Data-Gouv-ML/pcri-actions-marie-curie-participations-et-projets-laureats huggingface dataset:
Projet JTIM (Horizon 2020, appel à projets 2016)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Block copolymer (BCP) self-assembly in solution has attracted considerable attention for many decades because it can yield ordered nanoscopic core-shell structures (micelles) with a wide range of morphologies. These aggregates offer potential applications in many fields, and cylinders are among the most promising for uses in nanomedicine (e.g. as drug delivery vehicles). In this proposal, state-of-the-art strategies to access well-defined micelles with tailored structures will be applied to the preparation of biodegradable monodisperse cylindrical micelles and block comicelles in water. Once formed, the micelles and their hierarchical assemblies will be characterized in detail and explored in potential nanomedical applications. To achieve these objectives Dr. Jia Tian, an exceptionally talented young scientist from China who performed his Ph.D. in a top supramolecular chemistry group in China (Zhan-Ting Li, Fudan University), will work in the internationally leading polymer and materials research group of Prof. Ian Manners (Bristol, UK) where he will learn polymer synthesis and state-of-the-art self-assembly techniques and will obtain a broad background in polymer and BCP synthesis, self-assembly, and polymer materials science. Armed with the new knowledge and experience gained, following the fellowship Dr. Tian aims to obtain an academic position in China where soft materials such as biodegradable BCPs and their applications in nanomedicine will play a key role.

Mots clés : crystallization driven self assembly

Participants :
- University of Bristol (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 195454.8 €
Projet DYNAMIN (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Bone is a complex nanocomposite with outstanding mechanical properties arising from the nanoscale interaction between its two main building blocks: type I collagen fibrils and hydroxyapatite crystals. Despite its clinical relevance, the mechanisms governing bone formation are still poorly understood, mainly due to the complexity of the processes. During bone formation and remodeling, non-collagenous proteins and proteoglycans act synergistically to regulate the mineral deposition process, participating in multiple signaling pathways involving regulatory molecules, osteoblasts and osteoclasts. Many of the studies performed until now relayed into simplified in vitro models that hardly represent this complexity. Furthermore, methods traditionally applied only provide snapshots of this process, unable to extract dynamic information. To really understand the mechanisms regulating bone mineralization, we need to simultaneously visualize its different components in its context, to be able to monitor their interactions. In this project, I propose to combining liquid-phase electron microscopy and immunolabelling, with which I aim to bring together dynamic imaging of a complex biochemical process and the identification of the biomacromolecules involved. By recreating the mineralization conditions inside the liquid cell, I aim to obtain real time data on nucleation sites, crystal growth and mineralization dynamics. The combination of dynamic imaging with immunogold will allow me to monitor the direct interaction of these regulatory molecules with the mineral particles at nanoscale resolution. By means of this new exciting approach I expect to provide unprecedented data on the processes of bone formation and take a step forward in the application of LPEM in biological materials.

Mots clés : biomineralization, liquid phase electron microscopy, collagen mineralization, apatite, bone, in situ electron microscopy, proteoglycans

Participants :
- Radboud University Nijmegen Medical Centre (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 187572.48 €
Projet PBH MUSE (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

Born in the first moments of the universe, primordial black holes (PBHs) could provide the answers to many of the biggest open questions in cosmology. How did the universe begin? What is dark matter made of? PBHs are one of the oldest candidates to explain the nature of dark matter (DM), and considered by many to be one of the leading candidates — DM may be nothing more than swarms of PBHs clustered in haloes around every galaxy, and even if PBHs only make up a sub-dominant component of DM, their possible existence still has great implications not only for the evolution of the Universe, but also its creation. It is the aim of this project to improve constraints on the primordial universe, and to determine the origin of the black holes observed by LIGO-Virgo. To achieve this, I will perform studies fitting into 3 broad categories. Firstly, the formation of PBHs and binary systems in the early universe will be studied. The results will be used to determine an appropriate window function for use when calculating the PBH abundance - eliminating the largest source of uncertainty when calculating constraints on the primordial power spectrum from PBH constraints. Secondly, small-scale simulations will be used to determine the effect of PBHs on structure formation, which will be important for determining how external forces/objects might affect the evolution of binary PBH systems. Potentially, this may also lead to observable differences in the substructure of dark matter haloes between models with and without PBHs. Finally, the formation, evolution and possible disruption of systems containing 2 (or more) PBHs (or other compact objects) will be studied, making use of results from the previous sections.

