Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet PICModForPCa (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Information Science and Engineering
Statut du projet : SIGNED

Prostate cancer (PCa) is a major health problem among ageing men worldwide, especially in Europe. However, the medical management of PCa only offers limited individualisation and has led to significant overtreatment and undertreatment, which may compromise patient quality of life and survival respectively. Active surveillance is a clinical strategy in which patients with life-threatening PCa are directed to treatment while those with indolent tumours remain closely monitored via regular clinical tests and medical imaging. Multiparametric magnetic resonance imaging (mpMRI) provides high-quality data on PCa and is increasingly used in its diagnosis and surveillance, but computationally exploiting the wealth of data in these images to obtain precise information on tumour evolution to guide clinical management is an unresolved challenge. To address this timely issue, this project proposes to derive a personalised predictive mathematical model of PCa based on mpMRI to run organ-scale simulations that improve diagnosis and forecast the patient’s tumour evolution. The model will rely on robust biological and mechanical phenomena described via differential equations whose parameters are identified voxel-wise by solving an inverse problem using the patient’s clinical and mpMRI data at two dates. The model will then be validated by comparing simulation and actual data at a posterior date. The resulting predictive technology offers an unparalleled advance to personalise and optimise active surveillance for PCa, hence meeting many European Commission priorities for research in cancer. The candidate has previously developed computational models and methods to study PCa growth in clinical scenarios. Building on this ideal background, this project will provide him with crucial scientific techniques and skills to become a leading independent researcher, produce high-impact oral and written communications, and start an active network of collaborations between the US and Europe.

Mots clés : prostate cancer, active surveillance, multiparametric magnetic resonance images, computational oncology, patient specific, organ scale, isogeometric analysis, inverse problems, biomechanics

Participants :
- University of Pavia (Italie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 251002.56 €
- The University of Texas System (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet NANOCRISPR (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Prostate cancer is the second most common diagnosed malignancy and the fifth leading cause of cancer mortality in men. Whilst primary tumours respond well to therapy, tumours in the metastatic setting become inherently resistant to chemotherapy. Thus, more novel and effective therapeutic approaches are highly needed to treat this lethal disease. The cornerstone treatment for advanced prostate cancer consists of androgen deprivation therapy and docetaxel (DTX). However, both DTX activity and Androgen receptor (AR) signalling are highly interrelated. On the one hand, it has been shown that DTX is able to inhibit Androgen Receptor (AR) signalling and on the other hand, the activation of AR signaling can induce DTX insensitivity. In order to break this dependency of DTX effectiveness on AR signaling and ensure efficient treatment for advanced prostate cancer, we propose the selective inhibition of AR deploying CRISPR/Cas9 technology together with DTX. Both therapeutical approaches will be encapsulated into prostate-specific targeted nanoparticles which will allow the simultaneous delivery of the drug and CRISPR plasmids targeting AR into the tumour site. The designed state-of-art multi-functional nanoparticles will reprogram and sensitise the prostate tumour to DTX in situ, and will also induce a higher accumulation of the treatment in the tumour while healthy tissues will remain less affected. Moreover, the use of CRISPR/Cas9 will precisely engineer the prostate cancer cells to express lower levels of AR, contrasting with current anti-AR treatments, which have multiple off-targets. This approach represents an innovative targeted therapy for advanced prostate cancer. It will allow the administration of lower doses of chemotherapy with consequently reduced toxicity and the potential for longer tolerated treatment periods, whilst improving efficacy by selectively suppressing the molecular pathways causing cancer survival and resistance to treatment.


Participants :
- University of Castilla-La Mancha (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 172932.48 €
Projet HeriCare (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Protecting cultural heritage objects from biodeterioration and biodegradation is a major challenge faced by European society due to the implications in identity, economy and history. The aim of the HeriCare project is to create & expand a library of transparent hybrid materials composed of polyoxometalates & two-dimensional (2D) materials to be used in heritage conservation. This is the first time that such hybrids will be explored for this type of application and this project is expected to generate a broad impact on the fields of materials science and conservation. Moreover, selected hybrids will be incorporated to modern paper to provide ultra-resistant properties against biological contaminants for future heritage. The implementation of this multidisciplinary and multi-sectoral project is expected to boost the personal career of the candidate by completing his knowledge about chemistry synthesis and acquiring a whole new set of research skills related to microbiology, biochemistry and cultural heritage. Furthermore, a multidisciplinary network will be created via long research visits to the conservation department of the library of the Spanish Royal Botanic Gardens and a short visit to a Restoration School (Huesca, Spain), which are expected to provide a concise insight into conservation work and the state-of-the-art of cultural heritage preservation techniques and products. In return, the candidate will transfer his expertise on 2D materials to the hosting and the research visit groups, which is expected to open new research lines and future collaborations in the field of novel antimicrobial materials. Finally, the project management and additional activities such as courses, coaching and dissemination will provide key skills for financial management, communication, research development and mentoring, which will prepare the candidate for his career as a fully independent researcher and team leader.

