Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Pre-clinical development of a lentiviral gene therapy to treat hearing and balance loss in Usher 1B patients (MY-O-SENSES)

Framework: Horizon Europe — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Proof of concept grants
Action type: ERC actions
Countries involved: Germany
Call: ERC PROOF OF CONCEPT GRANTS2 (ERC-2022-POC2, 2022)
Start date: 2022-09-01
End date: 2024-02-29
Duration (months): 18.0
Total project cost (EUR): 150000.0
EU funding (EUR): 150000.0
Participants: 1
Project status: CLOSED

The most prevalent genetic sensory defect, sensorineural hearing loss (SNHL), affects >430 million people and results in substantial financial and social consequences. Current treatment options are limited, achieving only temporary or partial relief and are restricted to a sub-group of patients. Therefore, novel treatment options are of high clinical need. Genetic mutations play a role in the majority of SNHL cases, which makes SNHL an ideal setting for innovative clinical gene therapy approaches. Usher syndrome is an especially severe form of SNHL, with loss of vision and balance accompanying the profound deafness. The size of the underlying genes, mutations of which are causative for Usher syndrome, exceeds the cargo capacity of gene therapy vectors currently employed to treat inner ear disorders. In my ERC-funded consolidator project iHEAR, we have provided the first ground-breaking evidence of efficient gene transfer into inner ear cell types using beyond state-of-the-art lentiviral vectors (LV). As these LV have the capacity to deliver large genetic payloads, we acquired initial data demonstrating functional improvement in a knock-out mouse hearing loss model following LV application. The MY(O)SENSES PoC proposal aims to advance these valuable research results towards clinical application by completing pre-clinical development, securing IP rights and commercializing a formulated medicinal product to launch a first-in-human clinical LV gene therapy trial to treat Usher syndrome patients. This ground-breaking concept can be extended to treat late-onset hearing loss in patients with heterozygous mutations and can be transferred to similar diseases with a genetic or acquired cause. The MY(O)SENSES product will be the first and only treatment that addresses the debilitating vertigo in combination with treating hearing loss in Usher syndrome patients, having the potential to drastically improve patients' lives and benefit society.
First insight into endolysin mediated lysis in the wine microbiota (ENDOWINE)

Framework: Horizon Europe — Excellent Science
Programme: Marie Skłodowska-Curie Actions (MSCA)
Theme: Marie Skłodowska-Curie
Destination: Postdoctoral Fellowships
Action type: Marie Skłodowska-Curie actions
Panel: Environment and Geosciences
Countries involved: France
Call: MSCA Postdoctoral Fellowships 2023 (HORIZON-MSCA-2023-PF-01, 2023)
Start date: 2024-06-01
End date: 2026-05-31
Duration (months): 24.0
Total project cost (EUR): 195914.88
EU funding (EUR): 195914.88
Participants: 1
Project status: SIGNED

Grapes are the largest fruit crop worldwide and in 2023, 15.9 billion litres of wine was produced in the European Union alone. Many challenges exist in the process of converting grapes into wine, including those associated with the resident wine microbiota. This microbiota consists of several micro-organisms, including Oenococcus oeni and a variety of other lactic acid bacteria. Some members, such as O. oeni, contribute mainly positively to the final product. However, there are certain species that are responsible for organoleptic defects. Therefore, protection measures are in place to target spoiling bacteria, of which the use of sulphites is one of the most common tactics. As reduction of chemical preservatives is a relevant theme in recent years, the search for alternatives is ongoing. Microbial-based alternatives are increasingly attractive and meet the demands for chemical-free food products. One such promising alternative involves the use of endolysins, which are phage-encoded hydrolytic enzymes used by phages to degrade the peptidoglycan layer of the host bacterium at the end of their lytic replication cycle. ENDOWINE will strive to exploit phage-derived endolysins as antimicrobials in wine. With rapid activity and high specificity among the many reasons, endolysins are particularly promising. Very few experiments using endolysins in food products have been performed, but their potential has already been demonstrated in the medical and veterinary setting. Furthermore, egg white lysozyme is already applied by the wine industry. Using a multidisciplinary approach, we will first determine the diversity of endolysins in phages infecting wine LAB through in silico analysis. Candidate endolysins will be chosen, cloned, overexpressed and purified in Escherichia coli, after which their enzymatic activities and their antimicrobial spectra will be determined. Finally, their impact on wine will be examined in small and large scale fermentation experiments.

