PhD Study : An integrative multi-omics approach to targeting cellular senescence as a drug repurposing strategy for age-related morbidities

Summary

Age is a major risk factor for various human diseases including cancers, dementia, and cardiovascular diseases. Senescence is a process where cells cease dividing and undergo distinctive phenotypic changes. Senescence has a key role in the aging process and has also been implicated as a major cause of age-related disease. The recent COVID-19 pandemic also clearly showed that age is a prominent risk factor for the severity of the disease.  Indeed SARS-CoV-2 induced senescence is not only a driver but also a therapeutic target in COVID-19. Targeting cellular senescence could potentially alleviate many age-related pathologies.

In this project, we aim to identify therapeutic candidates that could selectively eliminate senescent cells. Such drugs are often referred to as senolytics, which could contribute to the treatment of specific age-related diseases, and potentially could also improve the life and health span of aged individuals.  We propose to deploy an integrative multi-omics connectivity mapping approach to targeting cellular senescence as a drug repurposing strategy for potential applications in age-related diseases.

The overall aim of the project will be achieved through the following steps/objectives:

1) Integration of multiple streams and categories of data in public data repositories from cellular senescence and aging related studies, as well as in-house multi-omics datasets we have generated over the last two years utilizing several past and ongoing grants, including RNA-Seq, WGS, proteomics, and meta transcriptomics for 500 COVID-19 patients.

2) Construction of robust gene signatures for cellular senescence based on the integrative analysis of the multi-omics datasets.

3) Application of our established gene expression connectivity mapping framework to computationally screen a collection of over 1500 approved drugs for the identification of senolytics candidates.

4) In vitro validation of top 3-4 emerging drugs in appropriate lung or other cell line models.

AccessNI clearance required

Please note, the successful candidate will be required to obtain AccessNI clearance prior to registration due to the nature of the project.

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
• A comprehensive and articulate personal statement
• Research proposal of 1500 words detailing aims, objectives, milestones and methodology of the project
• A demonstrable interest in the research area associated with the studentship

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 70%
• Research project completion within taught Masters degree or MRES
• Experience using research methods or other approaches relevant to the subject domain
• Publications - peer-reviewed
• Publications record appropriate to career stage
• Experience of presentation of research findings

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