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Investigating the molecular and cellular basis of impaired vaccine responses in parasitic worm infection


   MRC DiMeN Doctoral Training Partnership

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  Dr J Hewitson, Dr Cecile Crosnier, Dr B Khatri  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Parasitic helminth infections afflict ~1/4 of the global population. Our studies have focused on schistosome parasites that infect >200 million people, 90% of whom live in sub-Saharan Africa. Individual schistosome worms can survive for many years within infected people, and this reflects the parasite’s ability to interfere with host immune responses [1]. Whilst this likely evolved to promote infection chronicity, it also causes immune suppression to bystander challenges including co-infections and vaccines. To achieve this, parasitic worms produce a variety of inhibitory molecules that interfere with host immunity. However, the identity of these molecules in schistosome infection and the mechanisms by which they modulate host immunity are not well understood.

In this project, you will investigate the molecular and cellular basis of schistosome-induced immune suppression, with a focus on vaccine-induced immune responses. As impaired immune responses are most strongly associated with chronic infection (i.e. in the presence of egg-laying adult worms), you will test the hypothesis that adult worms and/or eggs produce immunosuppressive proteins that modulate immune cell activation and vaccine responses. To do this, you will first identify worm and egg secreted proteins and utilise high-throughput methods of recombinant expression in mammalian cells [2], before testing the impact of these molecules using in vitro and in vivo immunological assays. This will focus on immune responses to both model antigens and following the human vaccine, BCG. Greater understanding of the molecular mechanisms by which schistosomes to establish chronic infection can lead to new anti-parasite strategies as well as the discovery of novel therapeutic candidates in the control of allergic and auto-immune conditions.

You will be supervised in York by two MRC funded researchers who take complementary approaches to investigate schistosome immune suppression (host immunological pathways and putative parasite immunomodulatory molecules). The project benefits greatly through collaboration with a third supervisor based at NIBSC (National Institute of Biological Standards and Control, UK) who is an expert in mouse models of BCG vaccination and tuberculosis. Together, this project will provide you with extensive training in multiple biochemical techniques and in vitro/in vivo immunology. The project will be suitable for a graduate in Biomedical Sciences, Biochemistry, Biology or related subjects with a strong interest and background knowledge of immunology and/or parasitology.

Project supervisors:

https://www.york.ac.uk/biology/research/infection-immunity/james-hewitson/

https://www.york.ac.uk/biology/our-staff/dr-cecile-crosnier/

https://www.nibsc.org/about_us/staff_profiles/dr_bhagwati_khatri.aspx

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 


Funding Notes

Studentships are fully funded by the Medical Research Council (MRC) for 4yrs. Funding will cover tuition fees, stipend and project costs. We also aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of full studentships to international applicants. Please read additional guidance here: https://www.dimen.org.uk/eligibility-criteria
Studentships commence: 1st October 2023
Good luck!

References

Maizels, R.M., H.H. Smits, and H.J. McSorley, Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules. Immunity, 2018. 49(5): p. 801-818. https://pubmed.ncbi.nlm.nih.gov/30462997/
Crosnier, C., et al., Screening of a Library of Recombinant Schistosoma mansoni Proteins With Sera From Murine and Human Controlled Infections Identifies Early Serological Markers. J Infect Dis, 2022. 225(8): p. 1435-1446. https://pubmed.ncbi.nlm.nih.gov/32524140/
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