Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
A multilevel approach to address the role of Archaeal Symbionts in the Evolution of Life (ASymbEL)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Starting 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: Netherlands
Call: ERC STARTING GRANTS (ERC-2020-STG, 2020)
Start date: 2021-02-01
End date: 2026-01-31
Duration (months): 60.0
Total project cost (EUR): 1869946.0
EU funding (EUR): 1869946.0
Participants: 1
Project status: SIGNED

Microbial symbioses play an essential role in most aspects of life’s evolution and enabled major evolutionary events such as the origin of eukaryotes. But in spite of the importance of symbioses, our knowledge is based on a limited number of microbial host-symbiont systems, few of which include Archaea. Notably, recent cultivation-independent approaches have revealed two hugely diverse microbial groups of putative deep-branching archaeal and bacterial symbionts referred to as DPANN and CPR, respectively. The major aims of ASymbEL are to test the hypotheses that (a) DPANN, together with CPR, have key positions in the tree of life, requiring to revise our view on the early evolution of cells and (b) that the diverse DPANN substantially shape the evolution of life through symbiont-host interactions. This will be achieved using a unique three-pronged strategy that will integrate knowledge from both micro- and macroevolutionary levels: I will place the diverse DPANN in a rooted tree of life including CPR, reconcile the history of their genome content evolution and identify novel host-symbiont systems using sophisticated phylogenomic approaches combined with microscopy. Further, I will elucidate fundamental principles of their genome evolution and interactions, for the first time using experimental evolution approaches to study two cultivated DPANN symbionts in co-culture with their hosts. Finally, I will determine the dynamics of natural populations of known and newly identified archaeal host-symbiont systems and the influence of symbionts on host population structure and genome evolution using a unique approach combining single-cell, metagenomics and population genomics. Altogether, this will allow to provide key insights into the global impact of these symbionts in the deep origins and diversification of cellular life on Earth. Thereby, ASymbEL paves the way for a deeper understanding of symbiotic evolutionary theory and the fundamental laws of cellular evolution.

Keywords: tree of life,archaea,dpann radiation,macro and microevolution of symbiosis,deep microbial roots,complementary genomics and experimental approaches
Bone healing mechanomics in a mouse model of accelerated aging. (MechanoHealing)

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: Switzerland
Call: Individual Fellowships (H2020-MSCA-IF-2020, 2020)
Start date: 2022-09-01
End date: 2024-08-31
Duration (months): 24.0
Total project cost (EUR): 191149.44
EU funding (EUR): 191149.44
Participants: 1
Project status: SIGNED

Delayed bone healing or failed non-unions account for 5 – 10% of all bone fractures and present a challenging problem in regenerative medicine. Bone healing is a mechano-sensitive process; thus, mechanical stimuli can either enhance or impair fracture healing. The molecular mechanisms underlying this phenomenon are complex and poorly understood. Consequently, clinical applications which harness this mechano-sensitivity to enhance healing are limited. It has also contributed to a lack of consensus on whether bone exhibits age-associated declines in mechano-sensitivity. With this in mind, I present a multi-scale, multi-disciplinary approach to develop a molecular-based understanding of bone healing mechanobiology and to investigate how this mechano-sensitivity is compromised with age. Using an established femur defect model in young and aged mice, my proposed approach will apply state-of-the-art techniques to spatially map: (i) the local mechanical environment, (ii) the molecular profiles of single cells, and (iii) the local tissue nanostructure within the fracture callus. By combining single-cell “omics” technologies with established tissue-scale models of bone mechanobiology, MechanoHealing will quantify how mechanical stimuli are translated by individual cells and subcellular components to form bone. MechanoHealing will also permit investigations into potential pathways by which mechanical stimuli influence formation of the nanostructure of bone – a key determinant of the overall fracture resistance of bone. Identification of the molecular mechanisms of mechanically-driven bone formation will lead to new strategies and novel therapeutic targets to promote better and faster repair. Specifically, it will drive the development of safe, targeted and individualized mechanical intervention therapies. Furthermore, insights into age-associated declines in mechano-sensitivity will better equip surgeons to optimize outcomes in compromised healing environments.

