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:
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.
If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.
The University offers the following levels of support:
The following scholarship options are available to applicants worldwide:
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.
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.
Due consideration should be given to financing your studies. Further information on cost of living
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).
Submission deadline
Friday 5 February 2021
12:00AM
Interview Date
Weeks commencing 15th and 22nd March 2021
Preferred student start date
Mid-September 2021
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