Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet LQTS-HORSES (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

The Equine Cardiac Group at the University of Copenhagen has established a platform for diagnosing long QT syndrome (LQTS) in horses. In men, this condition is a cause of severe ventricular arrhythmias leading to death in some cases. The pathophysiological mechanism behind this disturbance of the cardiac rhythm is a delayed repolarisation often associated with reduced function of voltage gated potassium (K-) channels. LQTS is one of the cardiac causes of sudden death in athletes. Sudden deaths occurring during public events have a highly negative impact on the public perception about high performance sports, both in men and in horses, and raise concerns about animal welfare especially in the racing industry. With the new tools developed by the Equine Cardiac Group the presence of LQTS will be investigated in horses by screening ECGs from a large pool of horses with different genetic backgrounds. Genetic sequencing will be performed on blood samples from this population and from horses with sudden death to describe genetic polymorphisms or mutations in the K-channels. The identified equine sequences will be compared to those described for men and the function of the identified mutations will be characterized electrophysiologically using voltage-clamp techniques, generating then new insights into the pathophysiology of LQTS in horses. The benefit of the proposed project will be triple: 1) It will allow for identification of LQTS in horses and will aim at developing a reliable diagnostic test to screen horses for LQTS; 2) It will enable us to exclude them form racing and to reduce sudden deaths during sport events and therefore it will increase safety and animal welfare in racing industry, an important economic factor for many European areas; 3) Similitudes between men and horses in regard to the pathophysiology of LQTS might establish horses as a valuable model for investigating disturbances of repolarisation, especially those occurring in highly trained athletes.

Mots clés : equine, cardiology, repolarisation, long qt syndrome, sudden cardiac death, potassium channels

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 200194.8 €
Projet 3DHumanSpinalCord (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Organizers direct formation of the body, releasing morphogens to position tissues and organs. But what organizes the organizers? I aim to harness organizer formation to build self-patterning 3D human spinal cord in vitro. In developing spinal cord, the floorplate organizer secretes Sonic Hedgehog to direct ventral-dorsal patterning. Prof Tanaka (secondment) discovered how to recapitulate this in vitro: single mouse naïve pluripotent stem cells (PSCs) form neural tube organoids and an early pulse of retinoic acid prompts self-organization of floorplate that drives patterning as in vivo. However, attempts to form cognate human organoids have been unsuccessful. There is a restricted window of competence to initiate floorplate formation, which conventional primed human PSCs are unable to access. To overcome this, I will combine microenvironment bioengineering with new naïve human iPSCs (Prof Elvassore, host) to recapitulate and study human development from an earlier stage, gaining access to molecular events that may underpin later fate specification and tissue organization. By mechanistic analysis in mouse organoids, I will reveal how competence is instated, how it is closed, and how to prolong or re-instate competence de novo. This knowledge will guide me in unlocking the competent state for human PSCs in vitro, and has implications for activating spinal cord regeneration in vivo. By use of sophisticated engineering technologies pioneered in the Elvassore group, I will control the micro-environment to guide tissue growth and formation, mimicking natural physiology and ensuring reproducibility. By engineering 3D organized human spinal cord in vitro, this project will bridge basic knowledge of critical and inaccessible stages of human development with future biomedical applications. This interdisciplinary training opportunity will build on my doctoral expertise in PSC identity transitions, setting me apart with a strong independent niche for my future career.

Mots clés : microenvironment bioengineering, microfluidics, organizers, spinal cord patterning, organoids

Participants :
- University of Padua (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 171473.28 €
Projet FOOTLOOSE (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Organofluorine compounds are highly sought after owing to diverse and numerous applications that take advantage of the unique properties imparted by the presence of one or more C–F bonds. The chemical stability and conformational landscape of molecules, together with the small size of the fluorine atom, has the made the replacement of a C–H or C–OH bond with a C–F one of the most rewarding modifications during the hit-to-lead stage in medicinal chemistry programs. Because many applications are dependent on the absolute and relative configuration of the fluorine-containing group, methods that can introduce such groups in a stereoselective manner are particularly attractive. The host laboratory has shown that substituted carbon chains can be grown one carbon atom at a time with exquisite control of relative and absolute configuration through iterative homologation of boronic esters with stereochemically-defined lithiated carbamates or benzoates. The latter are formed at low temperature, either through sparteine-mediated enantioselective deprotonation of primary carbamates/benzoates or the enantiospecific deprotonation or tin–lithium exchange of enantiomerically pure secondary carbamates/ benzoates. Although the process works well for extending a carbon chain with incorporation of carbon-based substituents, the incorporation of carbon atoms bearing electronegative substituents, such as oxygen- or fluorine-containing groups, is challenging. Herein we propose a programme of research to investigate the preparation of enantiomerically enriched organofluorine molecules, specifically those containing trifluoromethyl groups, through lithiation–borylation. The challenges outline above would make such a programme the ideal sharpening stone for the further development of lithiation–borylation. Indeed, a protocol that can introduce carbon atoms bearing electronegative groups would bring us a big step closer to assembly-line synthesis being able to make any molecule.

