FST21: Investigation of retroviruses in the pathogenesis of Motor Neuron Disease (MND)
Amyotrophic Lateral Sclerosis (ALS), also known as motor neuron disease (MND), is a fatal neurologic disorder of unknown etiology, characterized by the degeneration of motor neurons leading to paralysis and death from respiratory failure. Viral involvement in the etiology of sporadic ALS (sALS) has been suspected, with most focus on Human Endogenous Retroviruses (HERVs), being remnants of ancient germ line infections with exogenous retroviruses, that have been genetically fixed and vertically transmitted millions of years ago.
In a previous study, we found evidence for retroviral involvement in ALS by demonstrating cell-free reverse transcriptase (RT) activity (a generic screening method for retroviruses) in the serum of 50% of patients with sALS compared with 7% in controls. The primary aim of this proposal is to clarify the role of HERVs in sALS in order to identify potential new avenues for diagnosis and treatment of ALS which are lacking to date. Initial screening will focus on HERV-K and HERV-W, due to the presence of complete open reading frames and the ability to form virus like particles. Quantitative real-time PCR (qPCR) will be performed to measure HERV RNA expression levels in serum, CSF and post-mortem brain tissue in sALS patients and matched controls. Secondly, commercial microarray technology and next generation sequencing (NGS) will be employed to screen for all major HERVs and human exogenous retroviruses and to look for HERV sequence variants that may be associated with this disease.
This research study will involve collaborations with King’s College London, Maurice Wohl Clinical Neuroscience Institute. Post-mortem brain tissue will be obtained from MRC UK Neurodegenerative Disease Brain Bank Network following tissue transfer agreement which includes ethical approval.
The student will acquire extensive knowledge in the field of Virology and in a variety of Molecular Biology techniques (ie: qPCR, next generation sequencing and data analysis).
The student will receive training in relevant techniques/technologies and gain expertise in a number of key project planning and analytical research and subject specific skills. The student will also take part in the University Graduate School and Faculty Doctoral Research Development Programme (DRDP) including transferable skills (eg presentation skills, scientific writing and employability skills) which aid in their future career progression. The student will also be encouraged to join relevant learned societies, which provide excellent support for students in terms of training opportunities and meetings to disseminate and publish their research.
Please contact Dr Adele McCormick, [email protected].
5pm on 10 February 2017
Applications should be made to the Life Sciences MPhil/PhD programme and you should clearly state that you are applying for a Quintin Hogg Trust Scholarship and the Scholarship code (eg FST1) on your application.