Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Deciphering the role of astrocytes in chronic depression. (ASTRO_ECM)

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-2017, 2017)
Start date: 2018-05-01
End date: 2020-04-30
Duration (months): 24.0
Total project cost (EUR): 159460.8
EU funding (EUR): 159460.8
Participants: 1
Project status: CLOSED

Depression is a debilitating psychiatric disorder that affects 1 in 7 people worldwide. Despite coordinated efforts from researchers and clinicians alike, the neurobiological substrates of depression remain largely unknown. As a result, therapeutic options against depression are inadequate. Using a valid preclinical model, I recently demonstrated that depression alters the molecular composition of astrocytes and the organization of extracellular matrix (ECM), an assembly of molecules that are primarily synthesized and released by astrocytes. This results in disrupted information relay in the hippocampus and in cognitive impairment, both commonly seen in depressed patients. Thus, my work suggests a role of astrocytic (dys)function in the depressive state. In the proposed project, I aim to unravel the contribution of astrocytes in the pathophysiology of depression. First, I will address how the depressive state affects astrocyte proteome, morphology and function. Second, I will address the role of astrocytes and astrocyte-derived ECM in the manifestation of depression at the molecular, cellular and the behavioural level. To reach my goals, I will make use of genetically engineered mice that allow for visualization, metabolic labeling and targeting of astrocytes. These mice will be subjected to social defeat to induce a chronic depressive state. I will study astrocyte morphology, physiology and proteome alterations in depressed mice vs. controls. After establishing astrocyte-specific changes, I will employ i) viral vector-assisted silencing of the expression of astrocytic genes contributing to the ECM and ii) designer receptor exclusively activated by designer drugs (DREADDs)-assisted modulation of astrocyte activity. I will then assess whether these interventions can ameliorate the depressive state. With this integrative approach I aim to uncover novel molecular pathways mediating the depressive state and to identify new targets for the treatment of depression.

Keywords: depression,hippocampus,astrocyte,extracellular matrix
Spatial-temporal characteristics of Cortical Reorganization after Spinal Cord Injury and the role of interneurons and astrocytes (CRASCI)

Framework: Horizon 2020 — Excellent Science
Programme: Marie-Sklodowska-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Individual Fellowships (IF)-Society and Enterprise panel
Action type: Marie Skłodowska-Curie actions
Panel: Life Sciences
Countries involved: Spain
Call: Individual Fellowships (H2020-MSCA-IF-2017, 2017)
Start date: 2018-08-01
End date: 2021-04-20
Duration (months): 24.0
Total project cost (EUR): 170121.6
EU funding (EUR): 170121.6
Participants: 1
Project status: CLOSED

Spinal cord injury (SCI) is followed by functional reorganization of the primary somatosensory cortex (S1), in which the S1 area deprived of inputs is activated by sensory stimulation of surrounding intact regions. Recent data suggest that reorganization after SCI is a heterogeneous process depending on the time elapsed after injury and the cortical layer under study. This research proposal aims to study the complexity of the cortical reorganization after SCI in terms of spatial-temporal patterns and the involvement of distinct cell types as inhibitory interneurons and astrocytes. This will be achieved by monitoring and manipulating brain activity using in vivo and in vitro electrophysiology, genetically encoded calcium indicators (GCaMP6), chemogenetics (DREADDs) and transgenic mice. A mice model of thoracic SCI will be used throughout the study. First, reorganization of the hindlimb and forelimb S1 cortex at different time points after the injury will be studied by recording in vivo neuronal activity in response to sensory stimulation across all layers of S1 using a vertical multielectrode array. Second, changes in inhibitory transmission induced by SCI will be studied by monitoring intracellular Ca2+ signaling and by in vitro electrophysiology from GFP expressing GABAergic cells. Third, the role of astrocytes in the reorganization after SCI will be studied by using either Gq DREADD to enhance astrocyte activity or IP2R2-/- mice to decrease astrocyte activity while recording in vivo neuronal responses across all layers of S1. Changes in astrocyte activity after SCI will also be determined by monitoring intracellular Ca2+ signals from astrocytes expressing the calcium indicator GCaMP6. Results from this proposal will be a first in understanding the complex network of local plasticity in S1 both in control conditions and after SCI. It will be also relevant to design new therapies for SCI-associated pathologies as neuropathic pain.

