Investigating the Neuro-Immune axis of African trypanosomiasis
Dr J Worthington
Dr L Jackson-Jones
Dr N Dawson
Dr M Urbaniak
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
A multi-disciplinary PhD project investigating the immune and neurological response to sleeping sickness is available within the Division of Biomedical and Life Sciences at Lancaster University. If successful you will join a world leading supervisory team including Immunologists Dr John Worthington and Dr Lucy Jackson-Jones, Neuroscientist Dr Neil Dawson and Parasitologist Dr Mick Urbaniak (supervisor research profiles available here: https://www.lancaster.ac.uk/health-and-medicine/about-us/people/). You will be at the forefront of current research into the Neuro-Immune axis and join a dynamic post-graduate research community.
The African trypanosome, a parasite that causes sleeping sickness, is able to infect humans and survive by evading the innate and acquired immune system. During the second stage of infection, the parasites cross the blood brain barrier (BBB) and enter the brain causing severe neurological disturbances. Neurological disturbances, including hallucinations and disturbances in sleep, often occur prior to brain penetration, but the mechanisms are largely unknown. We currently have little understanding of how trypanosomes affect brain function or how they perturb the immune system. However, our recent data suggest that disturbances in the Neuro-Immune axis, the link between the brain and the immune system, may be key.
Our initial work on a mouse infection model has found that the parasites localised to the adipose tissue and gut from the early stages of infection. We have recently shown that this leads to enlargement of the omentum, a specialised adipose tissue that contains small clusters of immune cells, and a massive expansion of the omental immune cell population. As the intestinal epithelial immune response drives inflammation along the gut-brain axis, and the omentum is important in host protection following intestinal-epithelial breakdown, these results provide a potential link between infection, the immune response and perturbed brain function in the early stages of trypanosomiasis infection
In this interdisciplinary project you will develop our understanding of how the immune system responds to parasite infections, and explore the link between immune activation and alterations in brain function and behaviour. Using an established in vivo model, you will explore how parasite infection influences the intestinal epithelial immune response and impacts on the activation of the omentum. You will characterise how the immune response contributes to the impact of trypanosomiasis infection on sleep and other behaviours in the translational model, and investigate the mechanisms by which this impact can be reduced using both in vivo and in vitro approaches.
During this 3 year PhD project you will gain broad expertise in disease research with unique, specialist training in trypanosome biology, immunology, preclinical in vivo models and behavioural analysis. You will develop a broad range of technical expertise including multi-parameter flow cytometry, confocal microscopy, primary cell isolation, microbial analysis, immunohistochemistry, qPCR, cell culture, preclinical behavioural and cognitive testing and brain imaging. Throughout your PhD you will also develop a range of transferable skills including data analysis, scientific writing and effective communication skills.
Lancaster University was named University of the Year by The Times and The Sunday Times Good University Guide 2018 and maintains a top 10 rank in all three major UK University league tables (The Times/Sunday Times, the Guardian and the Complete University guide). The Faculty of Health and Medicine was ranked joint 1st for research environment in the Allied Health Professions Research Excellence Framework 2014.
For informal enquiries related to this project please contact John Worthington: [Email Address Removed] or Lucy Jackson-Jones: [Email Address Removed]
Applications should be made directly to John Worthington: [Email Address Removed] or Lucy Jackson-Jones: [Email Address Removed] and should include:
CV (max 2 A4 sides), including details of two academic references
A cover letter outlining your qualifications and interest in the studentship (max 2 A4 sides)