PhD Study : Senolytic compounds as new medicines for chronic diseases of ageing.

Apply and key information  

Summary

Ageing is thought be a normal physiological process, however ageing is the single biggest risk factor for variety of chronic diseases. Little is known about the molecular processes that can be targeted to delay ageing. One such process is cellular senescence. Senescent cells irreversibly stop dividing and enter a state of permanent growth arrest.  As we age, the capability of the immune system to target and eliminate senescent cells is decreased and we start to accumulate these in our body. Escape from senescence is carcinogenic, hence senescence serves a vital tumour suppressive function.

These accumulating senescent cells in our bodies secrete a variety of chemical signals that can cause progressive organ dysfunction. Hence, targeting senescence in older individuals maybe vital to treat chronic diseases of ageing. Compounds that remove such cells in organisms are called senolytics. One disease area that we hope to target using senolytics is Atrial Fibrillation (AF). AF is the most common disturbance of heart rhythm in all adult age groups. To control symptoms from AF many patients receive medications to control the heart rate and/or the rhythm. The majority of these anti-arrhythmic treatments target symptoms and can have serious side effects. Hence, development of new and innovative medicines such as senolytics is needed urgently.

Our hypothesis is that targeted elimination of senescenct cells in heart can cure AF. We will target senescence using various small molecue drugs and novel natural compounds including a panel of  >1,000 FDA approved drugs in the LINCS database for  repurposing screen. We have developed and tested special bioinformatics algorithms in the framework of gene expression connectivity mapping and successfully applied this advanced technique to repurpose drugs for a number human diseases including cancers [Wen et al 2017, Oncotarget] and cystic fibrosis [Malcomson B, et al. 2016 PNAS].

Recently, there has been an exponential increase in publication of omics datasets (including many by Dr Rai) specific to senescence. Using machine learning and artificial intelligence these datasets will be mined for pathways and drug combinations that can “push” senescent cells to apoptosis. The bioinformatic discovery will be complemented by in vitro studies as follows.

Firstly we will use our ER Ras senescence model system. ER Ras is an inducible senescence model, where we have engineered HRasG12V oncogene into IMR90 cells and these can be made senescent just by adding tamoxifen.

Second model system to be utilized will the etoposide induced DNA damage model of senescence. Here, we will treat atrial specific cardiomyocytes with 50 uM of etoposide for 24 hours to induce senescence. For a compound to be senolytic, it would have to kill senescent cells in both models as opposed to proliferating control cells. We believe this could lead to discovery of innovative treatment modalities for AF.

The proposed 3-year project will be based at the Centre for Personalized Medicine (CPM) under the supervision of Dr Rai, Dr McGilligan, Dr Zhang, research lecturers and alongside Professor Bjourson, centre director. The project will also involve active collaboration with Professor Peace, Consultant Cardiologist at Altnagelvin Hospital.

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

The Doctoral College at Ulster University

Key dates

Submission deadline
Monday 18 February 2019
12:00AM

Interview Date
w/c 11, 18 and 25th March 2019

Preferred student start date
September 2019

Applying

Apply Online  

Contact supervisor

Dr Taranjit Singh Rai

Other supervisors