Keywords: cortical plasticity,spinal cord injury,inhibitory interneurons,astrocytes,neuronal excitability
A novel approach for modeling development of breast cancer (BRCANCER)

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: Australia,Netherlands
Call: Marie Skłodowska-Curie Individual Fellowships (IF-GF) (H2020-MSCA-IF-2015, 2015)
Start date: 2016-01-04
End date: 2018-07-03
Duration (months): 30.0
Total project cost (EUR): 207584.4
EU funding (EUR): 207584.4
Participants: 2
Project status: CLOSED

Inheriting one mutant copy of the BRCA1 or BRCA2 gene is associated with a significant increased risk for developing aggressive and difficult to treat breast cancer, the most common cancer type in women worldwide. Despite previous efforts to recapitulate tumorigenesis with the use of mouse models and cancer cell lines, the exact mechanisms that underlie BRCA1 or BRCA2-dependent tumor development remain unclear. Recent advances in stem cell culturing have enabled long-term expansion of in vitro human breast organoids or ‘mini-breasts’. In a novel approach, this state-of-the-art culture technology will be used together with CRISPR/Cas9-mediated gene-editing and human-in-mouse xenografts to prospectively recapitulate early breast cancer development. Results of the study will generate novel fundamental insight into the development of breast cancer, support the development of personalized medicine using laboratory models, and aspires to identify novel breast cancer biomarkers and treatment strategies. The expertise of the laboratory of H. Clevers, who pioneered the organoid methodology and works at the top of the field of stem cell biology, will be combined with the expertise of the research group of J. Visvader and G. Lindeman, world leaders in the field of breast cancer research and experts in the methodology of mammary xenotransplantation. This unique setting forms an excellent envorinment for my postdoctoral research training, allows extensive knowledge exchange and provides opportunities for novel research lines and collaborations.

Keywords: breast cancer,organoids,brca1,brca2,xenotransplantation
Integrating innovative TECHnologies along the value Chain to improve small ruminant welfARE management (TechCare)

Framework: Horizon 2020 — Societal Challenges
Programme: Food security, sustainable agriculture and forestry, marine and maritime and inland water research and the bioeconomy
Theme: Sustainable agriculture and forestry
Action type: Innovation actions
Countries involved: Italy,Spain,Ireland,Israel,Italy,Spain,Greece,Romania,Norway,France,France,France,France,France,France,United Kingdom,United Kingdom,United Kingdom
Call: Improving animal welfare (H2020-SFS-2019-1, 2019)
Start date: 2020-09-01
End date: 2025-08-31
Duration (months): 60.0
Total project cost (EUR): 5999895.0
EU funding (EUR): 5703693.01
Participants: 24
Project status: SIGNED

TechCare is a multi-actor approach project aiming to develop appropriate business models using innovative technologies to improve welfare management for all EU small ruminant (SR) systems, to enable stakeholders to choose animal welfare-friendly products. SRs play a key socio-economic role in Europe, especially in harsh environments where innovative technology is not much implanted. SRs are often managed as a flock/herd, allowing only average welfare states to be considered. Innovative technologies are a unique opportunity to monitor and improve SR welfare management at the individual or flock/herd level, along the value chain. Based on SR welfare state-of-the-art, TechCare will undertake a multi-actor approach to encapsulate stakeholders’ expectations in terms of welfare and innovative technologies, and provide them with adapted solutions, in a co-design approach. TechCare will cover all stages of SR production and build novel welfare approaches to develop and validate tools, early warning systems, algorithms and indicators for efficient identification of welfare issues, including positive welfare, to include them in welfare management models. The innovative technologies identified in TechCare will pass different stages of validation, from prototyping to large scale studies. TechCare identified solutions will therefore be replicable and adapted to different SR systems, production purposes, and value chains, for improvement of SR welfare management EU-wide. Business models will be constructed and validated with stakeholders. Dissemination, communication and exploitation materials will be produced and widely shared for easy use of TechCare solutions, ensuring their uptake and relevance to all sectors and stakeholders. TechCare will offer a durable improvement of SR welfare management using innovative technologies along the whole value chain and across the EU, and will act as an example in terms of approach and solutions for other species and production systems.

Keywords: small ruminant
Solid-phase synthesis of imprinted nanoparticles exhibiting glycan epitope recognition in glycoproteins (SSINGERG)

Framework: Horizon 2020 — Spreading excellence and widening participation
Programme: Widening participation and spreading excellence
Theme: Other Widening
Action type: Marie Skłodowska-Curie actions
Countries involved: Portugal
Call: Widening Fellowships (H2020-WF-01-2018, 2018)
Start date: 2019-10-01
End date: 2021-09-30
Duration (months): 24.0
Total project cost (EUR): 147815.04
EU funding (EUR): 147815.04
Participants: 1
Project status: CLOSED

