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Host-parasite interactions: Protozoan parasites that effect host physiology and neurobiology and approaches for novel treatments

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  • Full or part time
    Dr G Mcconkey
  • Application Deadline
    Applications accepted all year round

Project Description

The interaction of human and animal hosts with pathogens is key to understanding effects on the host and measures for treatment. For example, the parasite Toxoplasma forms cysts in the brain and causes behavior changes yet the intricacies of the interplay with the neurons are not understood. Indeed, infected rodents lose their fear of cats (the definitive host). Other examples of host effects exist in the literature largely unexplained. The affect on neural circuitry has yet to be defined. Whereas, Plasmodium devastates the host physiology and only through understanding metabolic differences between the parasite and host can novel drugs and their targets be identified. The project is ideally situated within the University’s strong commitment to research in the areas of neurobiology and infectious biology.

The candidate will focus on host-parasite interactions of a protozoan parasite. Alterations in host physiology (such as neurotransmission with Toxoplasma infection) and how these can be exploited for drug targeting will be examined following on from RNA-seq findings. The candidate will examine metabolic consequences of infection and characterize effects of infection on genes and metabolites expressed. Ultimately, parasites with genes disrupted will be generated and evaluated to differentiate host and parasite derived factors in infection. Techniques will include recombinant proteins, biochemical assays, immunofluorescent microscopy, HPLC, qPCR, and Western blotting. Recombinant biology and parasite cultivation techniques will be involved.

References

1. MAGEED, S.N.*, CUNNINGHAM, F., HUNG, A.W., SILVESTRE, H.L., WEN, S., BLUNDELL, T.L., ABELL, C., & MCCONKEY, G.A. (2014). Pantothenic Acid Biosynthesis in the Parasite Toxoplasma gondii: a Target for Chemotherapy. Antimicrobial Agents & Chemother. 58:6345-53. *self-funded PhD student
2. MCCONKEY, G.A., MARTIN, H.L., BRISTOW, G. & WEBSTER, J.P. (2013). Toxoplasma brain infection and behaviour: location, location, location? Journal of Experimental Biology 216: 113-9.
3. WEBSTER, J.P., KAUSHIK, M.*, BRISTOW, G. & MCCONKEY, G.A. (2013). Toxoplasma gondii infection – from predation to schizophrenia - can animal behaviour help us understand human behaviour? Journal of Experimental Biology. 216:99-112. * PhD student
4. BEDINGFIELD, P.*, COWEN, D., ACKLAM, P., CUNNINGHAM, F., PARSONS, M., MCCONKEY, G., FISHWICK, C., JOHNSON, A. (2012) Factors influencing the specificity of inhibitor binding to the human and malaria parasite dihydroorotate dehydrogenases. Journal of Medicinal Chemistry 55(12):5841-50. * PhD student
5. PRANDOVSZKY, E., GASKELL, E.*, DUBEY, J. P., WEBSTER, J. P. & MCCONKEY, G.A. (2011). The neurotropic parasite Toxoplasma gondii increases dopamine metabolism. PLoS ONE. 6(9), e23866. * PhD student
6. FRITZSON, I.*, BEDINGFIELD, P.T.P.*, SUNDIN, A.P., MCCONKEY, G., NILSSON, U.J. (2011) N-Substituted salicylamides as selective malaria parasite dihydroorotate dehydrogenase inhibitors. MedChemComm 2, 597 895−898.

How good is research at University of Leeds in Biological Sciences?

FTE Category A staff submitted: 60.90

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