Dr R McCulloch, Dr L Morrison
No more applications being accepted
Funded PhD Project (European/UK Students Only)
About the Project
MRC DTP in Precision Medicine
Up to 26 fully funded studentship positions are available across the University of Glasgow and Edinburgh. Our next intake will be for PhD projects commencing September 2017.
The Precision Medicine Doctoral Training Programme (DTP) offers PhD with Integrated Study studentships funded by the Medical Research Council (MRC), The University of Edinburgh and the University of Glasgow. Hosted by the University of Edinburgh in collaboration with the University of Glasgow and the Karolinska Institute, this prestigious programme provides PhD research training alongside taught courses over four years of study and welcomed its first cohort of students in September 2016.
This new Doctoral Training Programme focuses on training PhD students in key MRC skills priorities in quantitative skills (mathematics, statistics, computation, and developing digital excellence) as applied to variety of data sources (from ‘omics’ to health records), and interdisciplinary skills including imaging and stratified medicine.
Supervisors
Dr Richard McCulloch - [Email Address Removed]
Dr Liam Morrison - [Email Address Removed]
Dr Christina Cobbold - [Email Address Removed]
Abstract
Diversity is fundamental to biological processes at all scales. One area in which measuring diversity is critical, and where quantification will have wide application, is in host-pathogen interaction. To counter host immunity, most pathogens depend upon expressing diverse antigens for survival and transmission. African trypanosomes are an exemplar of pathogen immune evasion by antigenic variation (AV). In Trypanosoma brucei switches in the composition of a protective ‘coat’ composed of Variant Surface Glycoprotein (VSGs) is driven by recombinatorial gene rearrangements, and VSG diversity is central to this process. Despite recent advances, our knowledge of trypanosome VSG diversity remains limited. First, VSG expression across infections has to date been assessed by cloning and Illumina sequencing of VSG mRNAs, potentially underestimating the extent of VSG diversity and posing problems for assembly of VSG transcripts. Second, only VSG mRNAs expressed during infections have been examined; no experiments have examined the VSG genomic archive across infections. Finally, there has been no attempt to apply mathematical approaches to measure T. brucei VSG diversity during infections. This project will address all these issues:
1. Sample parasite RNA and genomic DNA at multiple time-points during T. brucei infections and evaluate dynamics of expressed VSG diversity and genomic changes, using both Pacific Biosystems (PacBio) and Illumina approaches.
2. Develop bioinformatics tools to assemble and identify the expressed VSGs and measure their abundance, and to assemble the VSG archive at different times in the infection.
3. Quantify VSG mRNA and genomic diversity through the development and application of appropriate mathematical models.
Funding Notes
Details on 'How to Apply' are available here: http://www.gla.ac.uk/colleges/mvls/graduateschool/precisionmedicine/howtoapply/
MRC DTP in Precision Medicine website: http://www.gla.ac.uk/colleges/mvls/graduateschool/precisionmedicine/