Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Characterization of RTEL1 mutations in Hoyeraal-Hreidarsson Syndrome (RTEL1inHHS)

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: United Kingdom
Call: Marie Skłodowska-Curie Individual Fellowships (IF-EF) (H2020-MSCA-IF-2015, 2015)
Start date: 2017-01-01
End date: 2018-12-31
Duration (months): 24.0
Total project cost (EUR): 183454.8
EU funding (EUR): 183454.8
Participants: 1
Project status: CLOSED

Hoyeraal-Hreidarsson syndrome (HHS) is a multisystem disorder with patients presenting inter-uterine growth retardation, immunodeficiency, and/or aplastic anaemia. Recently, mutations in RTEL1 have been shown to be causal for this disease. RTEL1 prevents genomic instability and maintains integrity of the telomeres by disassembling different secondary structures that arise during DNA replication, repair, and recombination.Although recent discoveries from the host lab and others have shed light on the function of RTEL1 in maintaining genome stability, many outstanding questions remain to be addressed. Currently very little is known about RTEL1 regulation or how it is dynamically recruited to replication forks and telomeres to execute its functions. Moreover, it is not known whether RTEL1 expression or recruitment is regulated by post-translational modifications. Of the 18 identified mutations, only two have been characterized. As these undefined mutations are causal for HHS and must therefore affect the RTEL1 function, their detailed characterization is likely to shed light on new aspects of its function and/or regulation. The main objective of this project is to characterize the undefined HHS mutations in RTEL1 and determine how they impair the physiological protein function, in vitro and in vivo. To this end, we will take advantage of a complementation system that permits the stable expression of RTEL1 variants in RTEL1 deficient cells, allowing us to study RTEL1 mutant contribution to RTEL1 phenotypes. We will also perform comparative proteomic analysis of the mutants to determine if they abolish specific/novel protein-protein interactions. HHS mutations that present with a defined phenotype or affect a novel interaction will be studied in vivo in a mouse model. In summary, we anticipate that the combination of approaches proposed here holds the potential to significantly contribute towards the understanding of how different mutations affect RTEL1 function.

Keywords: telomeres,genome stability,hoyeraal hreidarsson syndrome
cAMP-dependend plasticity of striatal projection neurons in health and disease (SCAMPICITY)

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-2018, 2018)
Start date: 2019-04-01
End date: 2021-03-31
Duration (months): 24.0
Total project cost (EUR): 174806.4
EU funding (EUR): 174806.4
Participants: 1
Project status: CLOSED

The project aims to reveal the so far unknown role of cAMP in structural and synaptic plasticity of striatal spiny projection neurons (SPNs) in health and disease. Striatal SPNs divide into two subgroups: the dSPNs and iSPNs. While dSPNs preferentially express the D1 dopamine (DA) receptor, iSPNs express the D2 receptor. Both are coupled to the cAMP second messenger cascade, however the D1-receptor activates and the D2-receptor inhibits it. DA has therefore opposite effects on the two SPN groups, both mediated by cAMP. Parkinson’s disease (PD) is the second most common neurodegenerative disorder. It is characterized by typical motor symptoms caused by the death of DA neurons and the subsequent lack of DA in the striatum. A long-standing but untested notion in the field is that loss of DA leads to aberrant cAMP levels and signaling in SPNs. The project will look at the role of cAMP in SPN synaptic and structural plasticity. We will use novel optogenetic tools that allow cell-type specific activation of cAMP, with high spatiotemporal resolution. Focusing on corticostriatal synaptic transmission, we want to ask if transient activation of cAMP alone is sufficient to induce plasticity (e.g. strengthening or weakening) of this synapse. Secondly, we will use known plasticity protocols and test if precise activation of cAMP can interrupted or potentiated them. Unpublished data suggest that in vivo drug treatments that presumably elevate cAMP in SPNs induce structural plasticity, i.e. loss of dendritic spines. Following this we will unravel if cell-type specific activation of cAMP is sufficient to induce structural changes and how this relates to synaptic plasticity. Lastly, we will test the long-standing notion that cAMP levels and the responsiveness of the cascade are altered in an animal model of PD. This project will advance our understanding of how SPNs work by unraveling cAMP’s role in plasticity, and potentially inform future strategies to combat PD.

