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

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.