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 Co-PI name & contact details: Alexander Fluegel, M.D. Prof. for Neuroimmunology Institute for Multiple-Sclerosis-Research, University Medicine Goettingen, Germany. Phone 0049 551 39 13332 e-mail: fluegel@med.uni-goettingen.de School of Medicine (PI) School: 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/ Research group / centre website: Regenerative Medicine Institute (REMEDI) PI website / link to CV: http://ncbes.eurhost.net/bio/thomas-ritter.aspx http://www.nuigalway.ie/remedi/ Co-PI website / link to CV: http://www.neuroimmunologie.uni-goettingen.de 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, glycoimmunology, 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): Understanding the immunomodulatory properties of mesenchymal stem cells on “licensing” of pathogenic T cells in the lung Mesenchymal stem or stromal cells (MSCs) are a heterogeneous population of nonhematopoietic cells with multi-lineage potential. They can be isolated from bone marrow (BM) and other sources and have the capacity to extensively proliferate in vitro. Interestingly, it has also been demonstrated that MSCs possess immunomodulatory properties. Although MSCs have been administered to many patients in various clinical trials with beneficial effects the underlying mechanisms are not yet fully understood. Preliminary data from our group indicate that the majority of MSCs can be found in the lung 24h after systemic administration. Interestingly, the lung also plays a major part in the “licensing” of pathogenic T cells to enter the central nervous system in an autoimmune experimental encephalitis (EAE) model of Multiple Sclerosis (MS) (1). In this collaborative project we will generate MSCs from rat BM and after extensive in vitro analysis investigate if MSC-application is able to modulate the pathogenic properties of autoimmune T cells in a Lewis rat EAE model. MSCs and pathogenic T cells will be Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras labelled with fluorescent dyes and their migration and pathogenicity will be monitored by two photon intravital microscopy. Moreover, overexpression or siRNA knockdown of key molecules involved in MSC-immunomodulation or T-cell migration will be performed to understand the underlying mechanisms of immunomodulation/migration in this model. This research will significantly contribute to improve our understanding of the immunomodulatory properties of MSCs for future treatment of patients suffering from MS. 1. Odoardi et al., Nature 2012; 488: 675-679. 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 State of the art 2-photon intravital microscopy for monitoring in vivo cell migration and pathology in Goettingen 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, Pharmacology 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 Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras 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: _____