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

Cancer is the second leading cause of death globally. Noninvasive imaging of tumor hallmarks helps to combat cancer more efficiently. However, cancer is a complex disease and modern imaging of cancer should evolve to help exploring the interaction between different cancer hallmarks and to predict the evolution of some of them in relation to others. Besides, these new techniques should provide answers to the present unmet need for determining, precisely, how, which and when targeted therapeutic agents can be used for optimized efficacy. In this project we will build a new hybrid cancer imaging device: OCTOPUS (Oncological Concurrent Tomographic Optoacoustics, PET and UltraSonography), that will pioneer the intersection of molecular, vascular and tissue oxygenation information, three major hallmarks of cancer. OCTOPUS is a timely action to study tumor dynamics with a hybrid hallmark perspective in a longitudinal, simultaneous, quantitative, fully co-registered and in vivo manner. To reach this goal, I will develop cutting-edges technologies regarding multispectral tomographic optoacoustic using an arrangement of 3D ultrasound arrays, combined with actual 3D sequences of Ultrafast Ultrasound and a custom-made PET system for data acquisition and reconstruction. A deep learning framework will be created for advanced multiparametric analysis of OCTOPUS derived data to facilitate the interpretation of intra-tumoral processes in order to improve high-precision image-guided treatment and ultimately to guide in the design of targeted therapies.

Mots clés : hybrid imaging, imaging for oncology, ultrafast ultrasound, optoacoustics

Participants :
- Universidad Complutense de Madrid (Espagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 160932.48 €
Projet Tex-Mex (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cancer is the second leading cause of death in the European Union, having killed 1.4 million people in 2018 alone. Chimeric antigen receptor (CAR) T cell therapy is a ground-breaking cancer treatment that has demonstrated striking results in fighting blood cancers. However, T cell exhaustion, a process that results in the progressive development of lymphocyte dysfunction due to prolonged antigen stimulation in cancer, chronic inflammation or infection, has been a major obstacle in translating CAR T cell therapy to solid tumours. The solid tumour microenvironment is biomechanically distinct from physiological conditions, being characterized by higher interstitial pressures, higher stiffness and a distinctive vascular architecture. While biochemical triggers for T cell exhaustion have been well characterized, biomechanical influences are understudied. This project seeks to (i) use a microfluidic model to add the biomechanical dimension to our current understanding of the development of T cell exhaustion and (ii) use synthetic biological approaches to engineer “biomechanosensor-actuator devices”. These will be intracellular systems based on synthetic biological circuits that will integrate biochemical and biomechanical cues of T cell exhaustion and trigger genetic pathways to counteract the development of dysfunctional phenotypes. Integrating the biomechanical and biochemical dimensions will yield a more sophisticated cell therapy platform to neutralize T cell exhaustion. Ultimately this would provide a safer, more effective and universal treatment for cancer by preventing T cell exhaustion and immune escape.

Mots clés : synthetic biology, t cell exhaustion, biomechanics, microfluidics, 3d scaffolds, tumour architecture

Participants :
- Italian Institute of Technology (Italie) — Coordinator, beneficiary, Recherche, subvention : 171473.28 €
Projet RNADIAGON (Horizon 2020, appel à projets 2018)
Action : Staff Exchanges
Panel : Life Sciences
Statut du projet : SIGNED

Cancer occurs in more than 2 million individuals every year in Europe alone. It is widely recognized that early diagnosis and monitoring of the disease - during therapy and post-treatment follow-up- is a key step for successful patient management: it helps to offer on-time curative intervention and selecting the most appropriate therapy, improves the quality of life, while contributing to reduce the economic and social burden for both patients and society. There are screening programs available for early detection of some cancers such as colorectal cancer (CRC). Unfortunately, current CRC screening tests suffer with unsatisfactory sensitivity and specificity and low compliance of targeted population. On the other hand, there are cancers with poorly performing biomarkers as in the case of hepatocellular carcinoma (HCC), or no biomarkers at all (e.g. renal cell carcinoma (RCC), which limits not only the screening options but also the diagnosis or monitoring of the disease. Therefore, there is a need for new diagnostic biomarkers and accurate technologies to enable precise detection of asymptomatic tumors in a short time, low costs and, if possible, with minimal invasiveness and risks for the patients. From this perspective, cancer specific small non-coding RNAs (small ncRNAs) circulating in body fluids such as blood serum or plasma present promising diagnostic approach. Project RNADIAGON aims at development of personal skills and knowledge of early-stage and experienced researchers working in the field of small non-coding RNA diagnostics from five European research institutions through their long-term stays at one of the world-leading ncRNAs research centers in United States and traineeships at the education center and manufacturing facilities of industrial partner developing small ncRNAs-based certified diagnostics. This research and innovation staff exchange will increase the scientific excellence and quality of related research in the EU research institutions.

