(Fully-funded MRC DiMeN DTP) Understanding autoimmunity: Why do B cells sometimes attack our tissues instead of protecting us from infections?

B cells are white blood cells part of the body's immune system that produce antibodies and protect us from infections. On rare occasions, B cells produce antibodies that attack tissues leading to autoimmune diseases. Chagas disease, a neglected tropical disease caused by Trypanosoma cruzi parasites, is the leading cause of infectious heart disease worldwide and the highest-impact parasitic disease in the Western Hemisphere. In response to T. cruzi infection, the immune system produces two kinds of antibodies: 1) against the parasite (protective), 2) against the heart (harmful). How this happens is poorly understood. 

The goal of this Project is to discover the signals that drive the immune system to target the heart during T. cruzi infection

For this, we have generated novel B-cell tetramers that allow us to isolate and study the molecular and functional characteristics of parasite- and heart-specific B cells. We also have access to a unique combination of:

• State-of-the-art facilities and multi-omics technologies
• Novel mouse models of bioluminescent-reporter T. cruzi infections
• A bank of Chagas disease patient samples

We will combine B-cell tetramers with flow cytometry, single-cell RNA sequencing, spatial transcriptomics, RNAscope, cutting-edge microscopy and recombinant antibodies to delineate molecular signatures, kinetics, tissue distribution and function of parasite- and heart-specific B cells in mice and humans. Running this study in both animal models and human samples will highly increase its translational value.

Despite affecting more than the estimated number of people suffering from Parkinson's disease or lupus globally, Chagas disease receives little attention from governments. No vaccines are available and drug treatments are limited and toxic. This research will generate foundational knowledge that will help us produce novel treatments to improve life quality not only of people suffering this neglected tropical disease, but also autoimmune diseases in general.

We provide an environment with the flexibility and resources required to excel in research while still being able to fulfil personal commitments and enjoy quality leisure time. Researchers in our team will be encouraged to visit different countries and laboratories and enrich themselves with the diversity of environments and people that our network provides. 

Webpages to our laboratories:

https://www.hyms.ac.uk/about/people/damian-perez-mazliah

http://www.wright-lab.org/

https://sbc.shef.ac.uk/team/mark/

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