Keywords: parkinson s disease,striatum,camp,plasticity
Neurobiology of sensory disturbances induced by ciguatoxins (SENSO-CIGUA)

Framework: Horizon 2020 — Excellent Science
Programme: Marie-Sklodowska-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Individual Fellowships (IF)-Global Fellowships
Action type: Marie Skłodowska-Curie actions
Panel: Life Sciences
Countries involved: France,United States
Call: Individual Fellowships (H2020-MSCA-IF-2020, 2020)
Start date: 2021-09-01
End date: 2023-08-31
Duration (months): 24.0
Total project cost (EUR): 153109.92
EU funding (EUR): 153109.92
Participants: 2
Project status: SIGNED

The IF-GF project aims to decipher in vivo the neurobiology of sensory disturbances induced by ciguatoxins (CTXs), which cause ciguatera fish poisoning and have recently become a European food safety concern as emerging toxins. CTXs are the most potent known activators of voltage-gated sodium channels, without isoform specificity. The strong predominance of specific sensory disturbances in ciguatera suggests that CTXs activate specific subsets of primary and/or dorsal horn somatosensory neurons, which is consistent with the population coding theory. The first specific objective is to characterize the molecular markers of primary and superficial dorsal horn (SDH) sensory neurons responding to CTXs and the molecular players involved in the CTX-induced spontaneous itch and cold allodynia. Next, the planned action aims to examine the role of sensitization of sensory receptors and channels in the sensations evoked, and to identify the mediators and mechanisms involved. To achieve this, the methods used will combine a behavioural test capable of distinguishing between scratching and pain behaviours, functional methods including in vivo electrophysiological recordings in SDH neurons and calcium imaging in primary neurons, and a variety of tools comprising neurotoxic ablation, genetic invalidation, and chemogenetic inhibition of specific neuronal subpopulations. These approaches, still used by a few teams around the world to explore neural circuits, are an outstanding opportunity to advance research on sensory disorders induced by CTXs. In addition, using CTXs as singular tools, the action has the potential to uniquely complement research on itch and pain neurobiology. The fellow will benefit from the world-renowned expertise and experience of the partner laboratory (at UC Davis, USA) to acquire new technical skills and knowledge essential for her future career, and from its international network to broaden her prospects for research collaboration.

Keywords: peripheral nervous system,dorsal horn,itch,neurobiology,ciguatoxin
Composite Cultural Production: Transnational and Multidisciplinary Approaches to Pre-Modern Collage (COLLAGE)

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: Social Sciences and Humanities
Countries involved: Spain
Call: Individual Fellowships (H2020-MSCA-IF-2020, 2020)
Start date: 2022-05-01
End date: 2024-04-30
Duration (months): 24.0
Total project cost (EUR): 160932.48
EU funding (EUR): 160932.48
Participants: 1
Project status: CLOSED

‘COLLAGE’ will facilitate the delivery of the 24-month project ‘Composite Cultural Production: Transnational and Multidisciplinary Approaches to Pre-Modern Collage’. The project will be undertaken under the supervision Prof. Mónica Bolufer at the University of Valencia (UVEG). The action comprises a multidisciplinary analysis of collage made in the eighteenth and nineteenth centuries, considering its multimedia manifestations, transnational spread across the British empire, and its status as a highly gendered form of cultural production. The mobility afforded by the project will facilitate the acquisition of research-specific skills through close work with Prof. Bolufer, whose highly complementary research project Circulating Gender in the Global Enlightenment: Ideas, Networks, Agencies (CIRGEN) makes UVEG an extremely apt and timely host for the project. Undertaking COLLAGE will globalise my established expertise on collage, advancing my international career as a research leader. COLLAGE has four key objectives: 1) to explore the popularity, cross-cultural movement, and diversity of composite cultural production in the eighteenth and nineteenth centuries, focusing on its manifestations in the context of the British empire; 2) to reveal the ways in which individual instances of consumption and production related to wider transnational contexts, such as trade, empire, and industry, in order to provide a better understanding of how collective values related to individual agency during this period; 3) to examine how the production of pre-modern collage expressed, reflected, and conveyed the gendered identities, emotions, and relationships of those who made, owned, and viewed it; 4) to provide an unprecedented multidisciplinary historical and theoretical framework for discussing composite cultural production that moves beyond rigid disciplinary boundaries.

Keywords: eighteenth century studies,art history
Development of an intelligent and multi-hospital end-to-end surgical process management system (OR4.0)

Framework: Horizon 2020 — Industrial Leadership
Programme: Innovation in SMEs
Action type: SME instrument
Countries involved: Spain
Call: SME instrument (H2020-SMEInst-2018-2020-2, 2018)
Start date: 2018-06-01
End date: 2020-05-31
Duration (months): 24.0
Total project cost (EUR): 1458500.0
EU funding (EUR): 1020950.0
Participants: 1
Project status: CLOSED

