Development of preclinical models of undifferentiated pleomorphic soft tissue sarcoma and identification of therapeutic targets

Applications are invited for a Melville Trust funded PhD training position at the University of Edinburgh, to be hosted jointly between the Edinburgh Cancer Research UK Centre (Prof Valerie Brunton) and the Centre for Genomic & Experimental Medicine (Prof Donald Salter) at the Institute of Genetics & Molecular Medicine http://www.ed.ac.uk/igmm. The Institute of Genetics & Molecular Medicine has around 120 students onsite and provides a vibrant research environment.

Undifferentiated pleomorphic soft tissue sarcoma (UPS) is the commonest sarcoma subtype. However, in common with other subtypes there are limited treatment options and median survival remains in the range of one to two years. Lack of good preclinical models is one confounding factor in the development of new therapies. Based on our recent sequencing data of human UPS a genetically engineered mouse model of UPS, driven by loss of p53 and Rb that is amenable to drug intervention studies will be established. In addition we will use primary patient derived cultures. Initially these will be used to interrogate the role of the mitochondrial translation pathway (MPT) in UPS, as combined loss of p53 and Rb in breast cancer is known to be associated with increased activity of the MPT pathway and has emerged as a possible therapeutic target. Image-based drug screens will be carried out to identify further vulnerabilities and possible combination therapies using drug-screening platforms available at the Edinburgh Cancer Drug Discovery Unit. More complex 3-dimensional and tissue-based models of UPS will be used to validate prioritized compounds and combinations.

This project will provide the student with training in use of patient-derived 3D models and genetically engineered mouse models and drug discovery pipelines, which are central to translating basic research findings. They will gain invaluable experience in this key strategic area and will benefit from a multidisciplinary supervisory team spanning basic and translational research to the clinic. The project builds on an interest in sarcoma in Edinburgh and will benefit from current projects focused on understanding the genetic and immune landscape of human UPS, while providing invaluable models for evaluating further treatment options such as immune checkpoint inhibitors.

Applicants should send a covering letter, stating why they are interested in the project, along with an up-to-date CV, which includes two academic referees to [Email Address Removed] by 21st July 2017.