Mots clés : small non coding rna, microrna, piwi interacting rna, diagnostic, colorectal cancer, renal cell carcinoma, hepatocellular carcinoma, biomarker

Participants :
- Iuliu Hațieganu University of Medicine and Pharmacy (Roumanie) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 124200.0 €
- BioVendor (Czechia) (Rép. Tchèque) — Partner, beneficiary, Organismes privés (hors enseignement), subvention : 82800.0 €
- University of Ferrara (Italie) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 96600.0 €
- Universität Hamburg (Allemagne) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 96600.0 €
- Masaryk University (Rép. Tchèque) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 165600.0 €
- The University of Texas System (Etats-Unis) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Medical University of Graz (Autriche) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 96600.0 €
Projet ClickandTreatCancer (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Cancer remains one of the leading causes of mortality worldwide. Prostate cancer (PC) is currently the most common male malignancy and remains the leading cause of death. Despite advances in chemotherapy, current strategies still carry severe side effects and offer limited benefit to the patient. Two main reasons behind these limitations include 1) non-specific delivery of anticancer drug to the target tissue and 2) poor diagnosis at an early stage of the disease. Thus, there is an urgent need for a novel and modular theranostic platform to deliver drugs selectively to cancer tissues and simultaneously follow therapeutic efficacy through non-invasive imaging techniques. Herein we propose a DT-diaphorase activated, DUPA guided NIR-based theranostic strategy to deliver anticancer drug selectively to prostate cancer cells while monitoring in real-time drug release and efficacy in vivo. The developing tool is novel and modular, enabling the use of various triggers, drugs and targeting agents. The fluorophore signal is expected to fall in the NIR region (>600 nm) and the scaffold with enable as real-time monitoring of drug release in vivo, as well as the introduction of targeting groups in order to improve the specificity of the theranostic agents towards cancer cells. The development of this technology can provide an invaluable platform that can be easily adapted for the treatment of different cancer types. It is likely that the directness and modularity of this novel approach will have a strong impact in the field of targeted drug-delivery for treating and monitoring in real-time drug effectiveness.

Mots clés : theranostic prodrugs, targeted therapeutics, nir probe, prostate cancer, pmsa, dupa, dt diaphorase

Participants :
- University of Lisbon (Portugal) — Coordinator, beneficiary, Recherche, subvention : 159815.04 €
Projet ABPP-PROTDRUG (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : SIGNED

Cancer remains one of the most prevalent diseases worldwide and new therapeutic targets are highly sought. The oncogenic triangle LIN28/HMGA2/IGF2BP1 is a self-promoting pro-tumorigenic group of proteins with relevant roles in many cancers that antagonize the let-7 family of miRNAs, which possess anti-tumorigenic roles. Activity-based protein profiling applied to the measurement of cysteine reactivity profiles has been efficiently used to profile the landscape of ligandable cysteines in a given phenotype, which in turn has allowed the discovery of novel therapeutic targets in relevant disease phenotypes and the pharmacological modulation of targets previously described as undruggable. Our approach will characterize the influence of the LIN28/HMGA2/IGF2BP1 proteins in the cellular landscape of ligandable cysteines, focusing on liver and ovarian cancer. Additional protein interacting partners to the oncogenic triangle will be identified and validated as novel anti-tumor targets. Variations in the probes used will allow the established methodology to be adapted to other entities like serine hydrolases, well known players in cancer and metastasis, or sulfenic acids, oxidized cysteines known to take part in redox control of the cellular environment. Cysteine labeling chemistries and protein engineering will be used to weaponize LIN28/HMGA2/IGF2BP1 and their protein interactors against the oncogenic triangle as “protein drugs” via proximity-enabled reactive therapeutics, where reactive aminoacids are introduced in a native protein structure to allow a transient non-covalent interaction to be stabilized by formation of a permanent covalent bond. This approach is at the frontline of novel therapeutic methodologies and its application will restore the levels and function of let-7 miRNAs and their anti-tumor properties. The outcome of this project will establish a powerful platform to weaponize transient non-covalent interactions as innovative therapeutic modulators.

