The parasite, Fasciola hepatica (common liver fluke), is a significant cause of disease in ruminants and is a major constraint on livestock production globally. Control of liver fluke relies almost exclusively on the use of specific veterinary medicines, known as flukicides. There are a limited number of flukicides on the market and resistance to one of the most effective, triclabendazole, is widespread. The liver fluke life has a complex cycle that relies on a mollusc intermediate host, Galba truncatula and has other stages in the environment that can survive on pasture. Liver fluke is predicted to become more widespread and prevalent as the climate changes. As a result, farmers will become more dependent on the use of flukicides and drug resistance will become a major impediment to effective control of fasciolosis. This is compounded by the lack of a commercial vaccine. To ensure the sustainability of liver fluke control and maintain the health and welfare of sheep and cattle development there is a need to develop novel drugs.
Toxins from spider venoms have been shown to act on the nervous system of insect pests, specifically on the insect ion channels (eg as neurotoxins). The aim of this project is to use a newly developed parasite culture system for F. hepatica to test these novel neurotoxins derived from spider venom and explore their effect on liver flukes. This assay will determine their effect on immature, juvenile F. hepatica, the most pathogenic developmental stage of the parasite. We also aim to predict the 3D structure of these neurotoxic proteins and to investigate the mechanisms underlying how these toxins exert their effect.
Advanced skills in recombinant protein production and protein modelling, in vitro toxicity assays, imaging and bioinformatics will be developed. The targets for the toxins and their functionality will be established.
HOW TO APPLY
Applications should be made by emailing firstname.lastname@example.org with:
· a CV (including contact details of at least two academic (or other relevant) referees);
· a covering letter – clearly stating your first choice project, and optionally 2nd ranked project, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University;
· copies of your relevant undergraduate degree transcripts and certificates;
· a copy of your IELTS or TOEFL English language certificate (where required);
· a copy of your passport (photo page).
A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT https://www.nld-dtp.org.uk/how-apply. Applications not meeting these criteria may be rejected.
In addition to the above items, please email a completed copy of the Additional Details Form (as a Word document) to email@example.com. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.
Informal enquiries may be made to firstname.lastname@example.org
The deadline for all applications is 12noon on Monday 9th January 2023.
Open to students worldwide
Clonal amplification of Fasciola hepatica in Galba truncatula: within and between isolate variation of triclabendazole-susceptible and –resistant clones. Parasites and Vectors (2018) 11:363 doi:10.1186/s13071-018-2952-z.
A major locus, dominantly inherited, confers triclabendazole resistance in Fasciola hepatica
PLOS Pathogens (2022) submitted, under review.
The insecticidal activity of recombinant nemertide toxin α-1 from Lineus longissimus towards pests and beneficial species.(2021) Toxicon, 79-86 https://doi.org/10.1016/j.toxicon.2021.04.003.
Critical assessment of approaches for molecular docking to elucidate associations of HLA alleles with adverse drug reactions; Molecular immunology 101, 488-499.
RNA interference dynamics in juvenile Fasciola hepatica are altered during in vitro growth and development. Int J Parasitol Drugs Drug Resist (2020) 14:46-55. doi: 10.1016/j.ijpddr.2020.08.004. Epub 2020 Aug 19.