The present project aims at the preparation of synthetic nanoreceptors exhibiting glycan epitope recognition in glycoproteins, identified to play a critical role in cell biology and diseases. Such nanoreceptors, behaving like antibodies, may cope with the current limitations in the essential step of enrichment of specific glycan subclasses, within studies of the glycoproteome. The preparation of the receptors will proceed through solid-phase synthesis of imprinted polymer nanoparticles, with the potential to deliver entities with size, specificity and solubility characteristics comparable to antibodies. The solid-phase synthesis of NanoMIP will require the immobilization of important monosaccharides (N-acetylglucosamine, N-acetlgalactosamine, mannose), widely found in glycoproteins, onto supporting beads. Several synthetic routes will be studied for the immobilization onto silica or plastic beads . In a reactor, built as a controlled temperature glass column filled with the beads containing immobilized monosaccharide, criteriously selected polymerization or sol-gel mixtures will generate the nanoMIPs, with subsequent selection of the highest affinity particles. The optimum combinations of solid-phase/imprinting protocol will be screened from a myriad of nanoMIPs prepared in different conditions. The performance of the nanoMIPs will be ascertained by setting a competitive enrichment protocol consisting of the incubation with a mixture of N-acetylglucosamine-, N-acetylgalactosamine- and mannose-containing glyproteins and a non-glycoprotein. Sorption isotherm data will be used to derive important binding features such as capacity, binding affinity and selectivity. Patentable robust solid-phases and imprinting protocols, either in standalone or combined manner, are planned outputs of the project, which may, in the near future, be incorporated into existing automated solid-phase synthesis instrumentation, for increased throughput and batch reproducibility.

Keywords: molecularly imprinted polymer,plastic antibodies,epitope recognition,solid phase synthesis,nanomips
Synthetic biology of non-ribosomal peptide synthetases to generate new peptides (SYNPEP)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Advanced 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: Germany
Call: ERC Advanced Grant (ERC-2018-ADG, 2018)
Start date: 2019-10-01
End date: 2024-09-30
Duration (months): 60.0
Total project cost (EUR): 3165788.0
EU funding (EUR): 3165788.0
Participants: 1
Project status: SIGNED

Natural products (NPs) generated by microbial non-ribosomal peptide synthetases (NRPS) represent several very important and valuable clinical antibiotics, immune-suppressive and anti-cancer drugs. NPs have gone on to inspire several synthetic peptides that are used clinically, but contain amino acids (AAs) or other building blocks that are not found in nature. However, with >500 identified AAs and additional peptide modifications like glycosylation or cyclization, the chemical diversity in NRPS-derived peptides is far larger than proteins and has not yet been fully explored. The modular nature of NRPS suggests the possibility to manipulate them, subsequently leading to the production of non-natural NPs. With an eXchange Unit (XU) concept, developed in Photorhabdus, Xenorhabdus and Bacillus, we have recently identified efficient ways for NRPS manipulation enabling the de novo assembly of novel NRPS for the production of new-to-nature NPs in excellent production yields of >250 mg/L. Within SYNPEP we will expand this approach to other bacterial genera producing peptide NPs. We will identify unusual NRPS systems, analyse them bioinformatically, validate the function of novel NRPS units experimentally and combine high-throughput molecular biology, microfluidics for bioactivity screening, rapid NP identification and structure elucidation to produce potentially any peptide or a peptide library of 2-15 amino acids in <4 weeks, in a semi-automated manner. In contrast to chemical peptide synthesis this production pipeline is more economical, sustainable and scalable. The NPs are produced by bacterial cells in aqueous media using cheap energy sources and the bacterial cultures can be easily scaled up when larger NP amounts are needed. We will also develop NRPS units that accept synthetic building blocks currently not found in natural NRPS. These ‘synthetic’ NRPS units will enable the simplified chemical derivatization of the produced NPs for further compound diversification.

Keywords: bioactive natural products,peptides,bioactivity screening,drug development,in vitro peptide production
New method to mechano-spectroscopically investigate the transient evolution of a complex-fluid's microstructure subjected to a non-linear deformation or flow (OrthoChirp)

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: Physics
Countries involved: Belgium
Call: Individual Fellowships (H2020-MSCA-IF-2018, 2018)
Duration (months): 24.0
Total project cost (EUR): 178320.0
EU funding (EUR): 178320.0
Participants: 1
Project status: CLOSED

The purpose of this project is to demonstrate a proof-of-concept for a novel and universal method to mechano-spectroscopically investigate transient evolution of a complex-fluid's microstructure when subjected to a non-linear deformation or flow. Dr Victor Boudara will pursue this goal at the Department of Chemical Engineering of KU Leuven, under the supervision of Prof Christian Clasen. The goals of the project will be achieved by combining an optimized excitation signal structure (as recently introduced with the novel "Optimally Windowed Chirp" technique) with the concept of orthogonal superposition rheometry. The possibility to superpose such a rapid mechano-spectroscopy onto deforming system would allow, for the first time, to characterise the material property evolution of rapidly mutating materials over a wide range of frequencies under nonlinear shear flow. Such materials include gelling polymers, proteins, colloidal gels or jamming glasses, which are not only of fundamental but also of industrial and biomedical interest.