Mots clés : 2d materials, polyoxometalates, biodeterioration, antimicrobial, restoration, conservation

Participants :
- Spanish National Research Council (Espagne) — Coordinator, beneficiary, Recherche, subvention : 160932.48 €
Projet QuantPalm_immunity (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - Global Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Protein fatty-acylations (N-myristoylation, S-palmitoylation and Lys-fatty acylation) are important lipid-modifications that regulate the trafficking and function of membrane-associated proteins in eukaryotes. With the development of new chemical proteomic methods by the Hang laboratory and others, many additional protein candidates of fatty-acylation have been reported. Notably, the Hang group has recently discovered several fatty-acylated proteins which are directly involved in host resistance to pathogens, such as IFITM3 and the autophagy factor Irgm1 (unpublished). Irgm1 is implicated in host clearance of intracellular pathogens by regulating autophagy in interferon-induced cells. These studies suggest a broader role for protein fatty-acylation in host immunity than previously appreciated. However, the functional analysis and quantification of many candidate fatty-acylated immunity-associated proteins remains to be determined. The objective of this research is to characterise and quantify S-palmitoylation of immunity-associated proteins and ultimately understand how dynamic fatty-acylation of these immune effectors contributes to host defence. Aim 1 involves the development of a quantitative chemical proteomic method for profiling S-palmitoylated proteins in naïve and stimulated immune cells. For Aim 2, I will analyse how S-palmitoylation affects the localisation and trafficking of autophagy factors (i.e. inducer of autophagy). For Aim 3, I will investigate how S-palmitoylation affects autophagy factors in host clearance of pathogens. These studies should provide important advances in understanding how protein S-palmitoylation influences autophagy-mediated clearance of pathogens and host resistance to intracellular pathogens, and therefore provide new opportunities to treat infections.

Mots clés : chemical biology, quantitative chemical proteomics, post translational modification, s palmitoylation, immunity, autophagy mediated clearance of pathogens, protein localisation, irgm

Participants :
- Rockefeller University (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- The Francis Crick Institute (Royaume-Uni) — Coordinator, beneficiary, Recherche, subvention : 251857.8 €
Projet RET-TRAF (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

Protein kinases play a critical role in a number of cellular processes, including cell proliferation, differentiation and apoptosis. The REarranged during Transfection (RET) receptor tyrosine kinase plays important roles in regulating cellular proliferation, migration, and survival in the normal development of neural crest derived tissues. Furthermore, aberrant activation of RET, through oncogenic mutations or overexpression, can contribute to tumourigenesis, regional invasion, and metastasis of several human cancers. RET relocalisation plays a role in cancer invasion and metastasis. Unfortunately, the detailed understanding of RET's dynamic function and the importance of quantitative, spatial and time-dependent parameters regarding RET trafficking is lacking. As such, the ability to manipulate RET activity using light would result in temporal control of enzymatic activity, thus serving as a valuable approach to probe the RET trafficking, further our understanding of cell movement and invasion. Cells will be exposed to photoresponsive RET inhibitors that can be turned on and off with light. Their effects on RET trafficking will be monitored by imaging. The results of these studies will provide new insights into intracellular RET trafficking and its role in cancer, ultimately leading to new therapeutic targets and improved disease management.

Mots clés : protein kinases, rearranged during transfection, oncogenic mutations, ret trafficking, photoresponsive ret inhibitors, therapeutic targets