Healthcare expenditure represents on average 8.3% of European GDP. Hospitals are highly complex organisations, typically with thousands of employees and hundreds of admissions and operations performed every day, in large spread-out areas. They look very much like “micro-cities” and their costs represent an approximate staggering 60% of total healthcare expenditure. Daily operations in hospitals involve a range of time consuming and complicated processes (care, logistic, operative, etc.), which must run smoothly to provide (cost-) effective, safe and friendly healthcare assistance to the population. A medium-large hospital spends more than 70% of its yearly budget on surgical interventions. Healthcare cuts in recent years, sometimes reducing budgets by up to 10%, have made it more difficult to maintain the high quality and excellent performance of public health services. Indeed, waiting lists for surgical procedures are rising due to an increase in both healthcare demand and service cuts. Surprisingly, the most complex and expensive process in hospitals —the surgical process— is still managed in a rudimentary way by relying on professionals repeatedly phoning each other to look for available people (i.e. ancillary), information and essential items in time demanding situations. MYSPHERA has identified this need, which has no current solution in the market. By leveraging its cutting edge RTLS technology, MYSPHERA presents a unique and pioneering service in this project that will transform the delivery of healthcare in hospitals. Automating information, events and tasks will transform hospitals into proactive organisations. In turn, MYSPHERA will change its product portfolio to move into a higher position in the value chain. OR4.0 is an opportunity to boost one of the most prominent companies in the emerging RTLS healthcare market, which is dominated by strong US companies, and, in turn, to improve the performance of hospitals in Europe and elsewhere.

Keywords: real time location systems,processes,process mining,analytics,hospital,operation room
MatManager - New standard in road construction efficiency (MatManager)

Framework: Horizon 2020 — Industrial Leadership
Programme: Innovation in SMEs
Action type: SME instrument
Countries involved: Denmark
Call: SME instrument (H2020-SMEInst-2018-2020-2, 2019)
Start date: 2019-05-01
End date: 2020-06-30
Duration (months): 14.0
Total project cost (EUR): 1411875.0
EU funding (EUR): 988312.0
Participants: 1
Project status: CLOSED

TF-Technologies A/S, founded in 1978, is a world leader in the development and production of electronic control solutions for road construction machinery. Our 21-person team gathers +110 years of experience in the road construction and IT industries. In 2017, we generated revenues of €5.17M. Globally, it is estimated that road authorities overspend €250Bn (30% of total cost) for road construction and re-paving every year. The issue is that road building operations are prone to serious problems. Firstly, there is no way of objectively measuring road quality parameters. Secondly, if a road is found to be deficient, it must be destroyed and repaved. The MatManager system, combining hardware and software, is pioneering a completely new market for road construction efficiency. It overcomes the known issues and has already been shown to help ensure consistent road mat quality and optimize costs. It will disrupt the road construction market by providing an effective, precise and standards-driven solution. The aim of this project is to bring our Internet-of-Things enabled MatManager to market. A basic solution has been used by 50 contractors on over 134 road jobs. This provided confirmation of objective road quality measurements and documented the potential to ensure that contractors are actually meeting job tender specifications. We have advanced the solution with a patent-pending analytics and documentation platform. Now, we want to validate the advanced solution in a large-scale pilot to reach TRL 9 and full commercialization in Q1 2021, slashing spending on road projects by at least €200K/km. In order to reach these goals, we plan a budget of €1.4M for this Phase 2 project. The business opportunity is significant. Our market is €1.94Bn and will reach €3.23Bn by 2025. Through our scalable distributor-based business model, we expect a market share of 1.8%, a turnover of €50.5M, EBITDA of €24.5M and additional employment of 172 people by 2025.

Keywords: digitalization of road construction,road construction productivity,process quality management,performance management,road construction machinery,efficiency improvements,internet of things
Scattering Strings and Other Things: A Modern Approach to Quantum Gravity and the Conformal Bootstrap (QGBoot)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Starting grants
Action type: ERC actions
Panel: Fundamental constituents of matter
Panel description: Particle, nuclear, plasma, atomic, molecular, gas, and optical physics
Countries involved: France
Call: ERC Starting Grant (ERC-2019-STG, 2019)
Start date: 2020-12-01
End date: 2025-11-30
Duration (months): 60.0
Total project cost (EUR): 1444174.0
EU funding (EUR): 1444174.0
Participants: 1
Project status: SIGNED

What is the space of consistent conformal field theories (CFTs) and of theories of quantum gravity? What are the underlying physical and functional structures of AdS scattering amplitudes and large N CFT correlation functions? Can we construct string and M-theory from precision CFT computations? The conformal bootstrap program continues to generate remarkable insights into the foundational nature of quantum and conformal field theories. In the context of the AdS/CFT Correspondence, these are directly transmuted into bounds on, and properties of, the space of consistent theories of quantum gravity in anti-de Sitter spacetime (AdS). Guided by the core questions listed above and the need for new approaches to string and M-theory, I propose to develop new analytic methods within the conformal bootstrap, particularly in the context of the AdS/CFT Correspondence, with application to fundamental questions in quantum gravity including string/M-theory. The project will draw from cutting-edge techniques in CFT and in gravity, with special focus on the computation of correlation functions and their dual AdS scattering amplitudes. Specific goals include the extension and generalization of the traditional tenets of the conformal bootstrap; the explication of holographic methods for systematically computing loop-level scattering amplitudes in AdS; via AdS/CFT, a novel determination of perturbative scattering amplitudes in string and M-theory at both tree- and loop-level; and the discovery of rigorous constraints on the space of AdS vacua of string and M-theory and, by extension, on the emergence of bulk spacetime from conformal field theory microscopics.