Keywords: bone healing,bone repair,aging,mechanobiology,mechanotransduction,mouse models
Integrated drug discovery approach to generate brain-penetrant inhibitors of glioblastoma cell proliferation (BRAINHIB)

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: Individual Fellowships (H2020-MSCA-IF-2016, 2016)
Start date: 2018-03-01
End date: 2020-02-29
Duration (months): 24.0
Total project cost (EUR): 183454.8
EU funding (EUR): 183454.8
Participants: 1
Project status: CLOSED

Glioblastoma multiforme (GBM) is the most common and aggressive cancer that begins within the brain. Without treatment the average survival following diagnosis is merely 3 months. Although clinically-approved kinase inhibitors present promising features to treat GBM, most of them do not cross the blood brain barrier (BBB), impeding their clinical use in GBM patients. We propose an agile approach that combines ligand-based drug design of highly-focused compound libraries and first-in-class phenotypic assay for simultaneous screening of BBB penetration, unspecific toxicity and anticancer properties, in an iterative manner. This approach will allow a one-step selection of hit / lead compounds from in-house generated compound libraries that cross the BBB to accelerate the design of CNS-active anticancer drugs. Furthermore, the use of chemical proteomics and the state-of-the-art proteomics techniques will facilitate the identification of the kinases and / or pathways that are involved in the observed phenotype, which could result in the discovery of novel GBM oncotargets and unknown modes of action. This highly innovative integrated approach has the potential to speed up preclinical drug discovery efforts in CNS diseases, and in doing so, promote European Scientific Excellence. As a developer and provider of such tools, the applicant will be positioned in a privileged position for starting cross-disciplinary collaborations with academics and Pharma across Europe and for establishing herself as an independent researcher.

Keywords: glioblastoma multiforme,kinase inhibitors,phenotypic screening,brain penetrant drugs,ligand based drug design
Innovation Support services by EEN for Enhancing the Innovation Management Capacity of Bulgarian SMEs (EEN-BG InnoSupp)

Framework: Horizon 2020 — Industrial Leadership
Programme: Innovation in SMEs
Action type: Specific Grant agreement
Countries involved: Bulgaria,Bulgaria,Bulgaria,Bulgaria,Bulgaria,Bulgaria,Bulgaria,Bulgaria
Call: Enhancing the innovation management capacity of SMEs (H2020-Adhoc-2014-20, 2014)
Start date: 2015-01-01
End date: 2016-12-31
Duration (months): 24.0
Total project cost (EUR): 117929.0
EU funding (EUR): 117929.0
Participants: 12
Project status: CLOSED

The EEN-BG InnoSupp project outlines the scope and services of Work Package 4 (WP4/Activity 4) of the EEN-Bulgaria Implementation Strategy. The overall project objective is to enhance the innovation management capacity of SMEs. It is broken down into the following specific objectives: (i) support the SMEs that are beneficiaries of the SME instrument in strengthening their innovation management capacity and enhancing their overall innovation efficiency throughout their project implementation; The Key Account Management (KAM) service foresees identifying gaps and needs in the innovation management domain, proposing the best match of a coach(es) and acting as mediator between the SME and innovation coach to address these gaps and needs; (ii) to enhance the innovation management capacity of Bulgarian SMEs by addressing gaps and needs with well-devised actions and measures towards increased efficiency and effectiveness of the innovation processes, and thus increased potential to benefit from the European support for research and innovation, in the scope of the ‘Enhancing Innovation Management Capacity – Innovation Expert’ services (EIMC). Within these services assessment of the innovation capacity of client SMEs will be done with the help of the IMP3rove tool. The Innovation Expert Team (IET) consists of 7 experts, 5 of whom are already licensed and trained in using the tool. The project envisages delivering 105 service packs to SMEs. All Bulgarian SMEs beneficiaries of the SME Instrument are entitled to receive the KAM services. Within the remaining service packs EIMC services will be delivered. Screening for prospective clients and beneficiaries for the EIMC services will be performed by all 12 EEN host organisations in their daily work, thus ensuring national coverage of the screening. With regards to the existing clients, the EEN hosts are assumed to have insight to their capacity and needs. Potential clients identified by EEN-Bulgaria will be signposted to the IET.