Keywords: microbiology,virology,endolysin,oenology,oenococcus oeni
Molecular exchange at the plant-fungal interface in arbuscular mycorrhiza symbiosis (SymbioticExchange)

Framework: Horizon Europe — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Consolidator grants
Action type: ERC actions
Panel: Biotechnology and Biosystems E ngineering
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: Germany
Call: ERC CONSOLIDATOR GRANTS (ERC-2022-COG, 2022)
Start date: 2024-08-01
End date: 2029-07-31
Duration (months): 60.0
Total project cost (EUR): 2000000.0
EU funding (EUR): 2000000.0
Participants: 1
Project status: SIGNED

Nutrient acquisition is the basis of life. Arbuscular mycorrhiza (AM) symbiosis of plants with nutrient-delivering fungi is detected in the oldest land plant fossils and considered a prerequisite for plant life on land. It is wide-spread in the plant kingdom and its secondary loss is the exception. AM improves plant nutrition, stress resistance and general plant performance. Breeding AM-optimized crops has significant potential for improving food security and sustainable agriculture. Understanding the molecular underpinnings of AM function is thus imperative. The hallmark of the symbiosis are the arbuscules, highly branched hyphal structures, which develop in root cortex cells. They build a large membrane interface with the plant derived peri-arbuscular membrane (PAM) that surrounds them. Most mineral nutrients are delivered from the arbuscules and taken up via the PAM into plant cells through transporter proteins. In return, the fungi receive up to 20% of the photosynthetically-fixed carbon. The balance in mineral-nutrient-gain-for-carbon-loss influences the effect of the symbiosis in plant growth and yield. However, the full range of transported nutrients, any mechanisms regulating transport and the balance in molecular exchange are unknown. ‘SymbioticExchange’ strategically integrates transcriptomics, phosphoproteomics, metabolomics and protein-protein interaction analysis, with reverse genetics, cell biology and transport physiology to identify novel plant and fungal transporters involved in symbiotic nutrient and metabolite exchange, and to understand the molecular mechanisms of their regulation. ‘SymbioticExchange’ will thus deliver major advances on the range of transporters at the plant-fungal interface, the exchanged goods and the regulation of exchange. This important knowledge-base will provide crucial clues on how nutrient exchange can be tuned for profitable agricultural application of one of the most important symbioses on earth.

Keywords: plant symbiosis,plant nutrition,beneficial fungi,nutrient transport,metabolite transport,regulation of transport
Structural and biophysical characterisation of insulin receptor and glutamate receptors AMPAR and NMDAR in complex with SorCS coreceptors 1 and 2 (SorCS)

Framework: Horizon Europe — Excellent Science
Programme: Marie Skłodowska-Curie Actions (MSCA)
Theme: Marie Skłodowska-Curie
Destination: Postdoctoral Fellowships
Action type: Marie Skłodowska-Curie actions
Panel: Chemistry
Countries involved: Denmark
Call: MSCA Postdoctoral Fellowships 2021 (HORIZON-MSCA-2021-PF-01, 2021)
Start date: 2022-05-01
End date: 2024-04-30
Duration (months): 24.0
Total project cost (EUR): 214934.4
EU funding (EUR): 214934.4
Participants: 1
Project status: CLOSED

Type II diabetes (T2D), Alzheimer’s Disease (AD) and Parkinson’s disease (PD) are common age-related diseases, which have reached endemic levels and become a burden for the global health. Lifestyle and environment are risk factors, but cannot explain all cases - genes also predispose for these diseases. Common for T2D, AD and PD is abnormal cell function associated with dysfunction of insulin receptor, AMPA receptor or NMDA receptor. The Vacuolar Protein Sorting 10 protein (VPS10P) family contain five neural type 1 transmembrane sorting receptors: sortilin, SorLA, SorCS1, SorCS2 and SorCS3, that play a central role in control of neuronal viability and function by sorting crucial proteins. SorCS1 and SorCS2 interact with and sort IR, AMPAR and NMDAR, and genetic deficiencies for SorCS1 and -2 are associated with accelerated onset of pathology, thus implicating these receptors as critical regulators for normal cell function. However, the molecular mechanisms of SorCS1 and SorCS2 mediated sorting of target receptors are not known, and with this proposal I want to determine structures and investigate interactions of SorCS1:IR, SorCS1:AMPAR and SorCS2:NMDAR complexes. Determining the structures of transmembrane SorCS1:IR, SorCS1:AMPAR and SorCS2:NMDAR complexes by cryogenic electron microscopy (cryo-EM) we will reveal molecular details about the interaction such as the role of interacting elements at cytoplasmic tails, transmembrane helices and exodomains, and how they define specificity (SorCS1 vs. SorCS2), function and regulation. The proposed project can define new positions and in translational research that aims for drug discovery for T2D, AD and PD.

