PhD Study : Investigation of microRNA regulation and function in prostate cancer

Summary

MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression by interacting with messenger RNAs (mRNAs) from genes that encode proteins. The aberrant expression of miRNAs has been associated with various disease states, including prostate cancer.  There is much hope that microRNA profiling can be a potentially valuable tool for improving the prognosis, diagnosis and treatment of this diseases. However, there remains a significant gap in our knowledge about the role of miRNAs in prostate cancer development.

The functionality of many of these miRNAs remains unknown, so there is still a requirement for studies which can demonstrate experimental validation of miRNA target(s) and a measurable effect on cellular behaviour, in order to elucidate their mode of action. In our laboratory, we are interested in investigating how specific miRNAs can contribute to the progression of prostate cancer through their regulatory networks.

We have identified several miRNAs that remain poorly investigated in relation to prostate cancer and which therefore offer exciting possibility for novel discoveries. We are also interested in how expression of these miRNAs is regulated by (i) epigenetic mechanisms, such as DNA methylation, and (ii) tumour-specific characteristics, such as tumour hypoxia.

Our laboratory uses a variety of in vitro, in vivo and in silico models to investigate these phenomena. The current project will utilise a combination of these methods to identify and investigate miRNAs which play important roles in prostate cancer development.

Methods

The methods equipment and expertise outlined below are routinely used in the laboratories of both supervisors and papers featuring similar experimental approaches have been published by them.

*Cell culture of prostate cancer cells

*PCR Expression Analysis of miRNA

*Analysis of DNA methylation *Functional Analysis of selected miRNA - Transfection assays - Effect on protein expression (Western Blotting) - Validation of target(s) (PCR & luciferase reporter assay) - Cell behaviour bioassays (proliferation / apoptosis /invasion )

*Bioinformatic analysis & Data-mining of online clinical data repositories.

*Use of ‘R’ to probe datasets.

Hypothesis: Altered expression of miRNA promotes prostate cancer cell proliferation.

Aims & objectives

1.To identify and select miRNAs for investigation

2.To identify targets and carry out functional analysis of selected miRNAs

3.To assess how selected miRNAs are regulated

4.To identify clinical significance of selected miRNAs through in silico analysis of The Cancer Genome Atlas clinical datasets

5.To evaluate the potential of miRNA profiling as diagnostic/prognostic biomarkers in prostate cancer

Skills Required of Applicant

*Good Laboratory skills

*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

*Interest in bioinformatic analysis

References

Kanwal et al, Cancer Lett. 2017, 407:9-20.

Vanacore et al, Oncotarget. 2017, 8(30):50240-50251.

Lynch et al, Prostate 2016, 76(13):1146-5910.

Lynch et al, 2016 Prostate 76(7):637-48.

Nesbitt et al, Clin Cancer Res. 2017 23(7):1797-1808.

Essential criteria

Applicants should hold, or expect to obtain, a First or Upper Second Class Honours Degree in a subject relevant to the proposed area of study.

We may also consider applications from those who hold equivalent qualifications, for example, a Lower Second Class Honours Degree plus a Master’s Degree with Distinction.

In exceptional circumstances, the University may consider a portfolio of evidence from applicants who have appropriate professional experience which is equivalent to the learning outcomes of an Honours degree in lieu of academic qualifications.

• Sound understanding of subject area as evidenced by a comprehensive research proposal

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

• Completion of Masters at a level equivalent to commendation or distinction at Ulster
• Experience using research methods or other approaches relevant to the subject domain
• Work experience relevant to the proposed project
• Publications - peer-reviewed
• Publications record appropriate to career stage
• Experience of presentation of research findings
• A comprehensive and articulate personal statement
• Use of personal initiative as evidenced by record of work above that normally expected at career stage.
• Relevant professional qualification and/or a Degree in a Health or Health related area

Funding and eligibility

The University offers the following levels of support:

Vice Chancellors Research Studentship (VCRS)

The following scholarship options are available to applicants worldwide:

• Full Award: (full-time tuition fees + £19,000 (tbc))
• Part Award: (full-time tuition fees + £9,500)
• Fees Only Award: (full-time tuition fees)

These scholarships will cover full-time PhD tuition fees for three years (subject to satisfactory academic performance) and will provide a £900 per annum research training support grant (RTSG) to help support the PhD researcher.

Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Please note: you will automatically be entered into the competition for the Full Award, unless you state otherwise in your application.

Department for the Economy (DFE)

The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £19,000 (tbc) per annum for three years (subject to satisfactory academic performance).

This scholarship also comes with £900 per annum for three years as a research training support grant (RTSG) allocation to help support the PhD researcher.

• Candidates with pre-settled or settled status under the EU Settlement Scheme, who also satisfy a three year residency requirement in the UK prior to the start of the course for which a Studentship is held MAY receive a Studentship covering fees and maintenance.
• Republic of Ireland (ROI) nationals who satisfy three years’ residency in the UK prior to the start of the course MAY receive a Studentship covering fees and maintenance (ROI nationals don’t need to have pre-settled or settled status under the EU Settlement Scheme to qualify).
• Other non-ROI EU applicants are ‘International’ are not eligible for this source of funding.
• Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Due consideration should be given to financing your studies. Further information on cost of living