Version 2 Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras PhD Project Template Use one form per project Please complete & submit to international@nuigalway.ie as soon as possible, and by 27/11/2012 In your email, begin the subject line with [SWB] (be sure to use square brackets) to ensure that your email is filed correctly. Emails will be automatically filed PI name & contact details: School: Dr Roisin Dwyer Discipline of Surgery School of Medicine National University of Ireland Galway Phone +353-(0)91-524390, Fax: +353-(0)91-494509 Email: Roisin.dwyer@nuigalway.ie Medicine Has project been agreed with head (or nominee) of proposed registration school? Research Centre / group affiliation: Discipline of Surgery Research Group and National Breast Cancer Research Institute Research group / centre website: www.nuigalway.ie/surgery/research www.nbcri.ie PI website / link to CV: http://www.nuigalway.ie/surgery/research/roisin_dwyer.html Brief summary of PI research / research group / centre activity (2 or 3 lines max): Breast cancer is the core focus of this research group, with a number of different approaches to identifying novel therapeutic strategies under investigation. The work highlighted here investigates the potential of adult stem cells as vehicles for targeted delivery of therapeutic genes or their products to breast tumors, with a specific interest in imaging modalities to track MSC migration in vivo. Title & brief description of PhD project (suitable for publication on web): Mesencyhmal Stem Cell (MSC)-mediated Gene Therapy for Breast Cancer Despite improvements in detection and treatment, breast cancer incidence continues to rise. Although patients with early stage disease have an excellent prognosis, the outcome remains poor for those with metastatic disease. Mesenchymal Stem Cells (MSCs) are a subset of nonhaematopoietic multipotent cells found primarily within the bone marrow stroma. The ability of MSCs to specifically home to sites of tumours and their metastases, while escaping host immune Version 2 Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras surveillance holds tremendous promise for tumour targeted delivery of therapeutic agents. The proposed study will harness MSCs for tumour-specific delivery of genes to support both imaging of MSC migration in vivo, and ablation of breast cancer tissue following MSC engraftment. Previous studies performed by this research group and others support the feasibility of this approach: MSCs were engineered to express a gene to track migration in vivo and then injected intravenously into tumour bearing mice, followed by imaging. MSCs were shown to migrate specifically to the sites of tumours, after which their anti-cancer properties were activated. This resulted in a significant reduction of tumour growth. This exciting preliminary data was generated using models of localised breast cancer. The proposed study will translate this to clinically relevant models of metastatic disease, and determine the true potential of this novel therapeutic strategy for treatment of invasive breast cancer. Interactions between MSCs and cells in the primary tumour microenvironment will also be investigated to determine the role of these cells in disease progression. Unique selling points of PhD project in NUI Galway: This work represents a multidisciplinary international collaboration between groups at NUI Galway (Surgery, Regenerative Medicine, Physics), the University of Arizona Centre for Gamma Ray Imaging (Arizona, USA) and the Discipline of Endocrinology at the Mayo Clinic (Rochester, MN, USA). All of the required facilities and support required for the proposed project are available on site or adjacent to (Clinical Research facility) the University campus. Within the Discipline of Surgery, all equipment and resources required for tissue processing, storage and analysis are present, e.g.: Dedicated hoods for tissues homogenisation, RNA extraction and RQ-PCR respectively Fast RQ-PCR machine for large scale analysis of RNA from tissue samples- the PCR reaction is completed within 25mins GUAVA 8HT for analysis of primary cell populations and MSCs to confirm cell specific antigen expression profile Fluorescent microscope for analysis of PKH26 labelled MSCs within tissue sections Ventana machine for automated Immunohistochemical analysis of tissue sections Cell culture laboratory with dedicated incubators and hoods for both primary culture, and culture of cell lines Specialised In Vivo research facilities are also available on campus Name & contact details for project queries, if different from PI named above: Version 2 Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras Please indicate the graduates of which disciplines that should apply: Biomedical Science, Molecular 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)/Physical Sciences (Mathematics, Physics, Chemistry, Biology and Geosciences) Health and Biomedical Sciences / Clinical, Pré-clinical and Health Sciences X Information and Communication Technologies (ICTs), Computing Aerospace Pharmaceuticals Sustainable Agricultural Production Oil, Gas and Coal Renewable Energy Minerals, Minerals Technology Biotechnology Nanotechnology and New Materials Technologies for Prevention and Mitigation of Natural Disasters Bioprospecting and Biodiversity 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): _N____ Suitable for either/Don’t know: _____