Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Dissecting mGlu5 receptor internalization pathways using genetic and pharmacological tools (INTERGLU)

Framework: Horizon 2020 — Excellent Science
Programme: Marie-Sklodowska-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Individual Fellowships (IF)-Standard European Fellowships
Action type: Marie Skłodowska-Curie actions
Panel: Life Sciences
Countries involved: Denmark
Call: Individual Fellowships (H2020-MSCA-IF-2017, 2017)
Start date: 2018-11-01
End date: 2020-10-31
Duration (months): 24.0
Total project cost (EUR): 212194.8
EU funding (EUR): 212194.8
Participants: 1
Project status: CLOSED

The metabotropic glutamate receptor 5 (mGlu5) is part of the large family of G protein-coupled receptors (GPCRs) that are the target of 30-40% of marketed drugs. mGlu5 is a key regulator of synaptic plasticity in the brain and a major drug target for a wide range of diseases, such as Fragile X syndrome. Agonist-induced internalization is a major regulatory mechanism for GPCR signalling. Interestingly, mGlu5 internalizes via a mechanism that is distinct from the canonical beta-arrestin mediated pathway. However, the details of this alternative mechanism are largely unknown for mGlu5 and poorly understood for GPCRs in general. The present project has the dual aim (1) to dissect the intracellular pathways leading to mGlu5 receptor internalization and its functional implications and (2) to develop a genetic and pharmacological toolbox to study beta-arrestin independent internalization. I will generate a series of HEK293 cells where key proteins involved in a range of GPCR internalization pathways have been systematically removed by CRISPR/Cas9 genome editing. These cell lines will complement the already existing G protein alpha subunit and beta-arrestin knockout HEK293 cell lines to generate a highly efficient toolbox to study pathways and mechanisms involved in GPCR signalling, internalization and regulation. In the present project, I will employ theses cell lines to dissect pathways leading to mGlu5 internalization. To enable future studies in cells with native mGlu5 receptor expression, pharmacological tool compounds/peptides targeting key proteins identified will be developed using the genome edited HEK293 cells. This will provide essential information about the regulation of this important drug target and beta-arrestin independent internalization. Importantly, we will make the cell lines and pharmacological tool compounds available to the scientific community enabling similar studies on a much wider range of GPCRs.

Keywords: g protein coupled receptors gpcrs,metabotropic glutamate receptor 5 mglu5,crispr,cas9 genome editing,endocytosis,internalization,trafficking
Temperature InduCed K+ channel as a tool to treat neuropathic pain (TICK)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Proof of concept grants
Action type: ERC actions
Panel: Biotechnology and Biosystems Engineering
Panel description: Biotechnology using all organisms, biotechnology for environment and food applications, applied plant and animal sciences, bioengineering and synthetic biology, biomass and biofuels, biohazards
Countries involved: Italy
Call: Call for proposals for ERC Proof of Concept Grant (ERC-2020-PoC, 2020)
Start date: 2021-12-01
End date: 2023-05-31
Duration (months): 18.0
Total project cost (EUR): 150000.0
EU funding (EUR): 150000.0
Participants: 1
Project status: SIGNED

Non-invasive Control of Neuronal Activity can in principle contribute to the medical treatment of pathologic states in which the electrical activity of neurons is impaired, as in seizures and in chronic pain (CP). To this end, we are developing and validating proteins regulated by non-toxic external stimuli that freely penetrate tissues. TICK (Temperature InduCed K+ channel) is a K+ Channel reversibly regulated by Temperature in a very narrow range (37-40 °C). The open channel drives a large K+ efflux that hyperpolarizes the neuronal cell and prevents action potential firing. The effect is reversible and the channel closes when the temperature drops below 40°C. The perfect match with the temperature requirement for humans, prompts us to consider TICK as a promising medical tool for neuronal inhibition, in the treatment of CP. Chronic pain (CP) is a medical condition affecting around 20% of adults in Europe, characterised by an abnormal duration of pain (> 12 weeks). CP is extremely hard to treat, with only about half of patients reporting adequate pain relief. This situation is even worse for neuropathic pain (NP), a specific class of CP affecting 8% of global population, which leads the brain to interpret as pain normally non-painful stimuli. NP is difficult to treat and to diagnose, due to the large number of entities involved (cells, genes and proteins working in synergy). Drugs targeting the central nervous system (e.g. antidepressants and opioids) provide only partial pain relief and are nonspecific, also causing side effects like addiction and nausea, thus restraining their adoption for prolonged treatments. TICK has no side effects and also overcomes the unavoidable limit of similar optogenetic treatment previously proposed: the need of fiber optic implant to bring light. The first version of these channels, has already been tested preliminary on rats. During this project we plan to further validate the treatment and explore its commercial potential.