Mots clés : activity based protein profiling, protein engineering, protein drugs, cancer, mirna

Participants :
- University of Cambridge (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €
Projet MIC (Horizon 2020, appel à projets 2020)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Physics
Statut du projet : SIGNED

Cancer remains the second leading cause of death worldwide (World Health Organization), involving various pathological processes across multiple biological scales . Ultrasound is increasingly used in clinical oncological practice for patient diagnosis, therapy guidance, and monitoring, however do not allow for imaging of the metabolic and vascular onset of cancer at the microscale . Here, I aim to develop multi-messenger ultrasound imaging for the early metabolic and vascular detection of cancer in a pre-clinical model and a pilot human head and neck oncology study. This interdisciplinary proposal will build on three recent breakthroughs in ultrasound and synthetic biology: (1) 4D ultrasound imaging at the millisecond timescale, (2) ultrasound super-resolution imaging at the microvascular scale and (3) biomolecular ultrasound imaging at the cellular scale.I will develop non-linear sound sheet imaging (NSSI) for the 3D imaging of ultrasound contrast agents regardless of their motion. Combined with localization algorithms, this method will enable 3D ultrasound microscopy (SSLM) of capillary networks perfused with clinically approved contrast agents. Using this vascular message we will characterize rat brain tumors in preclinical research. We will also evaluate the potential of the ultrasound microscopy technique to detect metastatic sentinel lymph nodes in a pilot human study. Furthermore, NSSI will be capable of imaging GVs that are small enough to extravasate the leaky vasculature of tumors. In this specific aim, I will rely on genetically engineered pH-sensing GVs developed in my host laboratory (NWO Start-up Grant STU.019.021 of the Dutch Research Council). Using this metabolic message we will detect hypoxia induced acidosis, an important biomarker of cancer. The non-invasive observation of structural and metabolic messages arising from tumors with sound, named multi-messenger ultrasound imaging of cancer (MIC), will significantly advance the potential of medica

Mots clés : super resolution, microscopy, biomolecular ultrasound

Participants :
- Delft University of Technology (Pays-Bas) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 175572.48 €
Projet CApaCITy (Horizon 2020, appel à projets 2018)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cancer stem cells (CSC) initiate, sustain the prevalence, and resistance to therapy of skin squamous cell carcinomas (SCC). It is well acknowledged that CSC self-renewal and clonal growth is governed by genetic mutations, but also by complex interactions between CSC and the microenvironment. Genetic therapy is difficult to achieve in clinical settings, therefore, targeting cells of the supportive tumor microenvironment is a promising advance to eradicate SCC. Using mouse models of SCC, our previous basic research results uncovered the existence of a direct crosstalk between skin CSC and tumor-associated macrophages (TAM) via Wnt signaling. Interestingly, we observed that Wnt regulated the expression of three CSC receptors, CD99, MFGE8 and Nectin-2, and governed the CSC-TAM crosstalk. Here, I propose to expand this basic research into a translational perspective, to explore the potential of CD99, MFGE8 and Nectin-2 as therapeutic targets for human SCC. There is a major interest in this arena, since the major caveat of targeting Wnt signaling in cancer is the lack of specificity to target CSC, without affecting somatic cells. Moreover, most clinical trials have not been fully efficient to dampen the Wnt response in tumors. Using a comprehensive and integrated approach based on human SCC, cell biology, omics and medical chemistry, along with powerful patient derived xerographs (PDX), my results must likely unearth a role for these immunoreceptors in governing the CSC-TAM crosstalk, and their potential as drug targets for human SSC. This interdisciplinary project will be conducted at the University of Copenhagen (UCPH) in Dr. Perez-Moreno, Dr. Merete Haedersdal, and Dr. Strømgaard groups. Through the CApaCITy project, I will embark in a leading research area with several possibilities to grow into an independent international researcher.

Mots clés : squamous cell carcinoma, cell cell interaction, cancer stem cells, macrophages, immunoreceptors

Participants :
- University of Copenhagen (Danemark) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 207312.0 €
Projet PROMIGREX (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Life Sciences
Statut du projet : CLOSED

Cancers arise in cell types that turnover by proliferation and death at highest rates, likely because these rates become unbalanced. Our group found that mechanical forces control both processes in epithelia: stretch activates proliferation whereas crowding activates cell extrusion and death. However, it was unclear what causes crowding and stretching forces in epithelia. I will investigate if cell migration from sites of proliferation drives the conveyor belt forces that control stretch-induced cell division and crowding-induced death. If so, the rate of cell migration could drive the rate of cell turnover and, hence, the propensity for a tissue to become cancerous. While my host lab has already identified roles for the stretch- activated ion channel Piezo1 in controlling proliferation and extrusion, based on preliminary compelling findings, I will determine if it also controls cell migration from sites of division. To do so, I will use established models in cell culture and mouse gut and develop an in vivo zebrafish gut model for homeostatic epithelial cell turnover. Additionally, I will test if frequent Piezo1 mutations in colon cancer impact cell proliferation, migration, and death. If my hypothesis is correct, I will reveal a new, unexpected role for cell migration in not only normal epithelial cell turnover but also in carcinogenesis. Should Piezo1 act as a central transducer of mechano-chemical coupling, it could provide a new target for therapeutics.

