Disentangling the role of beta-tubulin isotypes in the roundworm Ascaris in emergence of resistance to deworming drugs
This PhD project will combine parasitology with molecular biology and bioinformatics to investigate the role of beta-tubulin isotypes in emergence of resistance to deworming drugs in the roundworm Ascaris.
This PhD studentship has been generously funded by the Legacy of Mr Kenneth Longhurst. Funding will cover University registration fees at the UK/EU rate for three years and a stipend for three years at the UK Research Council National Minumum (£14553 per annum for 2017/18). In addition, funding includes bench fees to cover laboratory studies and conference attendance. As a condition of the funding, the PhD studentship must commence in October 2018.
This intestinal parasite infects ~800 million people globally, causing significant morbidity. A closely-related worm infects pigs worldwide, leading to decreased growth rates with impacts on food security. Current control of Ascaris is based on administration of deworming drugs (benzimidazoles) to preschool and school-aged children. Deworming is also an important method of intestinal worm control in pigs. There is growing concern that resistance to deworming drugs may develop in Ascaris. However, monitoring of human worm control programmes does not routinely employ drug resistance investigations. Studies on livestock roundworms revealed that resistance to benzimidazoles is associated with mutations in the beta-tubulin isotype 1 gene. 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 resistance to deworming drugs. This PhD will aim to address key gaps in our understanding of resistance in Ascaris. The PhD student will:
- Establish and test in vitro assays for detection of resistance to deworming drugs in Ascaris.
- Use bioinformatics approaches to identify beta-tubulin isotypes in the Ascaris genome and determine expression of these isotypes during Ascaris development.
- Determine the genetic variation of beta-tubulin isotypes in Ascaris isolates collected from different geographical locations and identify genetic changes potentially involved in resistance to deworming drugs.
- 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 detect 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 project will be supervised by Dr Martha Betson, Dr Arnoud van Vliet and Dr James La Course at Liverpool School of Tropical Medicine. 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.
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 20 August 2018.
How to apply
Please apply for this studentship through the Veterinary Medicine and Science PhD course page. 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.