Keywords: cryo em,structure,complex,vps10p family,sorcs1,sorcs2,ir,nmdar,ampar,membrane protein,structure function relationship,regulation mechanism,c terminal tail
Multisite phosphorylation in biomolecular condensates. (Condensates)

Framework: Horizon Europe — Excellent Science
Programme: Marie Skłodowska-Curie Actions (MSCA)
Theme: Marie Skłodowska-Curie
Destination: Postdoctoral Fellowships
Action type: Marie Skłodowska-Curie actions
Panel: Life Sciences
Countries involved: Denmark
Call: MSCA Postdoctoral Fellowships 2023 (HORIZON-MSCA-2023-PF-01, 2023)
Start date: 2024-04-01
End date: 2026-03-31
Duration (months): 24.0
Total project cost (EUR): 214934.4
EU funding (EUR): 214934.4
Participants: 1
Project status: SIGNED

Biomolecular condensates are membraneless organelles that serve as specialized phase-separated microenvironments within which many cellular processes can occur efficiently and with precise spatial and temporal organization. As such condensates are an important target for scientific research because they can be used as regulatory mechanisms to turn cellular processes on or off. Condensates comprise flexible multivalent biomolecules with multiple binding sites. This allows them to interact with various molecules simultaneously, enabling biomolecular clustering that can lead to phase separation. Kinase phosphorylation is a critical mechanism that triggers formation and dissolution of condensates. Once formed, condensates display emergent properties, which arise due to the collective behavior of their component biomolecules. I propose to investigate the mechanism of consecutive catalysis by kinases within condensates, and how the properties of condensates affect kinase activity. I will use synthetic condensates containing a minimal model kinase substrate that strongly partitions Protein Kinase A to examine kinase reaction kinetics in vitro and in vivo. The experiments described within will elucidate whether kinase catalysis proceeds distributively or processively within condensates. The proposed research will identify the fundamental principles of kinase-dependent condensate regulation, particularly the impact of multi-site phosphorylation on the regulatory dynamics controlling condensates. Since condenstates and kinases form a mutually responsive system regulating many basic aspects of cellular physiology, understanding how they interact will provide greater knowledge of disease mechanisms. By unraveling the intricacies of these molecular interactions, I will uncover novel insights into cellular regulation that can be used to develop innovative therapeutic strategies to address current challenges in health and disease, such as cancer and neurodegenerative disorders.

Keywords: biomolecular condensates,membraneless organelles,phase separation,intrinsically disordered proteins,kinases,enzyme kinetics,phosphorylation,signaling pathways
MATERIALS FOR SUSTAINABLE SODIUM ION CAPACITORS (HOP-ON) (MUSIC-HOP-ON)

Framework: Horizon Europe — Widening Participation and Strengthening the European Research Area
Programme: Widening participation and spreading excellence
Theme: Improved access to Excellence
Destination: Improved access to Excellence
Action type: Research and Innovation actions
Countries involved: Spain,Estonia
Call: Hop on Facility (HORIZON-WIDERA-2023-ACCESS-06, 2023)
Duration (months): 31.0
Total project cost (EUR): 434531.25
EU funding (EUR): 434531.25
Participants: 2
Project status: SIGNED