Mots clés : calcium, mechanics, piezo1, mdck, zebrafish, migration, division, polarity, extrusion

Participants :
- University of London (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 212933.76 €
Projet CANLEISH (Horizon 2020, appel à projets 2020)
Action : Staff Exchanges
Panel : Information Science and Engineering
Statut du projet : SIGNED

Canine leishmaniasis is among the most important vector-borne parasitic diseases of dogs. This study will focus on investigating the feasibility of a non-invasive methodology for the diagnosis of canine leishmaniasis in dogs via the analysis of non-invasive volatile samples emitted by dogs’ breath and hair, employing analytical methods and a system composed of different chemical gas sensing devices.

Mots clés : canine leishmaniasis, diagnosis, volatile organic compounds, biomarkers, gc ms, nanomaterials, chemical gas sensors  electronic nose

Participants :
- University of Pamplona (Colombie) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- Institut Pasteur de Tunis (Tunisie) — Partner, beneficiary, Recherche, subvention : 565800.0 €
- Université Moulay Ismail de Meknes (Maroc) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
- N vision systems and technologies sl (Espagne) — Partner, beneficiary, Organismes privés (hors enseignement), subvention : 174800.0 €
- Spiru Haret University (Roumanie) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 446200.0 €
- Electronic nose company limited (Thaïlande) — Partner, organization partner, Organismes privés (hors enseignement), subvention : 0.0 €
- Estonian University of Life Sciences (Estonie) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 363400.0 €
- Uppsala University (Suède) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 331200.0 €
- Universite d'el tarf (Algérie) — Partner, organization partner, Enseignement supérieur ou secondaire, subvention : 0.0 €
Projet PHOTOCARBOX (Horizon 2020, appel à projets 2019)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Carbon dioxide is released into the atmosphere at an ever-increasing rate due to the burning of fossil fuels. At the same time, the production of bulk and fine chemistry mostly relies on the same crude oil as a carbon source. This situation is unsustainable and therefore calls for the recycling of CO2 as a carbon source. State-of-the-art methods are not sufficient to balance the carbon cycle and therefore it is important to increase the scope of available reactions using CO2. In this proposal, we aim to develop a new methodology using CO2 as a C1-synthon to open up new synthetic pathways. We will bind CO2 to a metal centre and use a radical-coupling pathway to form C-C bonds through an atom-efficient transformation. In this way, we aim to synthesise both natural and unnatural chiral amino acids from amines using visible light and combined photoredox- and CO2-catalysis. The project will contribute to uphold Europe as a world-leader in sustainability by developing novel green methodologies, as well as maintain it as a respected destination for outstanding research by dissemination of the results to both experts and a broader audience. Furthermore, the highly interdisciplinary project and extensive training will prepare the researcher to pursue a successful career in sustainable chemistry.

Mots clés : amino acids, carbon dioxide, light, catalysis, photo, valorisation, green chemistry, carboxylic acid, radical coupling

Participants :
- Institut Català d'Investigació Química (Espagne) — Coordinator, beneficiary, Recherche, subvention : 160932.48 €
Projet NIRCOThera (Horizon 2020, appel à projets 2017)
Action : Postdoctoral Fellowships - European Fellowships
Panel : Chemistry
Statut du projet : CLOSED

Carbon monoxide (CO) is a gaseous signaling molecule naturally produced by the human body. In recent years, CO has shown its anti-inflammatory and immunomodulatory properties and thus therapeutic potential in the treatment of inflammatory disorders and cardiovascular diseases. It is promising to exploit the modulatory effect of exogeneous CO in tumour microenvironment where inflammation and angiogenesis are the critical components of tumour progression and metastasis, which is largely unexploited. For this purpose, it is key to manipulate CO exposure in a precise dose and time-controlled manner exclusively at the tumour site. Herein, we propose to develop a new CO delivery avenue, enabling controlled CO release to tumour sites with spatiotemporal precision by using near infrared light (NIR). Specifically, the strategy consists of single-walled carbon nanotubes (SWCNTs) loaded with CO releasing molecules (CORMs). We have reported the development of a SWCNTs-based bifunctional system that enables intratumoural protein delivery and NIR activation, which is ready to be applied to realize controlled CO release in vivo. We plan to conjugate [ReBr3(CO)3][NEt4]2 to SWCNTs. The rhenium complex is chosen because of its stability and non-toxicity while the lipid functionalized SWCNTs have shown biocompatibility, ultrahigh tumour uptake and relatively fast clearance and excretion from the health tissues, which impart the platform promising for in vivo application. We will evaluate the stability of the platform, followed by the NIR-triggered CO release profile and then dose- and time-dependent effect on both cancer cells and tumour-infiltrating immune cells, including the generation of reactive oxygen species (ROS) and expression of multiple genes associated with tumour progress. Furthermore, expecting increased cancer cell sensitivity to chemotherapeutics with CO treatment, we will combine the proposed strategy with current chemotherapy to eradicate tumours in animal models.


Participants :
- University of Cambridge (Royaume-Uni) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 183454.8 €