Keywords: rheometry,rheology,soft matter,complex fluids
Schwann Cell Options for chronic Pain Eradication (SCOPE)

Framework: Horizon 2020 — Excellent Science
Programme: European Research Council (ERC)
Theme: European research council
Destination: Advanced grants
Action type: ERC actions
Panel: Prevention, Diagnosis and Treatment of Human Diseases
Panel description: Medical technologies and tools for prevention, diagnosis and treatment of human diseases, therapeutic approaches and interventions, pharmacology, preventative medicine, epidemiology and public health, digital medicine
Countries involved: Italy
Call: ERC Advanced Grant (ERC-2018-ADG, 2018)
Start date: 2019-09-01
End date: 2025-02-28
Duration (months): 66.0
Total project cost (EUR): 2185921.0
EU funding (EUR): 2185921.0
Participants: 1
Project status: SIGNED

Chronic pain, characterized by increased sensitivity to innocuous/mild stimuli (allodynia), afflicts 25% of the European adult population. Efficacy and/or safety of analgesic medicines is limited, and the treatment of chronic pain associated with inflammation, peripheral and central neuropathies and cancer remains unsatisfactory. Thus, identification of novel targets for better and safer analgesics is a major medical need. Transient receptor potential ankyrin 1 (TRPA1) channel, expressed by a subpopulation of primary sensory neurons (nociceptors), has been proposed as a major transducer of acute pain. We have, recently, identified that TRPA1 is expressed in Schwann cells that ensheath peripheral nerve fibres. In a prototypical model of neuropathic pain (sciatic nerve ligation in mice), we discovered that Schwann cell-TRPA1 exerts a hitherto unknown role that, via amplification of the oxidative stress message, sustains neuroinflammation and chronic pain (allodynia). Thus, Schwann cells, through their own repertoire of channels and enzymes orchestrate in the injured/inflamed tissue an autocrine/paracrine signalling pathway to sustain chronic pain. The purpose of the present project is to extend this observation to other models of inflammatory, neuropathic and cancer pain to identify a general paradigm based on Schwann cell/TRPA1/oxidative stress as the pathway that sustains chronic pain. We aim also at identifying in oligodendrocytes (the Schwann cells of the brain) whether the TRPA1/oxidative stress pathway sustains pain in the central nervous system. In mouse, rat and human Schwann cells/oligodendrocytes we aim at identifying biomarkers and combine them into biosignatures predictive of the susceptibility to the development of chronic pain. We anticipate that each molecular step that entails the TRPA1/oxidative stress pathway in Schwann cell lineages is an eligible target for discovering new effective and safer medicines for the treatment of chronic pain.

Keywords: transient receptor potential ankyrin 1 trpa1 channel,transient receptor potential vanilloid 4 trpv4 channel,chronic pain,oxidative stress,schwann cells,oligodendrocytes,macrophages,g protein coupled receptors gpcrs
new machine tool for SimultaneOus pLate beVElling on all material types (SOLVE)

Framework: Horizon 2020 — Industrial Leadership
Programme: Nanotechnologies, Advanced Materials, Advanced Manufacturing and Processing, and Biotechnology
Theme: Nanotechnologies
Action type: SME instrument
Countries involved: Italy
Call: Accelerating the uptake of nanotechnologies advanced materials or advanced manufacturing and processing technologies by SMEs (H2020-SMEINST-1-2016-2017, 2016)
Start date: 2016-06-01
End date: 2016-09-30
Duration (months): 4.0
Total project cost (EUR): 71429.0
EU funding (EUR): 50000.0
Participants: 1
Project status: CLOSED

Founded in 1963 in Reggio Emilia (Italy), our company OMCA SRL (www.omcasrl.it) has grown to become one of Europe’s leading manufacturers of bevelling and chamfering machines (i.e. “cutting” angled edges), mainly used in construction, mining and shipbuilding industries. Our continuous investment in advanced technology and our commitment to quality and customer service has helped solidify our position as one of Europe’s leaders with approximately 10% market share and €2M in annual revenues. This project, known as SOLVE (simultaneous plate bevelling), provides an optimum quality and a significant throughput improvement that will decrease bevelling times by 50% compared with current market offerings. We have invested so far €175,000 in validating and testing our First Prototype (10kW engine power) in a controlled environment (TRL6). Our preliminary market research also indicates that the increase in productivity for our clients address a core need that will provide them with a clear operational advantage over their competitors. For our company, we expect Solve to further solidify our position as a leading player in the bevelling machine tool industry and provide us an estimated 60% increase in sales revenues, resulting in a total revenue of €3.2M by 2021.

Keywords: chamfer,bevel,machining,machine tool,set up,productivity,efficiency