This is a Medical Research Scotland (http://www.medicalresearchscotland.org.uk) funded PhD Studentship to be delivered jointly by the named University and Company. The Studentship is for three years and will provide the first-class academic and commercial training needed to equip the successful candidate for a science career in an increasingly competitive market.
"Specificity of fibroblast growth factor-induced signalling pathways in human tumours – identification of novel therapeutic targets?" to be delivered by the University of Dundee and Dundee Cell Products Limited (http://www.dundeecellproducts.com) [Company supervisor: Dr Francesco Rao].
Ovarian cancer is difficult to treat – it is often widespread at diagnosis, when treatment is palliative rather than curative. Patients are primarily treated by chemotherapy, but response is unpredictable and often limited by the development of drug-resistant disease. Recent developments in chemotherapy drug design reflect a move to more stratified treatment, where drug selection for individual patients is tailored to patient genotype or phenotype. Growth factors (e.g. epidermal (EGF), fibroblast (FGF), platelet-derived (PDGF) and vascular endothelial (VEGF)) and associated receptor tyrosine kinases (RTKs) regulate key signal transduction pathways frequently dysregulated in cancer. RTK pathways are common chemotherapy drug targets, but optimal patient selection and drug efficacy is limited by lack of target specificity and/or individuality in target gene expression. We are particularly interested in FGF signalling as we have shown that FGF expression varies widely, is increased in more advanced ovarian tumours and influences response to cisplatin and carboplatin, the chemotherapy drugs most commonly used to treat ovarian cancer patients (Smith et al, British Journal of Cancer 107, 1327-1336, 2012).
In this project, we will use a variety of complementary molecular biology approaches to further investigate specificity of FGF signalling in ovarian and other common cancers, and will characterise the phenotypic consequences of individuality in RTK pathway signalling. Transcriptomic and proteomic approaches will be used to investigate the phenotypic consequences of altered FGF signalling and to dissect the signalling cascades affected by manipulation of FGF pathway genes, while structurally and functionally diverse libraries of chemotherapy drugs and small molecule pathway inhibitors will be used to confirm our hypothesis that inter-patient differences in FGF signalling influences sensitivity to specific chemotherapy drugs which directly damage DNA.
We will investigate the mechanisms by which FGF signalling influences the DNA damage response, combining our laboratory studies with bioinformatics analysis of large public domain ovarian cancer datasets from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). Prioritised candidate genes will additionally be analysed in well-characterised clinical samples in collaboration with Tayside Tissue Bank and in the Dundee Ovarian Cancer (DOCS) study, a unique longitudinal study in which we are collecting serial plasma, serum and ascites samples from ovarian cancer patients as they progress through treatment.
Enquiries should be sent by email to Dr Gillian Smith: [email protected]
Candidates must have obtained, or expect to obtain, a first or 2.1 UK BSc Honours degree, or equivalent for degrees obtained outside the UK, in Biological or Biomedical Sciences, or a related discipline.
Applicants should send a CV, the contact details of 2 academic references (including email addresses) and a covering letter, explaining why the applicant wishes to carry out this project, by email to Dr Gillian Smith: [email protected]
Interviews are expected to take place approximately 4 weeks after the closing date for applications.
It is anticipated that the PhD Studentship will start in October 2016.