Keywords: neuropathic pain,ion channel,thermogenetics
Pathways, Memory and Information Processing in Matter (InfoMatter)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Advanced grants
Action type: ERC actions
Panel: Condensed matter physics
Panel description: Structure, electronic properties, fluids, nanosciences, biological physics
Countries involved: Netherlands,Netherlands
Call: ERC ADVANCED GRANT (ERC-2020-ADG, 2020)
Start date: 2021-09-01
End date: 2026-08-31
Duration (months): 60.0
Total project cost (EUR): 2499420.0
EU funding (EUR): 1249733.75
Participants: 2
Project status: SIGNED

Imagine squeezing a crumpled plastic sheet – what is its response? For complex materials – crumpled sheets, granular media, glassy materials – tiny forces already cause a nonlinear response, associated with hopping in the energy landscape, for which we lack a coherent description. The central tenet of this proposal is that this hopping allows complex materials to process information. I propose to understand and unlock the full potential of such complex materials. Central questions are: - How can we describe their nonlinear response? - What are the computational capabilities of complex matter? - Can we create materials for targeted computations? To answer these questions, I will subject macro-scale complex matter to sequentially and spatially patterned driving forces (information input), and observe the sequential response (information output). The responses to multiple forcings form an intricate web of linked pathways, which can be represented in a graph that I interpret as encoding a sequential computation. This is the central link between driving, pathways and information, which allows me to probe the algorithmic capabilities of complex materials. Recent breakthroughs in my group have brought experimental access, modelling and design of pathways within reach. In this proposal, I will investigate these pathways and will develop strategies to create algorithmic matter, using a combination of disordered – crumpling – sheets and carefully designed mechanical metamaterials; I will develop theoretical models for both. Just like a focus on the architecture of complex matter has revolutionized our view of their linear response and gave birth to mechanical metamaterials, a focus on their pathways will revolutionize our understanding of their nonlinear response and opens the door to new forms of information processing matter.

Keywords: memory and information,complex matter,mechanical metamaterials
Do liquid crystal-like phases of proteins organize membrane compartments? (LiquOrg)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Synergy grants
Action type: ERC actions
Countries involved: Spain,Spain,France,United Kingdom
Call: ERC Synergy Grant (ERC-2020-SyG, 2020)
Start date: 2021-09-01
End date: 2027-08-31
Duration (months): 72.0
Total project cost (EUR): 11237500.0
EU funding (EUR): 11237500.0
Participants: 5
Project status: SIGNED

We are in the midst of a revolution in our understanding of the internal organization of cells. In the 1950s we learned that lipid bilayer-based membranes serve as containers (organelles) within the cytoplasm. Now we are learning that liquid-like “membrane-less” organelles i.e. without any container, self-assemble based on “liquid-liquid” phase separations. We propose the seemingly radical idea that membrane-bounded organelles– like their membrane-less counterparts- are stabilized or even templated by analogous phase separations of their surface proteins into largely planar liquids akin to liquid crystals. Our unique Synergy team is organized specifically to test this “liquid crystal hypothesis” on the cell’s secretory compartments - ER exit sites (ERES) and the Golgi stack - by employing our complementary skills in physics, physical chemistry, biochemistry and cell biology. We hypothesize based on pilot experiments evidence that the ERES and Golgi self-organize as a multi-layered series of adherent liquid crystal-like phases of “golgin” and similar proteins which surround and enclose their membranes. Their differential adhesion and repulsion would specify the topology and dynamics of the membrane compartments. If this is true, it will literally rewrite the history of cell biology. We will test the ‘liquid crystal’ hypothesis directly, systematically, and quantitatively on an unprecedented scale to either modify/disprove it or place it on a firm rigorous footing. Experiments (Aim 1) with 13 pure golgins in cis and trans pairwise combinations will establish their foundational physical chemistry. Surgically engineered changes in golgins/ERES proteins will alter the rank order (hierarchy) of their affinities for each other and link phase separation physics to cell biology (Aim 2) and be used to establish the structural basis of phase separations and their specificity, and the potential for self-assembly of wholly synthetic biological organelles (Aim 3).