Mots clés : organofluorine, organoboron, carbanions, homologation, boronic esters, lithiated carbamate, trifluoromethyl, lithiation borylation, trifluoromethyl epoxides

Participants :
- University of Bristol (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet BOMB (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Information Science and Engineering
Statut du projet : CLOSED

Orthopaedic and dental implants are commonly used clinically. Their success rely on adequate primary and secondary stabilities, the latter being achieved through osseointegration, where bone grows around and onto the surface of the implant. However, prosthesis anchorage failures are still experienced and remain difficult to anticipate. The biomechanical properties of the bone-implant interface are the essentials for determining the implant stability but are still poorly understood. The objective of BOMB is to better understand the multiscale evolution of the biomechanical properties of the bone-implant interface with the overall aim to improve the long-term stability of implants. The project will use and further develop a standardized implant model of the host team to limit the influence of the implant geometry on osseointegration. Animal experimentation on rabbit and sheep will enable to work in a controlled as well as enhanced environments, using bone marrow stem cells, which are thought to be a promising new therapeutic tool to boost implant integration and hence improve implant stability. BOMB will combine the latest and advanced multimodal techniques spanning the nano and micro-scale to explore the structural and mechanical properties of the interface on a same sample. For instance, neutron high-resolution micro-tomography, a technique adapted to the presence of metallic components, has barely been applied on bone and will enable investigation of the microstructural properties of the interface. A successful completion of BOMB would represent a major step forward our limited understanding of the bone-implant biomechanical behaviour. This will lead to the development of new models, regenerative strategies as well as new implants to improve dental and orthopaedics solutions, and contribute to an increase of the life span of prostheses to ensure patients comfort and restoration of their daily life activity.

Mots clés : biomechanics, engineering, imaging, bone, implant, osseointegration, multiscale, tomography, neutron, diffraction, histology, nanoindentation

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 173076.0 €
Projet ChondroGEL (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Osteoarthritis (OA) is a type of joint disease that results from breakdown of cartilage and subsequent damage to the underlying bone. Polymeric biomaterials have rapidly expanded to promote cell differentiation and tissue regeneration, and are uniquely placed to provide sophisticated solutions for the treatment of OA. Among them, hydrophilic, biocompatible 3D networks, called hydrogels, represent the gold standard for tissue regeneration, owing to their high-water content and tuneable mechanical properties. However, incorporation in hydrogels of proteins and growth factors that are essential to induce tissue differentiation, is not trivial. By merging advanced hydrogel technology and cutting-edge cell biology research, we propose to develop a novel in situ protein-based crosslinked hydrogel system based on chondrogenic bioconjugates for controlled cellular differentiation. This unique approach allows for non-surgical administration of hydrogels with controlled and tuneable mechanical properties that retain their protein cargo at the treatment site. Furthermore, as the hydrogel is directly built from the required growth factors, even distribution throughout the macromaterial is ensured. This new treatment modality will allow for both short-term relief of pain through mechanical support of the inflamed joint, while providing important biological cues for the differentiation of administered stem cells into chondrocytes for cartillage repair. Furthermore, the implementation of a fluorescence life-time imaging microscopy (FLIM) approach for monitoring changes in cell behaviour will allow for rapid identification of lead materials significantly earlier in the development pipeline than is currently available through conventional methods. While this work is focused on developing hydrogels for cartilage repair, it is envisaged that the knowledge and experience gained throughout this project will allow for other therapeutic targets to be explored in the future.

