Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras PhD Project Template PI name & contact details: Thomas Ritter, Ph.D., Senior Lecturer in Medicine Phone: xx353-(0)91-495329, Fax: xx353-(0)91-495547 e-mail: thomas.ritter@nuigalway.ie School: School of Medicine Has project been agreed with head (or nominee) of proposed registration school? yes Research Centre / group affiliation: National Centre for Biomedical Engineering Science (NCBES) http://ncbes.eurhost.net/ Regenerative Medicine Institute (REMEDI) Research group / centre website: http://www.nuigalway.ie/remedi/ PI website / link to CV: http://ncbes.eurhost.net/bio/thomas-ritter.aspx Brief summary of PI research / research group / centre activity (2 or 3 lines max): My research group focuses on the development of novel gene and cell therapeutic strategies to prevent organ graft rejection and to characterise the underlying mechanisms. We use a range of techniques as appropriate for each project including tissue culture, molecular biology, protein biochemistry, gene therapy, flow cytometry, microscopy, small animal models and analysis of human biospecimens. Within the Immunology Group (Profs M. Griffin and R. Ceredig) in REMEDI we investigate the immunomodulatory properties of mesenchymal stem cells. Title & brief description of PhD project (suitable for publication on web): Enhancement of in vivo therapeutic properties of differentiated allogeneic mesenchymal stem cells by genetic modification Mesenchymal stem cells (MSCs) are a heterogeneous population of non-hematopoietic cells with multi-lineage potential. Therapeutic applications of MSCs that involve direct regeneration of mesenchymal tissues such as cartilage require that MSC differentiation along a single lineage can be achieved and maintained in vivo. The clinical success of such applications will require a detailed understanding of the in vivo immunologic responses to differentiated MSCs from autologous and allogeneic sources. Preliminary data from our laboratory indicate that chondrocyte-differentiated MSCs loose their immunosuppressive properties which may result in rapid immune mediated rejection in vivo. The impact of chondrocyte-differentiated MSCs on in vivo immunogenicity is of specific relevance to the use of MSCs for human cartilage repair. In this project the potential of genetic modification of chondrocyte-differentiated MSCs to reduce immunogenicity will be studied. MSCs will be genetically modified to express anti-inflammatory molecules such as Interleukin-10 and Programmed Death-Ligand 1, molecules which have been shown by us to effectively modulate immune responses (1). Immune responses to chondrocyte-differentiated allogeneic MSCs will be investigated in the rat osteochondral defect model and compared to undifferentiated MSCs. Persistence of the implanted cells and in vivo immune responses will be analysed. Therapeutic effects of implanted MSC populations on joint repair will also be examined. This project will elucidate the in vivo immunogenicity of chondrocyte-differentiated MSCs and improve the therapeutic efficacy of differentiated MSCs in vivo. 1. Nosov et al. Am. J. Transpl. 2012 12:1313-22 Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras Unique selling points of PhD project in NUI Galway: As a REMEDI member, the student will have access to the following: A number of core technical facilities in areas such as flow cytometry, microscopy, cell culture, histology, molecular biology etc A diverse range of additional subject-specific and non-specific didactic elements as part of the structured PhD programme (Regenerative Medicine Ph.D. programme). A wide range of expertise including the areas of stem cell biology, gene therapy, immunology, molecular biology, translational research A wide network of collaborating researchers in Ireland, Europe, the US and worldwide Name & contact details for project queries, if different from PI named above: Please indicate the graduates of which disciplines that should apply: Biomedical Sciences, Biology, Cell biology, Ciência sem Fronteiras / Science Without Borders Priority Area: Please indicate the specific programme priority area under which the proposed PhD project fits- choose only one (tick box): Engineering and other technological areas Pure and Natural Sciences (e.g. mathematics, physics, chemistry) Health and Biomedical Sciences Information and Communication Technologies (ICTs) Aerospace Pharmaceuticals Oil, Gas and Coal Renewable Energy Minerals Biotechnology Nanotechnology and New Materials Technology of prevention and remediation of natural disasters Biodiversity and Bioprospection Marine Sciences Creative Industry New technologies in constructive engineering Please indicate which of the following applies to this project (referring to Science Without Borders arrangements): Suitable only as a Full PhD (Y/N): _ ___Y_ Available to candidates seeking a Sandwich PhD arrangement (Y/N): ___Y__ Suitable for either/Don’t know: _____