Mots clés : primordial black holes, cosmological perturbation theory, early universe

Participants :
- Leiden University (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 187572.48 €
Projet PhoQuS-G (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : CLOSED

Bose-Einstein condensates (BECs) are extremely cold Bose gases consisting of a large number of interacting atoms. BECs have quantum properties that can be exploited perfectly for high precision metrology. The goal of the research project Phononic Quantum Sensors for Gravity (PhoQuS-G) is an extensive analytical and numerical analysis of the use of phonons (quasi-particles of phase and density perturbations) in BECs for high precision sensing of gravitational fields. The project will be built upon a powerful numerical method employed by the host group that enables the description of condensate splitting, trap release and other (strong) changes of the BEC. This method will be combined with an elaborate description of cold Bose gases, incorporating effects of quantum noise and finite temperature and providing access to second order correlation functions of the Bose gas. The numerical approach will enable the analysis of the most promising parameter regimes and provide a description of the full time-evolution of BECs, including probe state preparation and measurement. Measurement precision will be optimized using methods of quantum metrology. A clear pathway will be given towards first gravimetry experiments with phonons in BECs. Such experiments can lead to the development of phononic quantum sensors, a very promising quantum technology. High precision sensing of gravitational fields offers a variety of applications - from fundamental research to technological solutions; for example, knowledge about local gravitational fields (geodesy) can be used to map underground infrastructures, find natural resources or ease navigation. As BECs exist on the micrometer scale, precise measurements of gravitational fields on short distances and of very small objects can be implemented far beyond the scales explored to date. This may offer opportunities for new exciting experiments investigating the interface of quantum mechanics and gravity.

Mots clés : gravity, gravimetry, bose einstein condensates, phonons, numerical methods, interacting bose gas, quantum metrology, many body quantum systems, quantum optomechanics

Participants :
- Humboldt-Universität zu Berlin (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 162806.4 €
Projet THERMUCNA (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Bovine mastitis (BM) is the most prevalent disease that affects dairy cows in many countries and it is the most important cause of economic losses in the dairy industry worldwide. The dairy activity is very important for the European economy, producing nearly a quarter of the world’s available milk. Currently, BM control consists mainly of antibiotic therapies. However, they usually cannot eradicate the infection due to acquired drug resistance and survival strategies of bacteria. The mechanisms developed by pathogens are intracellular and biofilm lifestyles that allow them to persist in the mammary gland protected from antibiotic therapies and host immune response. So new therapeutic approaches are needed. The present research project proposes the employment of smart nanogels (NGs) for antimicrobial delivery into mammary gland for BM treatment. The synthesized NGs will present: (i) nanometer size; (ii)thermoresponsive behavior: thermally triggered drug release; (iii) disulfides in their structure: mucoadhesive trigger upon the mucosal environment; (iv) modulated positive charge which will improve their penetration into bacteria biofilms. Several polymers and crosslinker agents will be evaluated to obtain a series of NGs. Defensin 5 and ceftiofur will be studied as antimicrobial agents to entrap into NGs. The virulence mechanisms developed by bacteria are the main responsible for the failure of antimicrobial treatments. Therefore, NGs will be studied and characterized to find suitable nanocarriers with the ability to penetrate bacterial biofilms and internalize host cells, blocking the virulence mechanisms developed by pathogens. Also, the smart drug release lets ensure that the exposition of the host to antimicrobial will be minimum and necessary to kill bacteria. This fact contributes to reducing bacterial resistance development. Nanotechnology in BM treatment is poorly explored which highlight the novelty of the research project proposed.