Mots clés : hydrogels, stem cell therapy, cell differentiation, cartilage regeneration

Participants :
- University of Birmingham (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €
Projet SpatialArth (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Osteoarthritis (OA) is the most prevalent chronic musculoskeletal disorder causing pain, morbidity and disability, giving rise to enormous healthcare expenditures and loss of work. The exact triggers and pathogenesis of OA are still poorly understood. Currently, there are no measures to slow down the progression of OA. Bulk tissue-based multi-omics and small-scale single cell RNA-seq studies focussing on chondrocytes and synoviocytes have identified novel cell clusters, supporting the hypothesis that OA is a disease of the whole joint. However, one of the key relevant tissues (bone) have not yet been studied. In addition, approaches to date have employed lengthy live cell extraction approaches that affect the transcriptome pattern. Finally, the spatial dimension of molecular changes in the osteochondral unit has not been studied to date. This work will fill this fundamental gap in our understanding of the molecular aetiopathogenesis and progression of OA by employing a novel cutting-edge technique, spatial transcriptomics (ST). ST acts like a high-throughput molecular microscope to allow visualisation and quantitative analysis of the transcriptome with spatial resolution in individual tissue sections, affording near-single cell resolution. SpatialArth will generate new knowledge on the molecular profile of the osteochondral unit and will identify with spatial resolution which cells are involved in the pathogenesis of OA. I will combine ST sequencing and protein expression data from cartilage and bone tissues from OA patients (matched tissues from intact and degraded regions of tibial plateau) and tissues derived from non-OA knee joints. Additionally, I will develop my computational genomics skillset, aiming to help fill the need for a much-needed next generation of interdisciplinary researchers. SpatialArth addresses several mandatory European Union calls - finding strategies supporting healthy and active aging and decreasing the economic burden on healthcare.

Mots clés : spatial transcriptomics, knee osteoarthritis, cartilage, subchondral bone, multi omics

Participants :
- Helmholtz Zentrum München (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 174806.4 €
Projet ChondUb (Horizon 2020, appel à projets 2015)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Osteoarthritis (OA), characterised by cartilage degradation, is the most common form of arthritis affecting >10% of the EU population over 60 years of age. The pathogenesis is only poorly understood. There is no cure available and current treatment involves pain relief and joint replacement surgery. WWP2 is an ubiquitin ligase involved in stem cell differentiation, cancer development and immune responses, and importantly plays crucial roles in chondrogenesis and craniofacial development. However, its role in cartilage biology and OA development has not been elucidated. Ubiquitination regulates most signalling pathways and cellular processes. Previously, I have shown that ubiquitination plays a role in OA development. Here I aim to identify and characterise WWP2 substrates using a combination of novel techniques. In addition, I will investigate the role of WWP2 and its substrates in cartilage biology with the goal to uncover molecular targets for OA treatment and other WWP2-related diseases. The project is aligned with the “Health, Demographic Change and Well-Being” and “Understanding disease” challenges of Horizon2020. The work will be performed under supervision of Dr Weissman, Chief of the Laboratory of Protein Dynamics and Signaling at the National Cancer Institute (US) and at “EULAR Centre of Excellence” at Newcastle University (UK) under supervision of Prof Young. Dr Weissman has an excellent track record in ubiquitin ligases biology and development of drugs targeting them and Prof Young in cartilage biology and mouse models of OA. Therefore, both groups are highly complementary for this project and envisage future collaborations arising from this fellowship. During this multidisciplinary project I will acquire new knowledge and will reinforce my research skills by learning novel techniques. It is a great opportunity to conduct a creative and independent research facilitating achievement of my main career goal to become an independent research group leader.

Mots clés : chondrocyte, osteoarthritis, ubiquitination

Participants :
- Newcastle University (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 171792.6 €
- Government of the United States of America (Etats-Unis) — Partner, organization partner, Organismes publics (hors enseignement & recherche), subvention : 0.0 €
Projet PRINT-CHEMO (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Osteosarcoma is the most commonly diagnosed bone tumour with most of these cases being in children and adolescents. Each year over 4,000 new cases of osteosarcoma are diagnosed in the United States. Osteosarcoma predominantly initiates in the metaphysis of long bones, such as the distal femur, proximal tibia and proximal humerus. Over 50% of these tumours are relatively resistant to radiation therapy, due to the molecular aberration of the tumour. The current gold standard for treatment is tumour resection and adjuvant chemotherapy, with a 5-year survival rate of 61.6% in patients aged 0-24 years old. Approximately one-third of patients diagnosed with osteosarcoma are expected to have a relapse, with only 15% of these patients surviving the disease a second time. Therefore, due to the young age of initial diagnosis, the management of this disease is a challenging and costly exercise, which has a significant socioeconomic cost, estimated to be €14.7 billion in Europe and $45 billion in the USA in the last 18 years. While significant progress has been made in trying to understand the intra-tumour heterogeneity and the evolutionary pattern of a subset of clones within the tumour, thus far, no major changes in treatment and outcome have been achieved. The hypothesis of PRINT-CHEMO is that localised delivery of self-assembled dendritic nanoparticles used as a first wave of treatment to deliver miR-194, a tumour suppressive gene, to the cells along with the delivery of nanoparticles loaded with chemotherapeutics would lead to higher survival rates and less side effects than systemic delivery of a higher dose of drug. Furthermore, PRINT-CHEMO not only aims to treat the diseased tissue but using 3D printing provide the necessary cues to allow for the body to regenerate the damaged bone caused due to tumour resection.

