Understanding pharmacology to control liver fluke parasites

Fasciolosis is a global foodborne disease that infects both grazing animals and humans with increasing incidence through climate change and continued poor control management. The causative agents are Fasciola hepatica (temperate liver fluke) and F. gigantica (tropical liver fluke). F. hepatica has been identified is as a major risk to global food security, causing economic losses of over US$ 3 billion per annum to livestock through mortality, reduction in host fecundity, susceptibility to other infections, decrease in milk and meat production, and condemnation of livers. F. hepatica control, in the continued failure to produce commercial vaccines, is dominated by chemotherapy.

The main drug of choice for F. hepatica control is the pro-drug Triclabendazole (TCBZ). Pro-drugs require metabolic activation by the host’s liver in order to be active against a target parasite. Parasitic worms such as F. hepatica, damage the host’s liver, which we predict will negatively impact on the pharmacokinetic properties of the TCBZ anthelmintic. This PhD training programme will explore not only this factor but also dietary factors and the effect of simultaneous infections with more than one parasite species within the host, that impinge on the pharmacokinetics of pro-drugs and consequently on drug efficacy. The project aims to deliver new information to veterinarians/doctors to distinguish between drug failure and parasitic drug resistance.
The project will bring together four disciplines in order to provide modern research training in applied biology:
1) Molecular parasitology
2) Cell Biology
3) Ruminant microbiology
4) Ruminant nutrition

The successful student will be supervised by Dr Neil MacKintosh and work within the internationally recognised parasitology and ruminant nutrition groups of Professors Peter Brophy and Jamie Newbold as part of a unique collaboration in the Institute of Biological, Environmental and Rural Sciences, Aberystwyth. The student will receive research training in explant culturing, proteomics and rumen simulation, as well as other molecular and wet laboratory techniques.

This PhD programme builds upon other recent successful BBSRC, Pfizer and UK Levy Board funded F. hepatica PhD training programmes within the group (see Morphew et al. Molecular & Cellular Proteomics 6, 963-972; Chemale et al. Journal of Proteome Research 9, 4940-4951; Morphew et al. PLoS Neglected Tropical Diseases 5(1): e937; La Course et al. PLoS Neglected Tropical Diseases 6(5): e1666 and Brophy et al. Parasitology 139 (9), 1205-1217).

The project is especially suited to graduates in Pharmacology, Biology, Biochemistry, Veterinary or Animal Sciences requiring advanced research training in molecular parasitology and/or drug metabolism.

Candidates should have (or expect to achieve) a First Class or Upper second class honours degree and/or a masters degree
(or equivalent) in a relevant subject."

We encourage prospective candidates to contact the lead supervisor Dr Neil Mackintosh [Email Address Removed]; 01970 622949;
http://www.aber.ac.uk/en/ibers/staff/staff profiles/nnm08/

http://www.aber.ac.uk/en/ibers/opportunities-@-ibers/