Dr M Betson, Dr Arnoud Van Vliet
No more applications being accepted
Funded PhD Project (European/UK Students Only)
About the Project
The neglected tropical infection Ascaris lumbricoides is a worm parasite which infects ~800 million people globally, particularly in low and middle income countries. It can cause significant morbidity and contributes 1.2 million disability adjusted life years to the global burden of disease. The intestinal worm A. suum is very closely-related to A. lumbricoides, and infects pigs and humans worldwide. Infections in pigs can lead to decreased food utilisation and growth rates with impacts on food security.
To date control of Ascaris has been dominated by preventive chemotherapy (PC): regular administration of benzimidazole (BZ) deworming drugs to preschool and school-aged children. The World Health Organisation (WHO) aims to reach 75% coverage of preschool and school-aged children at risk by 2020. Recently, there has been increasing focus on eliminating transmission of Ascaris and other intestinal worms with two ongoing studies investigating the feasibility of interrupting transmission using PC. Deworming using BZs is also an important method of intestinal worm control in pigs. With the scale-up of PC in humans and the reliance on a single drug class for worm control in pigs, there is growing concern that anthelmintic resistance may develop. Worryingly, reduced efficacy of BZ against human Ascaris infections has recently been reported in Rwanda.
Monitoring of human worm control programmes does not routinely employ drug resistance investigations unless clinical efficacy reduction is suspected. Furthermore, the existing faecal egg count reduction-based protocol for detection of reduced efficacy is insensitive and prone to confounding. Studies in livestock roundworms revealed that resistance to BZs is associated with single nucleotide polymorphisms (SNPs) at three codon positions in the beta-tubulin isotype 1 gene. Molecular methods for detection of these SNPs in Ascaris beta-tubulin isotype 1 have been developed but have yet to be widely applied alongside drug efficacy follow-up studies. To complicate matters, there are at least nine beta-tubulin isotypes in Ascaris, only four of which have been characterised, and it is unclear which one(s) may be involved in BZ resistance.
This PhD will aim to address key knowledge gaps in the field. The PhD student will:
1) Establish and test in vitro assays for detection of resistance to deworming drugs in Ascaris, using A. suum as a model.
2) Use bioinformatics approaches to identify beta-tubulin isotypes in the Ascaris genome and determine expression of these isotypes during Ascaris development.
3) Determine the genetic variation of beta-tubulin isotypes in A. lumbricoides and A. suum isolates collected from different geographical locations and identify genetic changes potentially involved in resistance to deworming drugs.
4) Develop molecular assays to detect SNPs associated with Ascaris beta-tubulin isotypes and apply these to Ascaris-positive faecal samples collected pre- and post-deworming treatment.
The enhanced understanding of beta-tubulin isotypes in Ascaris and the availability of new tools to monitor resistance resulting from this project will enable improved monitoring of resistance in Ascaris control programmes, allowing early detection of resistance and the adoption of alternative control strategies. This will ultimately result in improved public health in endemic areas. Project outputs can also be adopted for Ascaris resistance monitoring on pig farms, leading to improvements in production and food security, especially important given the increased global reliance on pork as protein source.
This project will be supervised by Dr Martha Betson (https://www.surrey.ac.uk/people/martha-betson), Dr Arnoud van Vliet (https://www.surrey.ac.uk/people/arnoud-van-vliet) and Dr James La Course at Liverpool School of Tropical Medicine (https://www.lstmed.ac.uk/about/people/dr-james-lacourse). Training in parasitology, molecular biology and bioinformatics will be provided by the supervisory team. The student will be strongly encouraged to participate in workshops and networking opportunities run by the Researcher Development Programme and to present their research at internal and external conferences.
How to Apply:
Please apply for this PhD through the School of Veterinary Medicine PhD applications portal https://www.surrey.ac.uk/postgraduate/veterinary-medicine-and-science-phd (click on the “Apply” tab). Applicants are invited to contact Dr Betson to discuss the project informally prior to making an application. Applicants are required to hold an undergraduate degree in Biological Sciences or a related subject. A Masters degree in a biology-related subject is desirable. Experience in molecular biology, bioinformatics and/or parasitology is desirable but not essential. It is anticipated that interviews will take place in the week commencing 20th August.
Funding Notes
This PhD studentship has been generously funded by the Legacy of Mr Kenneth Longhurst. Funding will cover University fees at the UK/EU rate for three years and a stipend for three years at RCUK levels. In addition, funding includes bench fees to a value of £18000 over the three years to cover laboratory studies and conference attendance. For further information see: https://www.surrey.ac.uk/postgraduate/veterinary-medicine-and-science-phd (click on the Fees and Funding tab). As a condition of the funding, the PhD studentship must commence in October 2018.
References
1) Jourdan et al. Lancet 391, 252-265 (2018)
2) Roespstorff et al. Vet Parasitol 180, 72-81 (2011)
3) Int J Parasitol Drugs Drug Resist 4, 164-184 (2014)
4) Betson et al. J Infect Dis 210, 932-941 (2014)
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