Participants :
- University of Gothenburg (Suède) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 203852.16 €
Projet KMET-READ (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Protein methylation at lysine residues modulates chromatin structure, affects gene expression and mammalian development. Recently, it was also shown to influence the stability and activity of non-histone proteins. Lysine methylation marks manifest their biological effect via so-called ‘readers’ (or reading domains) which recognize and bind the methylation mark and directly alter the chromatin structure or act as a scaffold for other proteins, which induce biological responses. Reading domains include Plant homeodomains (PHD) and Chromodomains (CD) found in many chromatin proteins. KMET-READ plans to investigate the biological role of these reading domains in essential histone lysine methyltransferases - PHDs in MLL2 and MLL3 and CDs in SUV39H1 and SUV39H2. The results obtained here will advance the understanding of chromatin changes in human cells. The proposal will apply an interdisciplinary approach in an international environment to maximize its chances of success: the biological role of reading domains will be evaluated with molecular biology (histone and chromatin pulldowns, ChIP-seq, confocal microscopy), biochemistry (Peptide arrays, mass spectrometry, methyltransferase activity assays) and biophysics techniques (fluorescence anisotropy, circular dichroism spectroscopy) as well as crystallography (solving the structure of reading domains). Importantly, the KMET-READ project will also develop a yeast-3-hybrid method for the identification of new reading domains, which will allow to discover binding partners for just recently characterized new protein methylation marks. This novel method will be patented and introduced into market. All project partners will ensure an efficient dissemination and communication of the results of the KMET-READ project. The project will provide excellent training in research methods and other skills for the fellow that will strongly support her future career and initiate new and sustainable collaborations between the partners.

Mots clés : histone methylation, lysine methylation, methyllysine readers

Participants :
- University of Stuttgart (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 171460.8 €
Projet ProteinConjugates (Horizon 2020, appel à projets 2015)
Action : Doctoral Networks
Panel : Chemistry
Statut du projet : CLOSED

ProteinConjugates is an inter- and multi-disciplinary network for the education of talented young scientists who will learn how to rationally design and construct the next generation of chemically-defined and innovative protein drug-conjugates for the targeted treatment of serious conditions such as cancer or rheumatoid arthritis. A complementary interaction between academy and pharmaceutical industry is at the centre of such a network, which involves 8 academic groups and 1 SME partner as beneficiaries, and 2 leading European industrial partner organizations that will host secondments while providing training. The combined expertise of the beneficiaries and industrial partners in synthesis of complex molecules, molecular dynamics, supramolecular self-assembly, site-selective chemical protein modification, protein/antibody engineering, cancer therapeutics and drug development together with the experience in project management and training of PhDs and Postdocs of the PIs, will create a multidisciplinary environment where 10 young researchers can foster their knowledge and skills while developing the most innovative ideas in the emerging fields of chemical site-selective protein modification and protein biotherapeutics. Exposure to the highly dynamic and multidisciplinary ProteinConjugates environment will contribute to the education of the next generation of leaders in the emerging field of protein biotherapeutics, a key area of research and drug development for Europe's competitiveness.

Mots clés : aqueous reaction engineering, molecular dynamics, supramolecular self assembly, protein modification, antibodies, antibody drug conjugates, cancer therapy

Participants :
- University of Ulm (Allemagne) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 0.0 €
- PharmaMar (Spain) (Espagne) — Partner, organization partner, Organismes privés (hors enseignement), subvention : 0.0 €
- University of London (Royaume-Uni) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 273287.88 €
- Philochem (Switzerland) (Suisse) — Partner, beneficiary, Organismes privés (hors enseignement), subvention : 0.0 €
- Institut Curie (France) — Partner, beneficiary, Recherche, subvention : 262875.6 €
- University of Lisbon (Portugal) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 238356.36 €
- Hovione farmaciencia sa (Portugal) — Partner, organization partner, Organismes privés (hors enseignement), subvention : 0.0 €
- University of Vienna (Autriche) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 255934.08 €
- University of La Rioja (Espagne) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 247872.96 €
- Max Planck Society (Allemagne) — Partner, beneficiary, Recherche, subvention : 249216.48 €
- University of Cambridge (Royaume-Uni) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 273287.88 €
- University of Lisbon (Portugal) — Coordinator, beneficiary, Recherche, subvention : 741939.48 €
Projet MicroLightProtoCell (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Protocells are synthetic models of cells exhibiting rudimentary life-like properties, such as compartmentalization, sensing or replication, and constitute as such primitive forms of cellularity that could help to understand the origin of life. The remarkable properties of these smart micromachines can also be harnessed to tackle key societal challenges, including environmental clean-up, energy production, or drug delivery. Advances in this field would greatly benefit from the precise activation of protocells in both space and time. However, fine control over protocellular functions has been minimal to date. Conventional types of actuation (e.g. T, pH) do not allow spatiotemporal guidance due to their inherent inertia or the need to add chemicals. Light provides an attractive alternative for the remote manipulation of protocells with an extremely high spatiotemporal resolution. However, there is no precedent of light-actuated protocells in the literature. The aim of this proposal is precisely to design and construct a new class of photo-responsive protocells capable of being manipulated, activated or silenced quickly and locally in response to light. The bottom-up protocell assembly will be performed by microfluidics, whose powerful abilities in terms of modularity, reliability or sensitivity will be exploited to produce structurally well-defined architectures, and study interactions between protocells in a way unattainable with traditional methods. The expertise and skills of the applicant in the field of protocell design and light-responsive materials will be applied to the multidisciplinary and cutting-edge fields of microfluidics and synthetic biology in which the hosting groups at CNRS (under the leadership of Prof. Jean-Christophe Baret and Dr. Laurence Navailles) have made significant progress in the last few years.