Mots clés : 3d bioprinting, nanotechnology, drug delivery, osteosarcoma

Participants :
- Mass General Brigham (Etats-Unis) — Partner, organization partner, Recherche, subvention : 0.0 €
- Trinity College Dublin (Irlande) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 257561.28 €
Projet CerQUIT (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

Our modern society and economy depend upon the constant, high-speed transmission and processing of information. Since every instance of computation or communication is realised by some physical device, it is the laws of physics that set the ultimate limits on performance. Applying this reasoning to quantum theory has led to a plethora of algorithms and protocols that achieve previously impossible levels of computational power and security. Realising the full promise of quantum information technologies will require theoretical tools, tailor-made to specific applications, which quantify the performance of a given protocol in a manner that is practical, efficient and satisfying to a sceptical end-user. This problem is particularly pressing in systems that admit a formal description only in terms of infinite dimensions. Experimental progress in such systems has shown them to be extremely promising as quantum technology platforms, but the technical difficulties in the analysis have severely constrained their application for cryptographic and information processing applications. This proposal aims to significantly advance the state-of-the-art in the theoretical understanding of quantum mechanical systems in infinite dimensions. I intend to design innovative and efficient tools for the characterisation of quantum states and processes. Here there will be two complementary foci: the theoretical rigour and direct operational interpretation necessary for cryptographic and computational applications; and direct experimental applicability, in the sense of proposing techniques that are ‘laboratory-ready’. I will then apply these tools to specific applications in secure communication and computation. These tools will be adapted to specific protocols and physical systems to maximise efficiency and performance in large-scale, networked architectures. Finally, the analysis will be applied to uncovering new protocols for quantum enhanced simulation and computation.

Mots clés : quantum tomography, quantum information, quantum cryptography, many body systems, quantum computation

Participants :
- Freie Universität Berlin (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 171460.8 €
Projet COLOSSEO (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Environment and Geosciences
Statut du projet : CLOSED

Over the past decade (1999-2009), earthquakes proved to be the deadliest of all European disasters. Italy is one of the most seismically active countries in Europe and, Southern Italy, is recognized as the most seismically active sector of the peninsula. The sector is traversed by the Apennine fold-and-thrust belt which is seismogenic, along the Outer Front, in northern-central Italy and in Sicily. On the contrary, it is considered often inactive in southern Italy. Nevertheless, historical seismicity reports several destructive earthquakes and geological-geomorphological indications of recent deformation have been recently pointed out. The geological setting contrasts the recognition of the seismogenic sources since the Apennine Outer Front is buried under Plio-Quaternary foredeep successions. It is urgent to develop new approaches to investigate the active deformation in this sector. This research aims to detect evidence of Late Quaternary active compressional faulting along the Southern Apennine Outer Front. The peculiar geological setting of the sector necessarily requires a multidisciplinary approach. The research plan envisages the integration of HRT (high resolution topography) data analysis, morphotectonic analysis in GIS/Matlab environments, geochronologic dating and classical methodologies of analysis belonging the seismotectonics. Airborne lidar topographic data are able to capture fault offsets and landscape properties recording the complexity and sensitivity of deformation. The drainage pattern analysis and morphometric indices computed using GIS (Geographic Information System) and Matlab programming language are suitable for evaluating the effects of active tectonics on the topography or morphological features. These novel approaches are exploding worldwide. Exploiting them in order to investigate the active deformation represents an excellent chance to improve the knowledge on the southern Apennines seismotectonic setting.

Mots clés : active tectonics, earthquake hazards, lidar, geomorphic metrics, tectonic geomorphology, southern, apennines, italy

Participants :
- Arizona's Public Universities (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- University of Chieti-Pescara (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 262269.0 €