Keywords: 2d phase separation,protein liquid crystals,synthetic golgi,atomic force microscopy,surface forces apparatus,giant unilamellar vesicles,er exit site,golgin
Ultrasonic inspection solution for railway crossing points (SAFTInspect)

Framework: Horizon 2020 — Societal Challenges
Programme: Smart, green and integrated transport
Action type: SME instrument
Countries involved: Spain
Call: Small business innovation research for Transport and Smart Cities Mobility (H2020-SMEINST-2-2016-2017, 2017)
Start date: 2017-10-01
End date: 2020-02-29
Duration (months): 29.0
Total project cost (EUR): 1419312.5
EU funding (EUR): 993518.0
Participants: 2
Project status: CLOSED

The heart of the rail crossings points also known as “frogs”, are a mechanical installation that enable a train to switch from one track to another.Frogs are subjected to repetitive impact collisions from the rolling stock.Such actions cause fatigue cracking which compromise the structural integrity of these safety critical components.For this reason, the EU infrastructure employs manganese steel at safety critical locations such as crossing. Railway sector involves companies that need to inspect railway crossing accurately and in time.SAFTInspect is the only solution that will warranty the total inspection of the “frog” and it will also monitor the evolution through time with a Data base (Big Data). SAFTInspect is based on a Synthetic Aperture Focussing Technique (SAFT) that facilitates for the first time full volume inspection of railway crossings devices in order to detect flaws on critical parts reinforcing the railway safety regions.SAFTInspect system will improve levels of safety for the railway industry preventing train derailments.Rail operators, underground operators, rail maintenance service providers and manufacturers, will benefit from our SAFTInspect innovative device that will be used both in pre-service and in-service analysis: Pre-service: SAFT Inspect will allow the manufacturer to control every asset produced and to offer a better service to its customers (100% of quality). No special infrastructure is required, no special skills from the user. In-service:Full volumetric inspection is more effective (90%). We will reduce 85% the total time per inspection and 94% on savings from labour costs. Cracks that occur during service will be detected at an early stage in their growth cycle.Therefore, we will eliminate the unnecessary cost of replacing frogs that are not damaged (savings around €1.89M per year). From a global perspective, avoiding unscheduled maintenance, rail operators will save up to €87.5M in penalties in Europe due to train derailments.

Keywords: railway safety,frogs inspection,ultrasonic synthetic aperture foccusing technique
Sea level and extreme waves in the Last Interglacial (WARMCOASTS)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Starting grants
Action type: ERC actions
Panel: Earth system science
Panel description: Physical geography, geology, geophysics, atmospheric sciences, oceanography, climatology, cryology, ecology, global environmental change, biogeochemical cycles, natural resources management
Countries involved: Germany,Italy
Call: ERC Starting Grant (ERC-2018-STG, 2018)
Start date: 2019-04-01
End date: 2025-09-30
Duration (months): 78.0
Total project cost (EUR): 1499965.0
EU funding (EUR): 883353.75
Participants: 2
Project status: SIGNED

