CPT offers a better depth-dose distribution compared to common X-ray based techniques, range uncertainty and poor image guidance still limit its application. Improving accuracy is key to broadening the applicability of CPT. In BARB, we will open a new paradigm in the clinical use of CPT by using high-intensity radioactive ion beams (RIB), produced at GSI/FAIR-phase-0 in Darmstadt, for simultaneous treatment and visualization. This will reduce range uncertainty and extend the applicability of CPT to treatment of small lesions (e.g. metastasis and heart ventricles) with unprecedented precision. The Facility for Antiprotons and Ion Research (FAIR) is currently under construction at GSI. RIB are one of the main tools for basic nuclear physics studies in the new facility. As part of the ongoing FAIR-phase-0, an intensity upgrade will increase the light ion currents in the existing SIS18 synchrotron. Within this project BARB, we will study four b+ emitters (10,11C, and 14,15O) and build an innovative hybrid detector for online positron emission tomography (PET) and g-ray imaging. This novel detector will acquire both prompt g-rays during the beam-on phase of the pulsed synchrotron beam delivery, and the delayed emission from b+ annihilation during the pulse intervals. The technique will be further validated in vivo by applying it to treatment of small tumors in a mouse model. BARB will exploit the potential of the Bragg peak in medicine. The project will tweak RIB production in nuclear physics and validate the therapeutic potential of RIB therapy in vivo by empowering simultaneous treatment and visualization.

Mots-clés : nuclear physics,medical physics,radioactive ion beams,particle therapy,radiobiology
Projet ERC : MUMOTT (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : Partner
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 97181.25 €

Capture structures without looking at them directly, but rather by probing their interaction with electromagnetic waves - this is the basic principle for the new multi-modal tensor tomography developed in this research programme. It will enable to study the arrangement of nanostructures in macroscopic samples, six orders of magnitude larger than its building blocks, allowing to apprehend the structure of complex hierarchical materials. I will use visible light observing change in their polarization state as well as the scattering of hard X-rays to probe nanostructure. Both modes capture alignment of nanostructure, while complementary in other aspects e.g. high penetration depth of synchrotron radiation and easy accessibility of laboratory polarimetric setups. At the core of MUMOTT lays the development of the methodological framework implemented in an open-source software package allowing for the reconstruction of tensors in each sub-volume or voxel of the three-dimensional tomogram. Whereas in a first step I will work out a general approach, we will incorporate flexible modules to capture details of the different types of interaction. This approach includes method development pushing the boundaries of traditional synchrotron methods to make full use of the high brilliance and coherence of the new generation of synchrotrons coming online as well as the enabling of studies with lab-based equipment. It opens up for addressing new scientific problems by widening the range of materials as well as the user community. Apart from the methodology framework we will implement the different modes to prove their capability to solve critical problems in materials and bio-science; to investigate the structure of light-weight composites based on cellulose nanofibrils, reveal how the arrangement of nanoparticles in a plasmonic composite is connected to its sensing capabilities, as well as shed light on the disruptive collagen network in liver fibrosis.

Mots-clés : small angle x ray scattering,computed tomography,soft matter
Projet ERC : SYBORG (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 1746038.0 €

Carbon dioxide (CO2) is a potent greenhouse gas whose presence in the atmosphere is a critical factor for global warming. At the same time atmospheric CO2 is a cheap and readily available carbon source that can in principle be used for the synthesis of biomass/biofuels and value-added products. However, as synthetic chemistry lacks suitable catalysts to functionalize the CO2-molecule, there is an increasing need to exploit the CO2-fixing mechanisms offered by Nature for applications at the interface of chemistry and biology. This proposal is centered on reductive carboxylation, a completely novel principle of enzymatic CO2-fixation that we discovered only recently and that is one of the most efficient CO2-fixation reactions described in biology so far. First, we will focus on understanding the novel principle of reductive carboxylation, by studying its catalysis at molecular scale and single step resolution. This will allow us to derive the first detailed catalytic framework for highly efficient CO2-fixation and enable us to engineer novel carboxylation reactions and products. Second, we will establish a new in vitro platform for the assembly and optimization of artificial ("synthetic") CO2-fixation pathways that are based on reductive carboxylation and that have been calculated to be kinetically and bioenergetically favored compared with naturally existing CO2-fixation pathways. This platform closes a long-standing gap between the theory and practice of synthetic pathway design, and will be used to develop the first functional in vitro module for CO2-fixation, a "synthetic organelle". Finally, we will realize synthetic CO2-fixation in selected biological model systems. To that end, we will implement the optimized in vitro pathways in isolated chloroplasts, as well as alpha-proteobacterial hosts to create novel CO2-fixing organelles and organisms, breaking new grounds in understanding and engineering biological systems for efficient CO2-fixation.

Mots-clés : chemical biology,co2 fixation,carboxylases,enzymes,enzymology,cell free systems
Projet ERC : HYDROMA (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
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 : 1994351.0 €

Carbonaceous chondrites (CC) are believed to be fragments of carbonaceous asteroids from the asteroidal belt. They contain up to 4wt% of organic compounds, showing a huge diversity and extremely variable H and N isotope compositions. These isotope compositions can relate to synthesis environments but the exact nature of the processes that influenced the formation of organic compounds in CC remains unresolved. Part of the issue comes from the occurrence of hydrothermal alteration on the chondrites that exhibit the largest content in organic matter. Hydrothermalism may have modified the chemical and isotopic signature of organic molecules, but the extent of these modifications is not yet constrained, leaving a lot of uncertainties on the interpretation of H and N isotope ratios. The HYDROMA project aims at determining the effects of hydrothermalism on the D/H and 15N/14N ratios of organic molecules in CC. This project will rely on an innovative experimental approach to quantify isotopic exchange of hydrogen and nitrogen between organic compounds and the hydrothermal fluid. HYDROMA will provide a self-consistent determination of the extent and kinetics of the modification of the isotopic signatures recorded in organic molecules. Hence, it will improve the understanding of H and N-isotope systematics of organic matter in CC. HYDROMA will permit using isotope composition of organic compounds to constrain the hydrothermal events (duration, temperature) on carbonaceous asteroids. This multidisciplinary research will shed new light on the origin and reprocessing of organic matter in the early solar system, and its delivery to rocky planets, including the Earth, thus disclosing the origin of prebiotic molecules on our planet.

Mots-clés : organic matter,carbonaceous chondrites,isotope fractionation,hydrothermalism,h isotopes,n isotopes,compound specific mass spectrometry,asteroids,protoplanetary disk