PhD Study : Investigating the links between expression, function and epigenetic regulation of microRNAs.

Summary

Background

MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression by interacting with messenger RNAs (mRNAs). There is much hope that microRNA profiling can be a potentially valuable tool for improving the prognosis, diagnosis and treatment of disease (1), but there remains a significant gap in our knowledge about how exactly they function.

In our laboratory, we are interested in how the regulation of specific miRNAs, and their gene networks, can contribute to disease progression. In particular we are interested in how epigenetic mechanisms, such as DNA methylation can impact upon miRNA expression in different diseases, including  cancer (2) and glaucoma (3).

The current project will investigate this by utilising a combination of in vitro, in vivo and in silico models to explore the regulation and functionality of various miRNAs, including miR-145 and the miR-200 family. This project brings together the research interests of the three listed supervisors, making it a strategic area of investigation for the Genomic Medicine Research Group.

Methods

The methods, equipment and expertise outlined below are routinely used in the laboratories of the supervisors. Papers featuring similar experimental approaches have been published by them (4-7).

*2D & 3D Cell culture (cell-lines, primary cells, spheroids) *PCR Expression Analysis of miRNA

*Analysis of DNA methylation in miRNA regions by MS-PCR, bisulfite sequencing, COBRA analysis

*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.

Aims & objectives

a.To identify and select miRNAs for investigation

b.To assess how methylation impacts upon expression of selected miRNAs

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

d.To explore clinical significance of selected miRNAs through in silico analysis of online datasets

e.To evaluate the potential of miRNA (and methylation) profiling as diagnostic/prognostic biomarkers in disease

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

1.Rupaimoole & Slack, Nat Rev Drug Discov. 2017 Mar;16(3):203-222.

2.Piletič & Kunej, Arch Toxicol. 2016 90(10):2405-19.

3.Liu et al, Curr Genomics. 2013 14(3):166-72

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

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

6.Lechner et al, Invest Ophthalmol Vis Sci. 2013 54(8):5266-72.

7.Irwin et al, Genomics. 2014 104(5):383-92.

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.

• First Class Honours (1st) Degree
• Masters at 65%
• Research project completion within taught Masters degree or MRES
• Practice-based research experience and/or dissemination
• Experience using research methods or other approaches relevant to the subject domain
• Work experience relevant to the proposed project
• Publications - peer-reviewed
• Experience of presentation of research findings
• A comprehensive and articulate personal statement
• 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