PhD Study : Role and composition of muscle vesicles in Amyotrophic Lateral Sclerosis

Apply and key information  

Summary

Amyotrophic Lateral Sclerosis (ALS), the most common form of motor neuron disease, is characterized by the degeneration of motor neurons and a short life expectancy. ALS is a genetically complex multi-systemic disease where many tissues are affected including muscle tissue (1). In recent work, we have shown that muscle cells from sporadic ALS patients secrete neurotoxic vesicles, which are toxic to human induced pluripotent stem cell (iPSC) motor neurons. As muscle cells present a strong vesicle phenotype across all ALS patients studied, we hypothesized that vesicles and their contents could be sources of biomarkers and therapeutic targets for the disease, and that patient muscle cells represent an important disease model for drug discovery.

Currently, there is no definitive diagnostic test for ALS, and patients often need to undergo multiple invasive investigations for their diagnosis, with a typical diagnostic delay of 9-15 months from onset to diagnostic confirmation (2,3). Considering that the average survival from onset is 2-4 years and that efficacy of treatment is improved by early initiation, improved diagnostic speed would be beneficial to the treatment of ALS (4). There is an urgent need to identify disease-specific biomarkers that would be useful to diagnose patients and monitor effects of treatments.

Purpose: The candidate, in collaboration with other team members, will test the potential of muscle vesicles and their contents as biomarkers to diagnose and to track disease progression through samples from current UK and French collaborations and using novel methodology developed by the team (5), and will work towards the testing of different drugs to correct the ALS phenotype in in-house immortalized muscle cell models.

Key skills required:

  • Have a keen interest in neurodegenerative diseases and motor neuron diseases *Have excellent communication and interpersonal skills
  • Competence in wet lab experiments (cellular and molecular biology: eg: cell culture or ELISA or PCR/RT-qPCR or Western blot)
  • Rigorous management and organisation of data
  • Demonstrate the ability to work as part of a large multidisciplinary team
  • Ability to use initiative and work flexible hours
  • Willing to learn new skills and techniques, including laboratory techniques
  • Ability to deal effectively with administrative tasks

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
  • Clearly defined research proposal detailing background, research questions, aims and methodology

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
  • Sound understanding of subject area as evidenced by a comprehensive research proposal
  • Work experience relevant to the proposed project
  • Publications record appropriate to career stage
  • 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

Recommended reading

1. Le Gall, L. et al. Molecular and Cellular Mechanisms Affected in ALS. J. Pers. Med. 10, 101 (2020).

2. Chiò, A. & Traynor, B. J. Motor neuron disease in 2014. Biomarkers for ALS--in search of the Promised Land. Nat. Rev. Neurol. 11, 72–4 (2015).

3. Vijayakumar, U. G. et al. A Systematic Review of Suggested Molecular Strata, Biomarkers and Their Tissue Sources in ALS. Front. Neurol. 10, (2019).

4. Sawada, H. Considerations for pharmacotherapy use in patients with amyotrophic lateral sclerosis: the earlier it starts, the better the results. Expert Opin. Pharmacother. 20, 1671–1674 (2019).

5. Le Gall, L. et al. Optimized method for extraction of exosomes from human primary muscle cells. Skelet. Muscle 10, 20 (2020).

The Doctoral College at Ulster University

Key dates

Submission deadline
Friday 5 February 2021
12:00AM

Interview Date
Weeks commencing 15th and 22nd March 2021

Preferred student start date
Mid-September 2021

Applying

Apply Online  

Contact supervisor

Dr Stephanie Duguez

Other supervisors