Mots clés : thermoresponsive nanogels, mucoadhesive nanogels, biofilm penetrating, nanogels, intracellular drug delivery

Participants :
- University of the Basque Country (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 172932.48 €
Projet Brain Metastases (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Brain metastases, particularly from breast cancer, are a significant clinical problem. About one fifth of breast cancer patients that develop metastatic disease will experience brain metastases. Survival is extremely poor, with a median survival of approximately three months. One of the main issues with treating brain metastases is the late stage at which the majority of brain metastases are diagnosed and the ineffectiveness of available therapies as a consequence. At this late point, it is often too late for standard therapies to have a meaningful effect on the progression of the tumours. In recent years, the role of the immune system in the progression of systemic metastases has been described, with circulating monocytes being found to play a significant role. However, little is known about the pathogenesis of metastases within the brain. The brain possesses a very different environment to the rest of the body, with the blood brain barrier (BBB) tightly regulating the movement of nutrients, drugs and cells into the brain. Consequently, the processes that modeluate metastasis progression in other organs, such as lung and liver, may not be reflected within the brain owing to its unique environment. The overall goal of this fellowship, therefore, will be to determine the role of circulating monocytes in the development of brain metastases from breast cancer with the aim of identifying potential therapeutic routes. We believe that circulating monocytes may play a significant role in the development and progression of brain metastases as a separate, distinct population from the resident macrophage population (microglia) within the brain. We hypothesize that there is significant circulating monocyte infiltration into brain metastases, which is associated with increased BBB breakdown and disease progression. On this basis, we propose that inhibiting these circulating monocytes will significantly reduce both initiation and progression of brain metastasis.

Mots clés : cancer, brain metastasis, metastasis, macrophages, monocytes, circulating monocytes, magnetic resonance imaging, gadolinium

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

Breast cancer (BC) represents a leading cause of cancer-related death in women worldwide, in large part due to ineffective detection and treatment. Nanotechnology offers new promise in mitigating BC mortality, by combining therapy with early diagnosis in “theranostic” nanoparticles (NPs). Here, a multidisciplinary approach is proposed to develop and evaluate novel theranostic NPs, which for the first time combine near infrared (NIR) metal-enhanced fluorescence (MEF) imaging with multimodal cancer treatment. MEF is a promising strategy for dramatically improving the low fluorescent signals of available NIR dyes, but limited MEF platforms for in vivo applications have been developed. Here, elongated gold (Au) NPs (nanobipyramids) with two sharp tips and tunable sizes/optical properties are expected to provide distinct advantages, including large fluorescence enhancement and increased tumour accumulation, thus enabling real-time in vivo imaging with high sensitivity and spatial resolution. Furthermore, BC photothermal therapy by the Au core will be combined with a chemotherapeutic drug-carrier surface coating, bearing pH-responsive lids to allow controlled drug and Zn ion release at the tumour site. Coordinated use of these modalities is expected to minimize systemic side effects, improve therapeutic efficacy and be useful in treating drug resistant tumours. Several complementary techniques, including computational modelling, 3D in vitro cell cultures, in vivo testing and advanced 3D imaging will be combined to characterize NP biodistribution, biocompatibility and passive vs. active tumour targeting. These will provide vital insights for the – still challenging – clinical translation of NPs in general, paving the way toward personalized nanomedicine. The proposed research/training will complement the Applicant’s skills in materials science with the Host’s expertise in cancer drug delivery to enhance his professional maturity and promote international collaborations.

Mots clés : metal enhanced fluorescence imaging, multifunctional nanoparticles, nanobipyramids, hyperthermia, controlled drug release, breast cancer models

Participants :
- University of Cyprus (Chypre) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 151648.8 €
Projet MTOAC (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Breast cancer is one of the most common causes of cancer-related death in women all over the world. Although therapeutic approach like surgery, chemotherapy, radiation and targeted therapy reduced the risk of cancer specific mortality. Still there is a risk of cancer recurrence and mortality. Cancer research is typically dependent on 2D system and animal model which leads to conflicting the result due to cellular behavior, phenotypes, gene expression level and expensive animal studies (Szot et al., 2011). In this way 3D microfluidics systems are designed to fulfill the gap between 2D and animal model for screening and testing of drug. The present proposal is conceptualize to bridge the gap between 2D and animal model effectively, by designing the Organs-on-chip (3D), microfluidics system of tumor microenvironment to evaluate the efficacy of combination of anticancerous drug. Herein, the multi-compartment microfluidics platform will be generated by co-culturing of cancer cells, fibroblast and endothelial cells into biocompatible hydrogel, to produce a multi-organ-on-a-chip devices. It recapitulates organ-like functions in each compartment and a vascular-channel between the compartments produce preliminary human on-chip. This 3D microfluidics system dedicated to evaluate the efficacy of anticancerous drug will be helpful to improve the future drug development applications.