Keywords: innovation support
Multi-perspective Ultrasound Strain Imaging & Elastography (MUSE)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Starting grants
Action type: ERC actions
Panel: Systems and communication engineering
Panel description: Electrical, electronic, communication, optical and systems engineering
Countries involved: Netherlands
Call: ERC Starting Grant (ERC-2017-STG, 2017)
Start date: 2018-02-01
End date: 2024-01-31
Duration (months): 72.0
Total project cost (EUR): 1998504.75
EU funding (EUR): 1998504.75
Participants: 1
Project status: SIGNED

Ultrasound (US) is the modality of choice for imaging and functional measurements of the cardiovascular system due to its high spatial and temporal resolution. In recent years, the use of US has been on the rise owing to huge advancements in acquisition speed and resolution. Nevertheless, because of physical constraints, several issues —limited field-of-view, refraction, resolution and, contrast anisotropy— cannot be resolved using a single probe. This proposal will aim at tackling these issues introducing Multi-perspective Ultrasound Strain Imaging & Elastography (MUSE). MUSE will push the frontiers of 3-D US imaging by introducing a novel, multi-perspective 3-D US system. The revolutionary system will consist of two synchronously controlled 3-D matrix arrays and advanced signal and image processing to improve geometric and functional measurements (strain, elasticity). Validation will be performed for two applications: cardiac strain imaging in patients with aortic valve stenosis (AoS) and elastography of abdominal aortic aneurysms (AAA). Fusion of dual-probe data will be challenged and achieved by new algorithms, preserving important features and improving both contrast and field-of-view. Advanced 3-D processing of the raw US data will be developed for motion and strain imaging. A novel compounding technique, fusion strain imaging, will combine multi-perspective strain data to improve accuracy and precision. A comprehensive framework for system verification and validation will be built, comprising US simulations, ex vivo experiments, and in vivo pilot studies on healthy volunteers. The proposed technique will be validated in AoS and AAA patients. Ultimately, MUSE will introduce a non-invasive, ground-breaking US platform for functional screening and follow-up, and a breakthrough in early diagnosis, clinical decision making, and risk assessment of cardiovascular disease. Moreover, MUSE has the potential to replace invasive or costly imaging modalities with US.

Keywords: ultrasound,multiview,fusion,strain imaging,elastography,biomechanics,heart disease,aneurysms
Metabolic regulation of metastatic growth (MetaRegulation)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Consolidator grants
Action type: ERC actions
Panel: Physiology in Health, Disease and Ageing
Panel description: Organ and tissue physiology, comparative physiology, physiology of ageing, pathophysiology, interorgan and tissue communication, endocrinology, nutrition, metabolism, interaction with the microbiome, non-communicable diseases including cancer (and except disorders of the nervous system and immunity-related diseases)
Countries involved: Belgium
Call: ERC Consolidator Grant (ERC-2017-COG, 2017)
Start date: 2018-06-01
End date: 2023-05-31
Duration (months): 60.0
Total project cost (EUR): 2000000.0
EU funding (EUR): 2000000.0
Participants: 1
Project status: SIGNED

Metastatic growth of cancer cells requires extracellular matrix (ECM) production. The current understanding is that transcription factors regulate ECM production and thus metastatic growth by increasing the expression of collagen prolyl 4-hydroxylase (CP4H). In contrast, we recently discovered that metabolism regulates CP4H activity independently of the known transcription factors. Specifically, we found that loss of pyruvate metabolism inhibits CP4H activity and consequently ECM–dependent breast cancer cell growth. Based on this discovery we propose the novel concept that metabolism regulates metastatic growth by increasing ECM production. In this project we will investigate the following questions: 1) What is the mechanism by which pyruvate regulates CP4H activity in breast cancer cells? To address this question we will investigate pyruvate metabolism and ECM production in 3D cultures of various breast cancer cell lines using 13C tracer analysis, metabolomics, and two-photon microscopy based ECM visualization. 2) How can this novel metabolic regulation be exploited to inhibit breast cancer-derived lung metastases growth? To address this question we will inhibit pyruvate metabolism in metastatic breast cancer mouse models using genetically modified cells and small molecules in combination with immuno- and chemotherapy. 3) How can this novel regulation be translated to different metastatic sites and cancers of different origin? To address this question we will determine the in vivo metabolism of breast cancer-, lung cancer-, and melanoma-derived liver and lung metastases (using metabolomics and 13C tracer analysis), and link it to ECM production (using two-photon microscopy based ECM visualization). With this project we will deliver a novel concept by which metabolism regulates metastatic growth. In a long-term perspective we expect that targeting this novel metabolic regulation will pave the way for an unexplored approach to treat cancer metastases.