Materials for sUstainable Sodium Ion Capacitors (MUSIC) is an Horizon Europe project (HORIZON-CL4-2022-RESILIENCE-01-24, GA: 101092080) that aims to provide a solution to the need of a new supercapacitor technology that reaches energy density comparable to that of power batteries, but still recharges within few seconds and offers long cycle life with minimum efficiency loss over time. MUSIC will fabricate SIC prototype cells and will develop a 12V module prototype that incorporates an innovative management system to monitor the SoC, SoH, SoP of individual cells. The main objective of MUSIC-HOP-ON is to reinforce EU autonomy by enabling a fully European production for all the materials incorporated in MUSIC prototypes. The Estonian SME, UPC, will bring to the ongoing MUSIC consortia its knowledge and research to produce HC from wood biomass, charcoal or lignin, effectively repurposing products with low economic value. By opening high value applications to so far underused biomass that can be sourced within European industry, gaining independency from Asian suppliers. This reduces the need for imported raw materials, significantly increasing European independence in the field of batteries, and promoting a resilient and circular economy (Horizon Europe Cluster 4, Key Strategic Objective C and D). Further, UPC utilizes CO2 byproduct from biomethane factories to produce CNTs, thereby significantly reducing the CO2 footprint in MUSIC project. This innovative approach helps in the efficient utilization of industrial waste and contributes to the reduction of greenhouse gas emissions in MUSIC project. MUSIC-HOP-ON would contribute to WIDERA outcomes by involving an SME from Estonia, a country underrepresented in Horizon Europe, while UPC will gain knowledge and capabilities accessing to an ongoing MUSIC project that is working to develop a full European sustainable SIC value chain. UPC will request a budget of 386,250€, plus 10% for the coordinator management activities.

Keywords: materials engineering,sodium ion capacitors,electrical energy storage,power applications,advanced materials,transport,grid,innovative management system
Phage co-infection: a missing link in deciphering phage co-evolutionary dynamics (MULTIPHAGE)

Framework: Horizon Europe — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Starting grants
Action type: ERC actions
Panel: Environmental B iology, Ecology  and E volution
Panel description: For all organisms : Ecology, biodiversity, environmental change , evolutionary biology, behavioural ecology, microbial ecology , marine biology, ecophysiology, theoretical developments and mod elling
Countries involved: Sweden
Call: ERC STARTING GRANTS (ERC-2023-STG, 2023)
Start date: 2024-01-01
End date: 2028-12-31
Duration (months): 60.0
Total project cost (EUR): 1499401.0
EU funding (EUR): 1499401.0
Participants: 1
Project status: SIGNED

Phage genomes represent an impressive mosaicism with different genomic regions having distinct evolutionary histories resulting from horizontal gene transfer. By initiating an estimated 10^25 bacterial infections globally every second, phages encounter and recombine with DNA of the host or of prophage origin, further adding to their genome mosaicism. Accumulating evidence, including from my work, suggest that the simultaneous infection of bacterial host by multiple phages (co-infection) could also be an important driver of phage genome evolution. However, methodological limitations have so far prevented rigorous testing of this hypothesis due to failure of studying phage co-infection in natural settings. MULTIPHAGE will overcome these limitations by developing a novel approach for precisely deciphering how phage co-infection governs the co-evolutionary dynamics of phage genomes by pursuing three objectives. First, my team will quantify the prevalence of phage co-infection by constructing phage-host infection networks. Then, we will decipher the co-evolutionary relations of phage genes with no detectable sequence homology, using the novel concept of clusters of orthologous structures (COSs) and reconstructing structural phylogeny. Finally, we will unearth phage-phage interaction and co-infection strategies in high resolution by taking advantage of cultured model systems containing multiple phages co-infecting a single bacterial host population. To achieve these objectives, we will combine integrated omics methods (metaHiC proximity ligation, long-read metagenomic sequencing, and single-cell amplified genomics), COSs and structural phylogeny with high-resolution experimental confirmation of co-infection strategies. With its ground-breaking approach, MULTIPHAGE will transform our view of phage-host co-evolution by uncovering how phage co-infection and broad host range modulate the complexity of the infection network, clarifying its enigmatic co-evolutionary dynamics.

