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Spatio-temporal dynamics of insulitis in human type 1 diabetes

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  • Full or part time
    Prof K Tsaneva-Atanasova
  • Application Deadline
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  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

This project is one of a number which are funded within the Carlota Palmer PhD programme. This four-year programme, run under the auspices of the Centre for Biomedical Modelling and Analysis, will commence in September 2016. The studentships will provide funding for a stipend (currently £16,165 per annum), research costs and UK/EU tuition fees for four years. Further details can be found here: http://www.exeter.ac.uk/bma/phd/

Location: Streatham Campus, University of Exeter, EX4 4QJ

Academic Supervisors: Prof Krasimira Tsaneva-Atanasova, Mathematics, University of Exeter, Professor Noel Morgan, Medical School, University of Exeter

Type 1 diabetes is a chronic autoimmune disease characterised by the selective destruction of pancreatic beta cells. The disease, which currently has no cure, affects around 400000 people in the UK, and is the more common form of diabetes in children. This requires life-long insulin administration and is associated with a significant reduction in life expectancy and quality of life.

This project will investigate the spatio-temporal dynamics of insulitis, the process by which immune cells invade the pancreas and kill the beta cells. This will be achieved through a combination of mathematical models and experiments using human tissue.

Heavily implicated as the main cause of type 1 diabetes are CD8+ T-lymphocytes, which are thought to be directly responsible for beta cell death. Other immune cells, such as CD4+ T-cells, B-lymphocytes and macrophages are also present during insulitis, although their roles are less well understood. Novel results from Morgan’s lab have identified two phenotypes of the disease: an aggressive form characterised by higher numbers of B-lymphocytes and a less aggressive phenotype involving fewer B-lymphocytes. This project will focus on the role of communication between the different immune cell subtypes to reveal how this results in a coordinated attack on the beta cells.

The mathematical models will be based on formulations developed recently in Exeter and take into account biological variability within the human pancreas. Previous modelling approaches have ignored the important spatial aspects of the disease progression, together with its inherent heterogeneity. The proposed framework overcomes this by describing the behaviour of individual cells as they move around the pancreas and interact with other cells. As such, the project will involve a significant number of simulations to be performed in an appropriate programming environment.

To validate the models and test in-silico generated hypotheses, an important component will be the collection of data from experiments using for example antibody staining of human tissue samples to identify relevant cells within the pancreas. In Exeter, we have access to around 75% of the world’s total human samples through the Exeter Archival Diabetes Biobank, tissue from the US Juvenile Diabetes Research Foundation Network for Pancreatic Organ Donors and pancreatic biopsy material from Norway’s DiViD study. Using experimental results, the models will be modified and improved in an iterative manner. Ultimately, the aim of the project is to use the modelling environment to identify new therapeutic avenues for targetted treatment of the disease.

Entry requirements:

Applicants should have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science or technology. Applicants with a Lower Second Class degree will be considered if they also have Master’s degree or have significant relevant non-academic experience. If English is not your first language you will need to have achieved at least 6.5 in IELTS (and no less than 6.0 in any section) by the start of the project (alternative tests may be acceptable, see http://www.exeter.ac.uk/postgraduate/apply/english/).

Funding Notes

£16,165 per annum plus UK/EU fees for eligible students (2015-16 rates)

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