About the Project
ALS is a rapidly progressive, incurable and fatal disease that causes the degeneration of motor neurons (MNs) and consequent generalized paralysis. The molecular causes of the disease remain unknown, but genetic findings have implicated RNA processing as a potential mechanism leading to disease. The UCL Institute of Neurology, a leading clinical center in the UK, leads a comprehensive research program to test this hypothesis.
As part of a collaboration between the UCL Institute of Neurology and UCL Genetics Institute, we investigate this hypothesis using a range of models, including iPS cell lines and mice. New technologies, such as RNA-sequencing, can now be used to provide a genome-wide assessment of the transcriptome in these experimental models.
Our expectation is that the combination of quantitative data from multiple sources can provide novel clues into disease aetiology. However, this integrative analysis is a challenging computational and statistical task. During this PhD, the student will work on computational biology questions and large scale transcriptome sequencing datasets in the research group of Dr Plagnol, in collaboration with the clinical and cell biology teams led by Drs Pietro Fratta and Adrian Isaacs. The project will provide an opportunity to explore the use of deep learning techniques in the field of computational biology and develop classifiers for meaningful questions associated with splicing mechanisms.
The ideal student would have a background in computer science, statistics, or potentially biology with a strong interest in computational work. Prior experience in programming (in particular R) and/or high throughput DNA sequencing analysis is welcome but not necessary. If desired, there are opportunities to teach as part of this PhD, although there is no expectation. This 3 year fully funded PhD, including consumables, is expected to start in September 2017 but could potentially start as early as February 2017.
Relevant references:
- Mizielinska et al, C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins, Science 2014
- Sibley et al, Recursive splicing in long vertebrate genes, Nature 2015
- Humphrey et al, Quantitative analysis of cryptic splicing associated with TDP-43 depletion, BioRxiv, 2016
Funding Notes
This project, funded by the MND, has a core computational focus but will also draw from the wide array of expertise in place at UCL. Candidates should be from the UK/EU only. A tax-free living stipend of £17,000 in Year 1, £17,500 in Year 2 and £17,500 in Year 3 will be provided to the successful candidate.
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