Mots clés : protocell, microfluidics, photoresponsive system, synthetic biology, coacervate, self assembly

Participants :
- Centre national de la recherche scientifique (France) — Coordinator, beneficiary, Recherche, subvention : 173076.0 €
Projet HIPPOCRATE (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Proton therapy is rapidly being established in the EU as a promising external beam tumour therapy modality offering an increased tumour-dose conformity with better sparing of critical organs and healthy tissue compared to conventional photon therapy. However, full exploitation of its clinical potential is still hampered by non-negligible uncertainties during the treatment planning and delivery, posing the urgent demand of novel real-time techniques for in vivo verification of the proton beam range. To this aim, the objective of this project proposal HIPPOCRATE (Hybrid Imaging of PET and PrOmpt gamma for preCision RAnge- and biological- guidance in proton ThErapy) is to explore the optimal design and clinical potential of an innovative hybrid medical imaging approach that goes well beyond the state of the art, by combining real-time range verification from energetic prompt gammas with Positron-Emission-Tomography (PET) imaging of irradiation-induced or externally injected tracers, to promote biological- and dose- guidance for personalized, high-precision proton therapy. By improving the quality of the rapidly emerging proton therapy modality, this project will promote longer and healthier lives for cancer patients, with a high societal impact on the EU. Moreover, HIPPOCRATE can potentially go beyond the boundaries of medical imaging in proton therapy, by enabling high quality imaging of a whole new range of promising unconventional radionuclides for diagnostic nuclear medicine imaging, as well as opening the perspective of biological image guidance at the radiotherapy treatment site, independent of the primary radiation quality.

Mots clés : in vivo range verification, compton camera, radiation detectors, positron emission tomography, image reconstruction, image resolution, proton therapy, monte carlo simulations, medical imaging

Participants :
- Ludwig-Maximilians-Universität München (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 171460.8 €
Projet MONAGEL (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Pseudomonas aeruginosa (PA) is ubiquitous gram-negative bacteria. PA is a serious threat and is considered as a critical priority for treatment development by various institutions such as the World Health Organization. PA can cause infections on various location such as eyes, lung, skin (wounds). Immunocompromised patients are especially at risk, as PA is also able to colonize domestic and hospital fixtures. To add insult to injury, the infection is hard to treat and the number of antibiotic resistant PA is on the rise. The major challenge opposed by PA is its biofilm. Biofilms are a structured bacterial community embedded in a matrix composed of exopolysaccharides, proteins, extracellular DNA, and lipids. PA present in the biofilm are a thousand times less sensitive to antibiotics than their planktonic form. The MONAGEL project propose to fight the PA in the biofilm by developing a hydrogel made of cross-linked lipid nanoparticles. The lipophilic core of the lipid nanoparticles will be used to encapsulate hydrophobic active ingredients, the aqueous cavities of the gel will be used to encapsulate hydrophilic ones. The hydrophobic and hydrophilic compartment will enable work with a broad variety of molecules such as fluorescent probes (which will permit a thorough characterisation of the gel) or active ingredients such as antibiotics and pathoblockers. The latter molecule will be efficient to design the gel towards fighting PA biofilm either by inhibiting quorum sensing (bacterial communication) or lectin interaction (key role in biofilm formation). Well thought work and contingency plans have been put in place to ensure the success of MONAGEL development. The innocuity of the system will be assessed on various cell lines, and the antibiofilm efficacy will be tested on in vitro models. In the end, the MONAGEL efficacy will be demonstrated on a co-culture model (epithelium + biofilm) as a proof-of-concept to serve as a selling point for further development.

Mots clés : hydrogel, nanomedicine

Participants :
- Helmholtz Centre for Infection Research (Allemagne) — Coordinator, beneficiary, Recherche, subvention : 174806.4 €