Regulation of microRNA by DNA methylation in prostate cancer

Supervisors: Dr Declan McKenna, Professor Colum Walsh

Project Description
The role of epigenetic regulation in the onset of cancer is now well established. In prostate cancer (PCa), the use of epigenetics-based markers is believed to hold great potential for PCa diagnosis and prognosis, although continued research on different genes is required if this approach is to gain widespread acceptance. A recently discovered class of non-coding genes called microRNAs (miRNAs) may help prove this potential as there is increasing evidence that many of them are also epigenetically regulated. In PCa, several miRNAs express abnormally, suggesting they may be useful in the diagnosis, prognosis, and potential therapeutic intervention of this disease. It has also become apparent that many miRNAs are controlled by epigenetic mechanisms and several tumour suppressor miRNAs have now been shown to be silenced by hypermethylation in a range of tumour types, including PCa.

In our laboratory, we have identified a number of miRNAs which are downregulated in PCa cell lines and which show changed expression response to depleted levels of DNA Methyltransferase 1 (DNMT1). We have also profiled miRNA expression in a panel of biopsy specimens in collaboration with colleagues at Altnagelvin Area Hospital (7,8). We now want to further investigate selected miRNAs from these lead candidates to confirm which are under epigenetic regulation and which have potential value as biomarkers for monitoring PCa progression.
The methods outlined below are routinely used in the laboratories of both supervisors and papers featuring similar experimental approaches have been published by them (7-10). The equipment and expertise available in the labs means there should be minimum difficulty in commencing experimental work.

Skills required of applicant
• Good Laboratory skills (Experience in cell culture, PCR, methylation analysis, microRNA anaylsis an advantage)
• Good oral and written presentation skills
• Good critical thinking and analytical skills
• Good IT skills
• Good work ethic and ability to work independently
• Experience of biostatistics and using statistical packages (e.g. SPSS)
• Interest and/or experience in bioinformatic analysis

References and additional links
For more information on this project, the supervisory team and graduate studies at Ulster, please visit
http://www.science.ulster.ac.uk/gradschool/biomedical/

How to apply for this project:
http://www.ulster.ac.uk/research-and-innovation/phdresearch-degrees/how-to-apply

Closing date for Applications is 24 February 2017.

Funding Notes
The Department for the Economy (DfE) (formerly called Department for Employment and Learning (DEL))
The University has DfE research studentships available for PhD projects. These pay tuition fees and an annual maintenance award of not less than £14,553 per annum. These awards are open to holders of, or those expected to obtain, first or upper second class honours degrees and cover fees at the home rate and, for applicants with UK residence only, a maintenance allowance. Non-UK residents who hold ordinary EU residence may also apply but, if successful, will receive fees only. Applicants should indicate in the appropriate box on their University application form that they wish to apply for a DfE award. The closing date for receipt of applications will be 24 February 2017. Information on terms and conditions for DfE awards, including eligibility, can be found here: DfE Terms and Conditions for 2016/2017

Vice-Chancellor's Research Scholarships (VCRS)
A number of University funded VCRS will be available for PhD projects at Ulster. These awards are open to applicants who hold or, expect to obtain, a first or upper second class honours degree. They will cover tuition fees and a maintenance award of not less than £14,553 per annum for three years. Applications are invited from UK, European Union and overseas students. Applicants with up to one year’s current or previous registration for PhD at any institution may be considered for an award subject to the applicant providing evidence of good academic progress, formal release from all IP restrictions and ethical approval (if required). Three-year awards may be allocated to such applicants where they are taking-up a new project at Ulster. Applicants should indicate in the appropriate area on their University application form that they wish to apply for a University Studentship/VCRS award. The closing date for receipt of applications will be 24 February 2017. Information on terms and conditions for VCRS awards, including eligibility, can be found here: VCRS Terms and Conditions for 2016/2017