Agency: Cordis | Branch: H2020 | Program: ERC-STG | Phase: ERC-StG-2014 | Award Amount: 1.49M | Year: 2015
The development of vaccines for the treatment of infectious diseases, cancer and autoimmunity depends on our knowledge of T-cell differentiation. This proposal is focused on studying the thymus, the organ responsible for the generation of T cells that are responsive against pathogen-derived antigens, and yet tolerant to self. Within the thymus, thymic epithelial cells (TECs) provide key inductive microenvironments for the development and selection of T cells that arise from hematopoietic progenitors. As a result, defects in TEC differentiation cause syndromes that range from immunodeficiency to autoimmunity, which makes the study of TECs of fundamental, and clinical, importance to understand immunity and tolerance induction. TECs are divided into two functionally distinct cortical (cTECs) and medullary (mTECs) subtypes, which derive from common bipotent TEC progenitors (TEPs). Yet, the genetic and epigenetic details that control cTEC/mTEC lineage specifications from TEPs are unsettled. My objectives are to identify TEC progenitors and their niches within the thymus, define new molecular components involved in their self-renewal and lineage potential, and elucidate the epigenetic codes that regulate the genetic programs during cTEC/mTEC fate decisions. We take a global approach to examine TEC differentiation, which integrates the study of molecular processes taking place at cellular level and the analysis of in vivo mouse models. Using advanced research tools that combine reporter mice, clonogenic assays, organotypic cultures, high-throughput RNAi screen and genome-wide epigenetic and transcriptomic profiling, we will dissect the principles that underlie the self-renewal and lineage differentiation of TEC progenitors in vivo. I believe this project has the potential to contribute to one of the great challenges of modern immunology modulate thymic function through the induction of TEPs - and therefore, represents a major advance in Health Sciences.
Agency: Cordis | Branch: H2020 | Program: MSCA-IF-EF-ST | Phase: MSCA-IF-2015-EF | Award Amount: 148.63K | Year: 2016
Nucleotides are the building blocks of nucleic acids and have emerged as significant determinants in energy transfer and signalling. Four nucleotides are known to function as signalling molecules in bacteria, namely the cyclic mono-nucleotides cAMP and cGMP, and the cyclic di-nucleotides c-di-AMP and c-di-GMP. These molecules play specific and distinct roles in many bacterial species, and can co-exist within a single bacterial cell. Whereas the diversity of cyclic nucleotide signalling is now starting to be uncovered, very little is known about their coordination in the control of their respective signalling pathways. Specifically, in the human pathogen Listeria monocytogenes, agent of a life-threatening and foodborne disease, it is known that both cyclic di-nucleotides c-di-AMP and c-di-GMP are produced but the production of cAMP and cGMP, as well as the contribution of the four nucleotides to the virulence mechanisms deployed by L. monocytogenes is yet to be uncovered. Using multidisciplinary approaches, the present proposal aims to 1) investigate the production of cAMP and cGMP, 2) identify new signalling pathways governed by the different cyclic nucleotides, and 3) uncover their role in physiology and pathogenesis. The overall impact of this proposal can open up the field to novel concepts and provide a basis for the study of cyclic nucleotide crosstalk.
Agency: Cordis | Branch: H2020 | Program: CSA | Phase: INFRADEV-2-2015 | Award Amount: 1.50M | Year: 2016
Euro-BioImaging (EuBI) is the pan-European research infrastructure project for imaging technologies in biological and medical sciences and has been on the ESFRI Roadmap since 2008. In close match with the scope and objectives of the INFRADEV2 call, Preparatory Phase II (PPII) funding will enable EuBI: to finalize the submission and approval procedure of its ERIC statutes with the EC and bring them to signature by the EuBI Member States and EMBL to launch the EuBI-ERIC; obtain commitments for the sustainable funding for the EuBI-ERIC by its Member States; implement the operational EuBI Hub and recruit its staff to provide user access and services; define and sign the service level agreements between EuBI-ERIC and the 1st generation of EuBI Nodes; establish a procedure to increase EuBI-ERIC membership, so that new countries can continuously join the EuBI-ERIC with clear national benefits and contributions. From Dec 2010 until May 2014, EuBI successfully completed its EU FP7-funded Preparatory Phase I, which addressed key technical and strategic questions and provided a blueprint for infrastructure implementation. 14 European countries (BE, BG, CZ, FI, FR, IL, IT, NO, PL, PT, SK, ES, NL, UK), and the PPI coordinator EMBL have signed the EuBI Memorandum of Understanding to jointly undertake the remaining steps required to draft and submit the EuBI ERIC application to the EC. The MoU signatories constitute the EuBI Interim Board (IB), which now governs the Interim Phase. To maintain the successful momentum of Member State engagement, the EuBI PPII project consortium comprises and is fully supported by all IB Members. We have jointly defined clear and measurable objectives that will bring EuBI to full maturity in order to start operation and provide its services to European researchers immediately upon launch of the EuBI-ERIC. The award of PPII funding would leapfrog the start of EuBI-ERIC user access and service provision by at least 1,5 years time or more.
