Dr Judith Sleeman
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
There is an increasing appreciation of potential links between SMA (Spinal Muscular Atrophy) and ALS (Amyotrophic Lateral Sclerosis) at the molecular level. Proteins such as FUS and TDP43/TARDBP, implicated in ALS pathology share a number of features with the SMN protein, which is deficient in SMA. Each has multiple roles within cells, localizing both to the nucleus and to the cytoplasm and each has been found in sub-cellular structures whose existence is proposed to increase local concentrations of proteins and RNAs, contributing to the efficiency of cellular processes.
Using microscopy and proteomics, we have recently uncovered changes in post-translational modifications in cell-culture models of ALS, which have the potential to impact on cellular pathways involved in SMA pathology. This project will use a combination of protein analysis with fixed and live cell microscopy to investigate this intersection further. The combination of molecular and cell culture techniques with analysis of a number of whole-animal models of both SMA and ALS provides a unique opportunity to search for similarities at the molecular level that may be of pathological relevance for both conditions.
Prerequisites
A suitable student will have a background in cell and molecular biology, with experience in cell culture, microscopy and the analysis of cellular proteins.
Essential skills would be general competence in laboratory bench-work and scientific writing.
Please contact your intended supervisor to discuss the project and your suitability for it before submitting your application.
The project is a part of SPRINT-MND/MS, a new Scotland-wide PhD scheme for research into motor neurone disease and multiple sclerosis. Projects, encompassing a wide range of topics including laboratory, clinical, and social sciences, are available at Aberdeen, Dundee, Edinburgh, Glasgow and St Andrews Universities. This exciting initiative provides a great opportunity for budding researchers in any field related to MND or MS to join Scotland’s network of world-leading scientists and health professionals. Find more information here: http://www.edneurophd.ed.ac.uk/sprint-mndms-phd-programme
Funding Notes
Studentships are for three years and include a standard non-clinical stipend*, UK/EU fees* and an allowance for consumables and travel. The cohort of SPRINT students will also be offered opportunities to attend clinics and meet patients, undertake ‘taster’ placements in a different field, and participate in public engagement and researcher networking events.
*Clinical and/or non-UK/EU applicants are eligible to apply. However, because any shortfall in stipend or fees must be met by the supervisory team, written agreement from the supervisor must accompany the application.
References
Prescott AR, Bales A, James J, Trinkle-Mulcahy L, Sleeman JE. Time-resolved quantitative proteomics implicates the core snRNP protein SmB together with SMN in neural trafficking. J Cell Sci. 2014 Feb 15;127(Pt 4):812-27. doi: 10.1242/jcs.137703.
Sleeman JE, Trinkle-Mulcahy L. Nuclear bodies: new insights into assembly/dynamics and disease relevance. Curr Opin Cell Biol. 2014 Jun;28:76-83. doi: 10.1016/j.ceb.2014.03.004.
Dawn of a new therapeutic era for spinal muscular atrophy. Gillingwater TH. Lancet. 2016 Dec 6. pii: S0140-6736(16)32390
Restoration of SMN in Schwann cells reverses myelination defects and improves neuromuscular function in spinal muscular atrophy.
Hunter G, Powis RA, Jones RA, Groen EJ, Shorrock HK, Lane FM, Zheng Y, Sherman DL, Brophy PJ, Gillingwater TH.
Hum Mol Genet. 2016 Jul 1;25(13):2853-2861.