Keywords: in vivo cancer metabolism,metastasis,metabolic regulation,extracellular matrix production
Membrane-based nano-mechanobiology: Role of mechanical forces in remodelling the spatiotemporal nanoarchitecture of the plasma membrane (NANO-MEMEC)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Advanced grants
Action type: ERC actions
Panel: Molecules of Life: Biological Mechanisms, Structures and Functions
Panel description: Molecular biology, biochemistry, structural biology, molecular biophysics, synthetic and chemical biology, drug design, innovative methods and modelling
Countries involved: Spain
Call: ERC Advanced Grant (ERC-2017-ADG, 2017)
Start date: 2018-12-01
End date: 2024-11-30
Duration (months): 72.0
Total project cost (EUR): 2212063.0
EU funding (EUR): 2212063.0
Participants: 1
Project status: SIGNED

Through evolution, cells have developed the exquisite ability to sense, transduce and integrate mechanical and biochemical signals (i.e. mechanobiology) to generate appropriate responses. These key events are rooted at the molecular and nanoscale levels, a size regime difficult to access, hindering our progress towards mechanistic understanding of mechanobiology. Recent evidence from my Lab (and others) shows that the lateral nanoscale organisation of mechanosensitive membrane receptors and signalling molecules is crucial for cell function. Yet, current models of mechanosensing are based on force-induced molecular conformations, completely overlooking the chief role of mechanical forces on the nanoscale spatiotemporal organisation of the plasma membrane. The GOAL of NANO-MEMEC is to provide mechanistic understanding on the role of mechanical stimuli in the spatiotemporal nanoarchitecture of adhesion signalling platforms at the cell membrane. To overcome the technical challenges of probing these processes at the relevant spatiotemporal scales, I will exploit cuttingedge biophysical tools exclusively developed in my Lab that combine super-resolution optical nanoscopy and single molecule dynamics in conjunction with simultaneous mechanical stimulation of living cells. Using this integrated approach, I will: First: dissect mechanical and biochemical coupling of membrane mechanosensing at the nanoscale. Second: visualise the coordinated recruitment of integrin-associated signalling proteins in response to force, i.e., mechanotransduction. Third: test how force-induced spatiotemporal membrane remodelling influences the migratory capacity of immune cells, i.e., mechanoresponse. NANO-MEMEC conveys a new fundamental concept to the field of mechanobiology: the roles of mechanical stimuli in the dynamic remodelling of membrane nanocompartments, modulating signal transduction and ultimately affecting cell response, opening new-fangled research avenues in the years to come.

Keywords: membrane organisation and signalling,nanoscale mechanobiology,integrin nanoassemblies,quantitative super resolution,single molecule fluorescence,shear flow,stretching,micro and nano patterning
BIOCOPY: the new biomolecule copying and screening solution for diagnostics and therapeutics (BIOCOPY)

Framework: Horizon 2020 — Industrial Leadership
Programme: Innovation in SMEs
Action type: SME instrument
Countries involved: Germany
Call: SME instrument (H2020-SMEInst-2018-2020-1, 2018)
Start date: 2018-06-01
End date: 2018-09-30
Duration (months): 4.0
Total project cost (EUR): 71429.0
EU funding (EUR): 50000.0
Participants: 1
Project status: CLOSED

BioCopy is a spin-off company borned in the University of Freiburg. We have developed an innovative, patented technique to copy biomolecules analogous to a photocopier. A DNA-coated surface is used as copy template. By supplying different biochemical "copy mixes", either a DNA, a RNA or a protein copy is generated. After the copy process, the copied biomolecules can be analyzed label-free for their specific binding to target molecules and recovered as potential candidates for a future use as therapeutics or diagnostics. The BioCopy technology completely opens up new dimensions for drug development, vaccines, antibodies, enzymes, catalysts, bioactive coatings, and biosensors and it has are more than 40 future applications. We plan to offer 3 products and services to pharma and biotech companies, related with high- output and cheaper molecular biology screenings. The most promising line is the tailor-made discovery of vaccine candidates within two days. This will have a disruptive character, because the first generation of a vaccine is a billion-dollar market, projected to rise $60 billion on 2019, with 11% growth per annum, and to $100 billion by 2025. BioCopy will provide vaccine candidates to pharmaceuticals, obtaining revenues through upfront, milestone and royalty payments, and they will be responsible for the vaccine´s clinical development, approval and distribution. The multi-awarded BioCopy team covers business know-how and expertise in biology, physics, manufacturing systems engineering, assay development and microsystems technology. BioCopy aims to contribute to the European challenges related with advanced biotechnology applications in pharma sector, and to increase the technological transfer from the academic world into the manufacturing sector. During phase 1 we will build up a detailed business plan and a feasibility study, describing all the needed activities in order to reach BioCopy commercialization. We will need about €2.5M in phase 2.

Keywords: proteins,biomolecules copying,biocopy,screening,vaccines,microarrays,aptamers,label free detection