Past interglacials are periods of the earth’s history when climate was warmer than the pre-industrial, and are often considered as process-analogs for a future warmer climate. During the Last Interglacial (LIG, ~128-116 ka), polar temperatures were few degrees higher than pre-industrial, ice sheets were smaller and sea level was higher than today. Studies also suggest that waves in the North Atlantic might have been more intense in the LIG than today. Understanding sea level changes and extreme wave intensity during the LIG is key to assess the future of the world’s ice sheets and coastlines under warmer climatic conditions. For this reason, the LIG is the most studied among past interglacials, but recent research highlighted that the LIG is far from a ‘solved problem’, especially for which concerns sea level and coastal dynamics. There are in fact three relevant research gaps. First, widely accepted estimates suggest that LIG global mean sea level was 5-10 m higher than today, but recent studies proved that previously unrecognized processes concur to make current LIG sea level estimates very uncertain. Second, it is unclear if LIG sea level was characterized by rapid oscillations that caused sea level to rise abruptly at rates higher than at present (up to 10 mm per year in the LIG, compare with 3 mm per year today). A third research gap is related to the highly controversial notion that the LIG was characterized by ‘superstorms’, producing waves more intense than those observed today. In this project, we want to employ a multidisciplinary combination of methods to study Last Interglacial peak sea level, sea level variations and extreme waves. WARMCOASTS will develop both new datasets and merge methods from geology, earth modeling, surface processes modeling and hydrodynamic modeling to advance the current state-of-the-art. The results of this project will be functional to better understand coastal processes under slightly warmer climate conditions.

Keywords: paleo sea level changes
Twinning for the Armenian Research Infrastructure on Cancer Research (ARICE) (ARICE)

Framework: Horizon 2020 — Spreading excellence and widening participation
Programme: Widening participation and spreading excellence
Theme: Improved access to Excellence
Action type: Coordination and support actions
Countries involved: Austria,Armenia,France,Czechia
Call: Twinning (H2020-WIDESPREAD-2020-5, 2020)
Start date: 2020-09-01
End date: 2023-12-31
Duration (months): 40.0
Total project cost (EUR): 877363.75
EU funding (EUR): 877363.75
Participants: 4
Project status: SIGNED

Twinning for the Armenian Research Infrastructure on Cancer Research (ARICE) aims to increase the research infrastructure capacities in the field of cancer research in Armenia, through integrating a robust pathology background with state-of-the-art biobanking to a research-ready data structure. This will be achieved by establishing close cooperation with the leading expert-institutions in the field (Medical University Graz, Charles University and IARC) as well as by facilitating spread of the competences at institutional, national and regional level. Cancer research infrastructure has been chosen as the focus because Armenia has a very high incidence and mortality of cancers, as well as a very high prevalence (according to incidence) among rare malignant diseases, while it underperforms in cancer research when compared to the EU average. ARICE will ensure cancer research infrastructure gets appropriate attention in order to support further local research in Armenia and in the wider Caucasus region, including former Soviet Republics. New scientific developments in the field of cancer prevention, in particular in biomarker research and large population-based investigations are in place to facilitate success in research in this field. The ARICE project is going to be an important step for reaching the set goals both efficiently and effectively. The competences acquired in this field during the project realization will be easily transferable to other fields of research related to medicine, biology and medical ethics, health-economics and biostatistics. Involvement of researchers from multiple specialities (physicians of different specialities, biologists, data management specialists) hosted by the Yerevan State Medical University (YSMU) will ensure this smooth transfer of expertise.

Keywords: transfer of excellence,cancer research,clinical genetics,biobanking
Tailored IoT & BigData Sandboxes and Testbeds for Smart, Autonomous and Personalized Services in the European Finance and Insurance Services Ecosystem (INFINITECH)

Framework: Horizon 2020 — Industrial Leadership
Programme: Information and Communication Technologies
Action type: Innovation actions
Countries involved: Ireland,Germany,Spain,Spain,Ireland,Italy,Italy,Israel,Spain,Italy,Austria,Germany,Germany,Cyprus,Türkiye,Greece,Greece,Greece,Slovenia,Belgium,Greece,Greece,France,France,Netherlands,Denmark,United Kingdom,United Kingdom,Portugal,United Kingdom,United Kingdom,United Kingdom,Portugal
Call: HPC and Big Data enabled Large-scale Test-beds and Applications (H2020-ICT-2018-3, 2018)
Start date: 2019-10-01
End date: 2023-03-31
Duration (months): 42.0
Total project cost (EUR): 20745969.26
EU funding (EUR): 15870480.63
Participants: 58
Project status: SIGNED

