Genetically dissecting the cell biology of secretory cells in the Drosophila accessory gland as a model for prostate biology and cancer
Supervisor: Dr Clive Wilson, Dr Deborah Goberdhan & Professor Freddie Hamdy
Prostate cancer is the leading cause of cancer deaths in males, yet compared to other cancers, we know relatively little about the mechanisms that underlie prostate tumour progression and the associated pathologies, such as bone remodelling by tumour metastases, or indeed the basic biology of the normal prostate. In a collaborative project involving Drosophila developmental and reproductive biologists, cancer geneticists and clinicians, we are developing the accessory gland in Drosophila as a model to study prostate biology. This organ shares several functional similarities with the mammalian prostate, secreting a cocktail of proteases and glycoproteins into the seminal fluid, which are essential for sperm activation and fertility1,2. We have shown that a specific secretory cell type in this gland, the secondary cell, has remarkable properties, growing selectively as males age and mate, and sporadically climbing out of the epithelium and being transferred to females upon mating3. The signalling pathways regulating these properties also play a key role in prostate growth and metastasis.
We have more recently found that secondary cells share other cell biological properties with the prostate. The successful applicant for this project will investigate the functions of a number of signalling cascades linked to prostate cancer and progression, that we have found influence these properties in flies and will then collaborate with researchers studying prostate cancer biology to test whether these signals play a similar role in these latter cells. Ultimately these studies may suggest new strategies to treat prostate cancer in the clinic. There will be training opportunities in a broad range of approaches used by all the labs involved, including advanced cell biological techniques, molecular genetics and transgenic technology, Drosophila genetics, cell physiology, human cell culture and the dissection of signalling cascades. The student will collaborate with a dynamic team of researchers studying this problem in multiple research groups using different model systems.
Funding: Students would compete for Oxford-based funding
Contact details: Clive Wilson
Applications by: 4th January 2013 https://apply.embark.com/grad/Oxford/16/
1. Wolfner, M. F. Tokens of love: functions and regulation of Drosophila male accessory gland products. Insect Biochem. Mol. Biol. 27, 179-192 (1997). 2. Rylett, C. M., Walker, M. J., Howell, G. J., Shirras, A. D. and Isaac, R. E. Male accessory glands of Drosophila melanogaster make a secreted angiotensin I-converting enzyme (ANCE), suggesting a role for the peptide-processing enzyme in seminal fluid. J Exp Biol. 210, 3601-3606 (2007). 3. Leiblich et al. Bone morphogenetic protein-and mating-dependent secretory cell growth and migration in the Drosophila accessory gland. PNAS USA. In press.