Keywords: phage evolution,phage phage interactions,phage co infection,phage genome mosaicism,phage host interactions,phage infection strategies,proximity ligation,long read metagenomics,single cell genomics,structure prediction,structure phylogeny,bioinformatics
A novel role of small RNA pathways in regulating DNA replication in polyploid cells. (sRNAUR)

Framework: Horizon Europe — Excellent Science
Programme: Marie Skłodowska-Curie Actions (MSCA)
Theme: Marie Skłodowska-Curie
Destination: Postdoctoral Fellowships
Action type: Marie Skłodowska-Curie actions
Panel: Life Sciences
Countries involved: Denmark
Call: MSCA Postdoctoral Fellowships 2023 (HORIZON-MSCA-2023-PF-01, 2023)
Start date: 2025-09-01
End date: 2027-08-31
Duration (months): 24.0
Total project cost (EUR): 230774.4
EU funding (EUR): 230774.4
Participants: 1
Project status: CLOSED

Small RNA-mediated gene regulation and DNA replication are fundamental genome-regulatory pathways essential for cellular life, organismal development, and disease prevention. While small RNA pathways are known to sequence-specifically regulate DNA copy number in some unicellular animals, such connections have yet to be found in multicellular animals. With this project, I will investigate and mechanistically characterize such a potential connection in the Drosophila animal model system. Piwi-interacting RNAs (piRNAs), a class of animal small RNAs, safeguard the germline genome against repetitive DNA proliferation by guiding repressive heterochromatin formation at target loci. In Drosophila melanogaster ovarian nurse cells, heterochromatic (peri)centromeric DNA repeats undergo selective local suppression of DNA replication thus lowering their relative copy number. Interestingly, abundant piRNAs able to target to these 'underreplicated' regions have been found, yet the potential functional interactions between small RNA genome defense and DNA replication remain unexplored. With this project, I will bridge this gap by investigating the role of satellite piRNAs in Drosophila melanogaster, focusing on the interplay between regulated DNA replication and small RNA genome defense. Two interconnected hypotheses will be examined: (1) piRNA-directed heterochromatin formation regulates centromeric DNA copy number, and (2) piRNA-regulated heterochromatin sinks alter epigenetic inheritance. To do so, I will apply advanced sequencing- and imaging-based methods for DNA copy number quantification and leverage the powerful Drosophila genetics to uncover underlying molecular mechanisms. In sum, my investigation of small RNA-based regulation of DNA replication holds the promise to reveal a new paradigm in animal genome regulation and to provide deeper insights into the mechanisms regulating genome stability and the role of piRNAs in maintaining it.

Keywords: heterochromatin,small rna,pirna,dna replication,underreplication,drosophila
Revealing Astro and Cosmo Imprints of New-Physics (RACIN)

Framework: Horizon Europe — Excellent Science
Programme: Marie Skłodowska-Curie Actions (MSCA)
Theme: Marie Skłodowska-Curie
Destination: Postdoctoral Fellowships
Action type: Marie Skłodowska-Curie actions
Panel: Physics
Countries involved: Switzerland
Call: MSCA Postdoctoral Fellowships 2024 (HORIZON-MSCA-2024-PF-01, 2024)
Start date: 2026-03-01
End date: 2028-02-29
Duration (months): 24.0
Total project cost (EUR): 307958.88
EU funding (EUR): 307958.88
Participants: 1
Project status: SIGNED

Despite decades of compelling evidence for the existence of Dark Matter (DM) from independent astrophysical and cosmological observations, the fundamental nature of 85% of the matter of the Universe is still unknown and remains one of the biggest open questions in modern physics. Progress requires advancing in two key areas: enhancing our understanding of DM properties by expanding the set of indirect gravitational probes, and seeking evidence for additional interactions between the dark and visible sectors, as predicted by well-motivated extensions of the Standard Model (SM). My proposal contributes to both objectives by developing and implementing new tools to reveal DM signals and test theories Beyond the SM with existing and upcoming telescopes. The first part of the proposal aims at detecting small-scale galactic DM substructure. It foresees the use of the upcoming ESA Gaia satellite time series observations to construct the largest catalogue of stellar accelerations ever built, conduct the most sensitive search of DM galactic subhalos with astrometric lensing effects, and measure average stellar masses from stacked start-star lensing signals. The second part focuses on designing novel searches for axion-like-particles and new radiation components interacting with photons, by relying on the spatially correlated spectral distortion features that they induce on the CMB and high-redshift quasars due to interaction with photons in the intervening late Universe structure. The expected result is to provide the most sensitive search strategies to look for these well-motivated New Physics scenarios in ongoing and upcoming survey data. My expertise in DM models, data analysis, and astro/cosmo observations, combined with the CERN Theory members' deep knowledge of DM theory and cosmological probes, and further supported by astrometry and CMB/LSS experts at local institutions, provides a strong foundation for achieving the proposed research objectives.

Keywords: astrometry,gravitational lensing,axions