Despite rising investments on BigData, AI and IoT in finance/insurance, financial and insurance organisations are still facing many challenges (i.e. data “silos”, regulatory complexity, lack of testbed resources) in realizing the full potential of these technologies. INFINITECH is a joint effort of global leaders in ICT and finance towards lowering the barriers for BigData/IoT/AI driven innovation, boosting regulatory compliance and stimulating additional investments. It will provide: 1)Novel BigData/IoT technologies for seamless management and querying of all types of data (e.g., OLAP/OLTP, structured/unstructured/semi-structured, data streaming & data at rest), interoperable data analytics, blockchain-based data sharing, real-time analytics, as well as libraries of advanced AI algorithms. 2)Regulatory tools incorporating various data governance capabilities (e.g. anonymization, eIDAS integration) and facilitating compliance to regulations (e.g., PSD2, 4AMLD, MIFiD II). 3)Nine novel and configurable testbeds & sandboxes, each one offering Open APIs and other resources for validating autonomous and personalized solutions, including a unique collection of data assets for finance/insurance. The project’s results will be validated in the scope of 14 high impact pilots providing complete coverage of the sectors, including Know Your Customer (KYC), customer analytics, personalized portfolio management, credit risk assessment, preventive financial crime analysis, fraud anticipation, usage based insurance, agro-insurance and more. INFINITECH will establish a market platform that will provide access to the project’s solutions, along with a Virtualized Digital Innovation Hub (VDIH) that will support innovators (FinTech/InsuranceTech) in their BigData/AI/IoT endeavors. Based on their strong footprint in the European digital finance ecosystem, the partners will engage stakeholders from all EU-28 countries, making INFINITECH synonymous to disruptive BigData/AI innovation in the target sectors.

Keywords: finance,insurance,bigdata,blockchain,interoperability,testbeds,sandboxes,regulatory compliance,htap analytics,digital innovation hub
A hybrid framework to characterize SLiM Mimicry by Leishmania (SMILE) parasites. (SMILE)

Framework: Horizon 2020 — Excellent Science
Programme: Marie-Sklodowska-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Individual Fellowships (IF)-Standard European Fellowships
Action type: Marie Skłodowska-Curie actions
Panel: Life Sciences
Countries involved: Germany
Call: Individual Fellowships (H2020-MSCA-IF-2020, 2020)
Start date: 2021-08-01
End date: 2023-07-31
Duration (months): 24.0
Total project cost (EUR): 162806.4
EU funding (EUR): 162806.4
Participants: 1
Project status: SIGNED

Pathogens invade and colonize their target host by modulating several key processes of host cells, resulting in modified physiology. Interference mechanisms are intensively studied in the case of viruses and bacteria, however, our knowledge about invasive eukaryotic pathogens is more limited. To understand how eukaryotic pathogens hijack host processes at the molecular level, Leishmania will be examined using computational methods and the results will be validated by experimental techniques. Leishmaniasis is a parasitic protozoan disease, responsible for non-resolving and chronic infection, affecting over 10 million people worldwide. Ongoing environmental changes are considered to be helping the disease to spread to new regions. Leishmania pathogenesis is poorly understood and to combat the infection and to control the disease, further insights into host-pathogen interaction are desperately needed. An integral part of the constant arms race between the host immune system and pathogens is the rapid evolution of pathogenic Short Linear Motifs (SLiMs), capable of modulating the host cell regulation. The limited sequence length of these protein-binding segments provides evolutionary advantages for the pathogen, as SLiMs can arise de novo and many can be packed into a single protein. Their properties make them hard to explore using biochemical methods alone, however, using bioinformatics approaches this process can be accelerated. SMILE aims to identify SLiMs mediating Leishmaniasis. My hierarchical strategy starts from protein level identification to detailed structural characterisation of host-pathogen interactions, as an ultimate goal. The description of SLiMs already suggests novel therapeutic strategies to counteract mutation-based diseases. The outcome of the project has the potential to suggest targets for the development of similar treatments against eukaryotic parasitic diseases.

Keywords: protein protein interactions,short linear motifs,leishmania,intracellular eukaryotic parasites,neglected tropical diseases