Keywords: conformal field theory,cft correspondence,conformal bootstrap,string theory,m theory,scattering amplitudes,correlation functions,string perturbation theory
Prediction of Geospace Radiation Environment and solar wind parameters (PROGRESS)

Framework: Horizon 2020 — Industrial Leadership
Programme: Space
Action type: Research and Innovation actions
Countries involved: Ukraine,Germany,Russian Federation,Finland,Sweden,France,France,United States,United Kingdom,United Kingdom
Call: Space Weather (H2020-PROTEC-2014, 2014)
Start date: 2015-01-01
End date: 2018-07-31
Duration (months): 43.0
Total project cost (EUR): 2359235.0
EU funding (EUR): 2358230.5
Participants: 10
Project status: CLOSED

The smooth functioning of the European economy and the welfare of its citizens depends upon an ever-growing set of services and facilities that are reliant on space and ground based infrastructure. Examples include communications (radio, TV, mobile phones), navigation of aircraft and private transport via GPS, and service industries (e.g. banking). These services, however, can be adversely affected by the space weather hazards. The forecasting of space weather hazards, driven by the dynamical processes originating on the sun, is critical to the mitigation of their negative effects. This proposal brings world leading groups in the fields of space physics and systems science in order to develop an accurate and reliable forecast system for space weather. It combines their individual strengths to significantly improve the current modelling capabilities within Europe and to produce a set of forecast tools to accurately predict the occurrence and severity of space weather events. Within project PROGRESS we will develop an European tool to forecast the solar wind parameters just upstream of the Earth's magnetosphere. We will develop a comprehensive set of forecasting tools for geomagnetic indices. We will combine the most accurate data based forecast of electron fluxes at GEO with the most comprehensive physics based model of the radiation belts currently available to deliver a reliable forecast of radiation environment in the radiation belts. This project will deliver these individual forecast tools together with a unified tool that combines the forecasting tools with the prediction of the solar wind parameters at L1 to substantially increase the lead-time of space weather forecasts.

Keywords: forecast,geomagnetic indices,electron fluxes,radiation belts,solar wind
Noise and robustness in the evolution of novel protein phenotypes (NoiseRobustEvo)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Advanced grants
Action type: ERC actions
Panel: Environmental Biology, Ecology and Evolution
Panel description: Ecology, biodiversity, environmental change, evolutionary biology, behavioural ecology, microbial ecology, marine biology, ecophysiology, theoretical developments and modelling
Countries involved: Switzerland
Call: ERC Advanced Grant (ERC-2016-ADG, 2016)
Start date: 2017-10-01
End date: 2023-03-31
Duration (months): 66.0
Total project cost (EUR): 2383444.0
EU funding (EUR): 2383444.0
Participants: 1
Project status: CLOSED

Living cells are constantly barraged by perturbations that originate within themselves. Especially abundant – far more than DNA mutations – are two kinds of such perturbations. The first is gene expression noise, pervasive stochastic variation of transcript and protein levels. The second is mistranslation noise, the misincorporation of amino acids by ribosomes during protein synthesis. Organisms and protein molecules can evolve robustness – the persistence of well-adapted phenotypes – to both kinds of noise. Theory predicts that noise and robustness can affect the adaptive evolution of new proteins, but we do not know whether they help or hinder adaptive evolution. We hypothesize that noise and robustness can accelerate protein evolution both separately and jointly. To validate this hypothesis, we will evolve light-emitting fluorescent proteins towards new color phenotypes via directed laboratory evolution in E.coli. During evolution, we will manipulate expression noise by driving FP expression from noisy or quiet promoters, and we will manipulate mistranslation via host strains with low and high mistranslation rates. We will manipulate protein robustness in three biologically important ways, chaperone overexpression, gene duplication, and stabilizing selection. We will study how fast FPs evolve new colors, and analyze protein evolutionary dynamics through a combination of high-throughput sequencing, engineering of selected adaptive mutations, and data-driven modeling. Our project will show how a ubiquitous but poorly understood source of phenotypic variation affects protein innovation. It will also help engineers discover new protein functions. Moreover, our work will help establish FPs as a major platform to study protein evolutionary dynamics. By revealing noise as a new and crucial factor in protein evolution, our observations have the potential to revolutionize molecular evolution research, much like earlier studies of noise have revolutionized cell biology.

Keywords: molecular evolution,protein adaptation,epistasis,fitness landscapes,fluorescent proteins