Mots clés : microfluidics, tumor on a chip, biomaterials, in vitro 3d models, pharmaceutical testing

Participants :
- Elvesys (France) — Coordinator, beneficiary, Organismes privés (hors enseignement), subvention : 185076.0 €
Projet BRIDGES (Horizon 2020, appel à projets 2014)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Breast cancer is the most common cancer among European women showing high clinical and molecular heterogeneity. Current clinical management causes patients overtreatment with implications on both patients’ quality of life and healthcare costs. Moreover, intrinsic or acquired tumor resistance to treatment leads to incurable metastatic progression in a significant proportion of patients. Advances in cancer genomics highlighted a high inter- and intra-tumor genetic heterogeneity, reinforcing the need for a mutation-based personalized treatment and a way to non-invasively monitor evolving disease. This project will significantly contribute in addressing such unmet challenge aiming 1) to identify altered breast cancer driver pathways, 2) to study their association with drug response and 3) to develop tools for a non-invasive assessment of such alterations. By integrating multi-dimensional molecular data from more than 3000 cases, driver pathways will be identified and their association with previous breast cancer classifications as well as their prognostic significance will be studied. Their predictive power will be investigated in a matchless bio-bank of Patient Derived Xenografts, a much more reliable pre-clinical model, able to recapitulate inter- and intra-tumor heterogeneity observed in patients. Multi-dimensional molecular data and high throughput drug screenings are available and will be integrated to identify novel pharmacogenomics associations. Mining of such amount of data will allow defining a portfolio of relevant breast cancer alterations that will be sought in plasma of patients from the DETECT trial, towards a non-invasive monitoring able to guide therapeutic strategy. Development and application of cutting-edge computational approaches is fundamental to reach above aims and it will constitute a major part of the efforts, considerably expanding Experienced Researcher's know-how in the field of cancer genomics and translational medicine.

Mots clés : breast cancer, next generation sequencing, cancer genomics, cancer biomarkers, precision medicine, circulating tumor dna, drug resistance

Participants :
- University of Cambridge (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €
Projet P70-IMMUNEBREAST (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Breast cancer is the most common cancer among women with significant death rates and economic impact. In daily routine clinics, breast cancer is usually classified on the basis of three immunohistochemical markers (ER, PR and HER2). Triple-negative breast cancer (TNBC) is a subtype defined by the negativity of all these markers, which shows an adverse clinical course. It is characterized by a considerable gene expression heterogeneity that leads to a lack of availability of targeted therapies. Positive clinical trials relying on various forms of immunotherapy have shifted the paradigm of diverse malignancies from cytotoxics to novel immunomodulator drugs. The results in TNBC, however, are not as positive. In a recent taxonomic effort of the hosting group, TNBC has been re-classified on the basis of the activation status of six protein kinases, which in turn constituted novel targets for this disease. One of them, the 70-kDa ribosomal protein S6 kinase (P70S6K), which was associated with an adverse clinical outcome, showed negative correlation with tumor-infiltrating lymphocytes (TILs) abundance. The fact that P70S6K has been associated with immunosuppressive mechanisms and that there is a positive correlation between the number of TILs and the clinical outcomes in TNBC, suggests that the role of P70S6K may be related to pleiotropic and/or opposing properties of tumor progression. By using a combination of multiparametric flow cytometry, bulk/single-cell gene expression analysis and in vivo experiments in mouse models, this proposal aims to unravel the impact of P70S6K modulation over the already known relevant immune-oncology targets/axes as well as the therapeutic consequences of P70S6K blockade in TNBC. These studies will provide a better understanding of the lymphocyte-related responses modulated by P70S6K, with the potential to find new therapies for patients suffering from TNBC and possibly a broader range of malignances.

Mots clés : p70s6k, breast cancer, tils, immunotherapy, tnbc

Participants :
- Spanish National Cancer Research Centre (Espagne) — Coordinator, beneficiary, Recherche, subvention : 160932.48 €