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Identifying the mechanisms underlying the effect of neurotoxic spider venoms on the parasite, Fasciola hepatica


Project Description

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 or flukicides. There are a limited number of flukicides on the market and resistance to one of the most effective, triclabendazole, is widespread globally. The liver fluke life cycle relies on a mollusc intermediate host, Galba truncatula. Both G. truncatula and the extra-mammalian stages of the parasite are dependent on mild temperatures and rainfall. Liver fluke is predicted to become more widespread and prevalent as the climate changes. Farmers are becoming more dependent on the use of flukicides and concomitantly, anthelmintic resistance is becoming a major impediment to fluke control. There is no prospect of a commercial vaccine for control of fasciolosis appearing in the near future, so development of novel drugs is vital to help control disease.

The aim of this project is to test novel neurotoxins, derived from spider venom, on F. hepatica and to investigate the mechanisms underlying how these toxins exert their effect.

Advanced skills in recombinant protein production, in vitro toxicity assays, imaging and bioinformatics will be developed. The F. hepatica genome will be mined for gene families that are the targets for the toxins and their functionality established using gene silencing methods.

HOW TO APPLY
Applications should be made by emailing with a CV (including contact details of at least two academic (or other relevant) referees), and a covering letter – clearly stating your first choice project, and optionally 2nd and 3rd ranked projects, 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. Applications not meeting these criteria will be rejected.
In addition to the CV and covering letter, please email a completed copy of the Additional Details Form (Word document) to . A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

Informal enquiries may be made to:

Funding Notes

This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£15,009 for 2019-20). The PhD will start in October 2020. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. Please note, there are 2 stages to the application process.

References

Refugia and anthelmintic resistance: Concepts and challenges. Int J Parasitol Drugs Drug Resist. 2019 Aug; 10: 51–57. Published online 2019 May 17. doi: 10.1016/j.ijpddr.2019.05.001

A mechanistic hydro-epidemiological model of liver fluke risk. Journal of the Royal Society Interface (2018) 15(145): 20180072. doi: 10.1098/rsif.2018.0072.

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

In silico analyses of protein glycosylating genes in the helminth Fasciola hepatica (liver fluke) predict protein-linked glycan simplicity and reveal temporally-dynamic expression profiles. Sci Rep. 2018 Aug 3;8(1):11700. doi: 10.1038/s41598-018-29673-3.

A model to assess the efficacy of vaccines for control of liver fluke infection. Scientific Reports, 2016 Mar 24;6:23345. doi: 10.1038/srep23345

Gene duplication and polymorphism in the Fasciola hepatica genome reveals adaptation to the host environment and the capacity for rapid evolution. Genome Biol. 2015 Apr 3;16:71. doi: 10.1186/s13059-015-0632-2.

RNAi dynamics in Juvenile Fasciola spp. Liver flukes reveals the persistence of gene silencing in vitro. PLoS Negl Trop Dis. 2014 Sep 25;8(9):e3185. doi: 10.1371/journal.pntd.0003185.

Novel biopesticide based on spider venom protein shows no adverse effects on honeybees. Proc. R. Soc. B, 281, 20140619. http://dx.doi.org/10.1098/rspb.2014.0619

Demonstrating the potential of a novel spider venom based biopesticide for target-specific control of the small hive beetle, a serious pest of the European honey bee. J. Pest Science 2019, https://doi.org/10.1007/s10340-019-01143-3.

Stimulating Neoblast-Like Cell Proliferation in Juvenile Fasciola hepatica Supports Growth and Progression towards the Adult Phenotype In Vitro. 2016 PLoS Neglected Tropical Diseases 10(9).

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