Supervisors: Prof. Neil A. Mabbott, Dr Liam Morrison
Project Description:
An enthusiastic student with experience in parasitology or immunology is sought for an exciting four year Ph.D. studentship which aims to study the effects of helminth co-infections on susceptibility to African trypanosomiasis.
African trypanosomes are extracellular protozoan parasites that are transmitted between mammals by tsetse flies. These parasites cause chronic infections in the mammalian bloodstream (African trypanosomiasis) and inflict substantial economic strains on African livestock industries. Much of our understanding of the pathogenesis of African trypanosomiasis is derived from experimental transmissions of individual parasite strains to mice or cattle. However, in the field it is increasingly apparent that pathogen co-infections within the same host species are common. For example, chronic infections with pathogens including malarial parasites, gastrointestinal helminths, Mycobacterium tuberculosis and viruses such as HIV may affect up to a third of the human population in some developing countries. Increasing evidence shows that co-infection with these pathogens can alter susceptibility to infection by other important pathogens, and/or influence vaccine efficacy by affecting host immune function. Co-infection with some pathogens may also hinder the accuracy of certain diagnostic tests against other pathogens.
Studies in mice have shown that the host’s immune response to a gastrointestinal helminth infection can alter susceptibility to co-infection with a variety of other bacterial and viral pathogens including Salmonella enterica serovar Typhimurium, Citrobacter rodentium and norovirus. However, although livestock species such cattle and buffalo are regularly exposed to gastrointestinal helminth parasites, nothing is known of the effects that co-infection with these pathogens may have on susceptibility to infection with African trypanosomes. Therefore, the first major aim of this project is to test the hypothesis that co-infection with gastrointestinal helminths significantly influences disease susceptibility and pathogenesis following infection with African trypanosomes.
During African trypanosome infections the host’s macrophages are stimulated to help clear the parasites. However, the over-reaction of these pro-inflammatory macrophages to the trypanosome infection causes significant immunopathology in host tissues and the suppression of antigen-specific immunity. Conversely, during helminth infections the macrophages adopt an alternatively-activated phenotype that plays an important role in immune regulation and repairing the tissue damage caused. Whether African trypanosome infections can influence macrophage polarity and function in response to helminths is unknown. Therefore, the second major aim of this project is to test the hypothesis that the potent pro-inflammatory macrophage response that is induced in African trypanosome infections negatively impacts on the ability of macrophages to repair the damage caused by helminths in the intestine.
No vaccines are available to block African trypanosome infections, and the development of resistance to commonly used trypanocidal drugs is a constant issue. A thorough understanding the factors that influence susceptibility to African trypanosomiasis will help reveal novel targets for effective intervention and prevention.
This project will utilize the mouse gastrointestinal helminth and African trypanosome infection models that are available in the supervisors’ laboratories. The project brings together several important biological disciplines, including parasitology, mucosal immunology and bio-imaging. Thus, the student will be provided with many excellent training opportunities in the following important transferable skills: in vivo biology; state-of-the-art bio-imaging; cell culture; transcriptomics.
For further information please contact Prof Neil Mabbott or Dr Liam Morrison.
Useful reading:
Beschin A, van den Abbeele J, De Baetselier P and Pays E (2014) African trypanosome control in the insect vector and mammalian host. Trends in Parasitology 30:538-547.
Morrison LJ, Vezza L, Rowan T and Hope JC (2016) Animal African trypanosomiasis: Time to increase focus on clinically relevant parasite and host species. Trends in Parasitology 32:559-607.
Reynolds LA, Redpath SA, Yurist-Doutsch S, Gill N, Brown EM, van der Heijden J, Brosschot TP, Han J, Marshall NC, Woodward SE, Valdez Y, Borchers CH, Perona-Wright G, Finlay BB. (2017) Enteric helminths promote Salmonella coinfection by altering the intestinal microbiome. Journal of Infectious Disease 215:1245-1254.
If you wish to apply for this project, please check this link and send your application to this email.
