A functioning immune system disables threats to health without causing autoimmunity. Gaining the ability to precisely control the immune response would revolutionise treatments for autoimmune conditions, cancer, transplant rejection and pathogenic infections. This has not been achieved due to the vast complexity of the immune system.
Pathogens such as some malaria-causing Plasmodium spp. parasites have co-evolved with the human immune system and can establish life-long apparently asymptomatic infections. Understanding how they regulate host immunity could provide a short cut to identifying novel immunoregulatory pathways that can be exploited to develop new medicines.
One emerging mechanism used by these pathogens are to display cell surface ligands that directly interact with host cell surface receptors to modulate the immune response. Using large scale extracellular protein interaction assays, we have identified direct interactions with host receptors for bacterial and parasite ligands for leukocyte receptors [1-5]. Importantly, we have found evidence that these very different pathogens have evolved to impinge on the same host receptors suggesting an evolutionary convergence on the same immunoregulatory pathways.
The aims of the PhD project will be to:
- Investigate the commonalities and differences in binding and immune signalling function of known bacterial and parasite ligands for host receptors using quantitative high throughput proteomics interaction assays and cell-based signalling assays.
- Using a systematic extracellular protein interaction assay and single cell genetic approaches, discover new direct interactions to reveal novel immunoregulatory pathways used by both Plasmodium spp. parasites and Streptococcus spp. bacteria.
The project will take advantage of a large panel (>630 proteins) of human leukocyte receptor ectodomains [3]: a new and exciting resource that now provides a simpler technical route to identifying host-pathogen interactions in a systematic and comprehensive manner.
You will have access to state-of-the-art capabilities at the University of York Biosciences Technology Facility (https://www.york.ac.uk/biology/technology-facility/) and join an active community of PhD students on the training programme which includes a seminar series, journal clubs and training courses.
Lab web sites: http://www.wright-lab.org/ and https://dralexmccarthy.wixsite.com/alexmccarthylab
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: https://www.dimen.org.uk/blog
Further information on the programme and how to apply can be found on our website: https://www.dimen.org.uk/how-to-apply
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