Housden Group Available PhD Opportunities Self-funded PhD positions Project 1: Developing a preventative therapy for Neurofibromatosis type 1 tumours. Supervisors: Associate Prof Benjamin Housden, Dr. Kirsty Wan and Prof Steven West The aim of this project is to investigate the possibility of developing a preventative treatment for tumours associated with Neurofibromatosis type 1 (NF1). This is important because patients live with the constant fear of developing disfiguring and potentially life threatening tumours throughout their lives and there are currently no effective treatments available. A preventative drug would allow patients to live without this fear and without the disfigurements caused by skin tumours. This project therefore has the potential to result in significant benefits to the quality of life of people with NF1. NF1 tumours form when the NF1 gene is mutated in a single cell within the patient’s body. This mutation stimulates the cell to grow and divide, resulting in a tumour. Our previous work suggests that cells contain mechanisms that allow them to adapt and survive following mutation of a gene like NF1. During this project, we will look at how gene expression changes over time following loss of NF1 gene function. This approach will allow us to investigate the adaptive mechanisms to identify the genes and molecular pathways that are altered immediately following mutation of the NF1 gene. We will then test whether existing drugs, that are known to be safe for use in humans, can be repurposed to target these mechanisms. Our hypothesis is that by inhibiting these adaptive mechanisms, cells will no longer be able to survive mutation of the NF1 gene and will therefore be killed before a tumour forms. By the end of this project, we expect to have mapped the mechanisms by which cells adapt to loss of the NF1 gene. In addition, we expect to identify existing drugs that have potential to be repurposed as a preventative therapy for NF1 tumours. By focusing on existing drugs, our results can be rapidly developed for clinical use, resulting in benefits to NF1 patients as soon as possible. Email b.housden@exeter.ac.uk to apply Project 2: Understanding motor neuron disease using a powerful combination of model systems Supervisors: Professor Benjamin Housden, Professor James Hodge and Professor Krasimira Tsaneva-Atanasova The aim of this project is to understand the mechanisms that cause motor neuron disease (MND) so that new treatments can be developed. This is important because MND is a devastating disease that results in death only three years after diagnosis. There are no cures and our understanding of why people develop the disease is limited. This project will use cutting edge techniques to investigate the mechanisms underlying MND, leading to effective therapies in the future. Email b.housden@exeter.ac.uk to apply Project 3: Development of novel drug treatments for prostate cancer Supervisor: Professor Benjamin Housden, Professor Mike Weedon, Professor Seb Oltean and Professor Nic Harmer Prostate cancer is one of the most common forms of cancer and despite available treatments, over 300,000 men die from this disease each year globally. It is therefore vital that we identify new therapies to treat this disease. In our previous work, we have shown that by combining human genomic analysis with genetic screens in cultured cells, it is possible to identify genes associated with prostate cancer that were missed by either approach alone. Using this method, we have already identified two new prostate cancer-associated genes. So far, we have only applied this approach on a small scale. In this project, the student will first analyse human genome data to identify genes involved in prostate cancer. Next, the candidate genes will be screened in cell culture models to validate those that selectively kill prostate cancer cells. Finally, the student will learn how to apply in silico drug screening methods to prioritise candidate targets for drug development. Email b.housden@exeter.ac.uk to apply