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: NMP-06-2015 | Award Amount: 4.99M | Year: 2016
FOLSMART will bring to phase I clinical trials novel folate-based nanodevices (FBN) for the treatment of rheumatoid arthritis (RA). These nanodevices for folic acid (FA)-mediated targeting of activated macrophages showed improved clinical scores in a mouse model of RA when compared to methotrexate (MTX), a first-line drug therapy for the treatment of RA. In this way, FBN will be benchmarked against this drug. MTX has significant associated toxicity and second line biological therapies poses a great economic burden to hospital/public health systems. In parallel, nanodevices encapsulating Sulfasalazine (SSZ), will be tested. SSZ is a second line indication for the treatment of RA, unresponsive to MTX or MTXintolerant patients. Furthermore, FOLSMART propose the optimization of mechanisms for the release of the drugs, through pH and temperature sensitive nanodevices. An exploitation and business plans will be elaborated. In parallel, initial economic evaluation of all proposed treatments will be performed to validate these claims. Specific technological objectives of FOLSMART will be: Good Manufacturing Practice (GMP) production of the FBN based therapies which have been positively bench-marked in the previous FP7 European project NANOFOL in comparison with the use of MTX in a RA mouse model: -Liposomal MTX and SSZ with FA-neck domain peptide as targeting agent -Nanoparticles from HSA-FA/MTX conjugates and SSZ -Optimization of mechanisms of drug release and application to other fields Pre-clinical development on RA models -Toxicology and pharmacokinetics, to determine tolerability and efficacy benefit in two animal models rat and dog, under Good Laboratory Practice (GLP) standards -Genotoxicity and Carcinogenicity Phase I clinical trials of the best therapies bench marketed against MTX -Nanodevices with MTX and SSZ will offer improved tolerance and greater efficacy meaning that patients who do not do well on MTX will have cost-effective alternatives.
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.3.4-2 | Award Amount: 7.61M | Year: 2014
The infectious diseases burden imposed by the parasites of Trypanosomatidae family represents a huge problem on peoples lives in countries where these diseases are endemic. Problems associated with existing drugs include inefficient delivery, insufficient efficacy, excessive toxicity and increasing resistance. New drugs are urgently needed now and in the foreseeable future. The New Medicine for Trypanosomatid Infections (NMTrypI) consortium uses a highly interdisciplinary approach to optimize pteridine, benzothiazole and miltefosine derivatives, as well as natural products against Trypanosomatids. The lead compounds target mechanisms that are associated with protozoa virulence and pathogenicity. The major objectives of this 3-year project are: i) development of drug leads which may be used in combination with a known or an investigational drugs, by using a common drug discovery platform established by experts in their respective fields, ii) development of pharmacodynamic biomarkers enabling the proteomic profiling of compound efficacy and early identification of drug resistance. NMTrypI addresses sleeping sickness, leishmaniasis, and Chagas disease. The partners are SMEs (5) and academics (8) in Europe and in disease-endemic countries (Italy, Greece, Portugal, Sudan, and Brazil). The new platform enables high throughput screening of compound libraries, lead development, testing in relevant animal models, as well as toxicology and safety testing. NMTrypI will translate drug leads into drug candidacy through 6 scientific work packages (WPs1-6) supported by two transversal WPs dedicated to project dissemination and management. The major strength of the consortium lies in the complementary partnersexpertise and the integrated platform that will provide: - at least 1-2 innovative, less toxic and safer drug candidates for Trypanosomatid infections compared to existing ones, - early phase biomarkers for efficacy prediction (overall improved efficacy and safety)