Molecular and phenotypic monitoring of anthelmintic drug resistance in human helminthiases

Continued mass intestinal deworming programmes raise concerns of drug-resistance emerging.  Little is known of the molecular and phenotypic effects on worm populations under selection pressure affecting humans.  This PhD would develop/apply phenotypic and molecular-based laboratory and field tools to monitor drug-resistance alleles and drug efficacy in human gut-helminth populations to provide new data for models of control.

Where does the project lie on the Translational Pathway?

T2 – Human/Clinical Research, T3 – Evidence into Practice, T4 – Practice to Policy/Population

Expected Outputs

  • This project would generate the first extensive quantitative data on frequency of putative resistance alleles, genotypes and population structural changes under pressure from mass administration of anthelmintics in faecally-diagnosed helminths affecting humans.
  • The project would develop and optimise in vitro phenotype assay(s) for testing anthelmintic sensitivity in faecally-diagnosed helminths affecting humans.
  • The project would develop and optimise molecular assays to determine, during deworming programmes, population structural changes in helminths appropriate for application in well-resourced and low-resourced laboratory and field settings, to include and assess the development/application of probe-based (TaqMan) assays, pyrosequencing approaches, allele-specific LAMP and RPA assays.
  • The project would provide data to inform and guide mathematical models in developing strategies for rational and judicious use of the few existing anthelmintics and subsequent impact upon policy decisions/guides in drug usage and combinations.

 

Training Opportunities

The primary supervisor of this PhD project is also the Director of MSc Studies in Tropical Disease Biology, and can offer a range of additional training opportunities within and around the project focus.  Specific training can include modules/lectures/online resources, covering ‘Research Methods, ‘Applied Bioinformatics’, Molecular Biology’, Advanced Statistics’ and ‘Epidemiology’ to name but a few over the time course of the PhD.

 A student undertaking this PhD training will also engage in an ongoing, self-directed programme of training and professional development throughout their studies; reflecting on their skills and identifying training needs via a ‘Development Needs Analysis’ (DNA), which is reviewed annually as a key component of the student’s formal progress review.

LSTM provides a unique programme of training opportunities, events and seminars (updated each semester) to encourage students to meet other researchers from a wide range of specialities to grow their network. LSTM utilises innovative Technology Enhanced Learning initiatives to ensure that students working in the field are able to interact as fully as possible with training sessions. The full catalogue of MSc modules delivered at LSTM are available for study and students can attend lectures and seminars.

Skills Required

The student would have achieved at least a high-class BSc degree in a biological science with good content/understanding and/or additional experience of molecular biology and/or biochemistry and genetics.   A knowledge of organism culture and bioinformatics is desirable but not essential.  Experience overseas in resource-poor settings is desirable but again not essential.

Key Publications associated with this project

Corrado Minetti, E. James LaCourse*, Lisa Reimer & J. Russell Stothard.  (2016). Focusing nucleic acid-based molecular diagnostics and Xenomonitoring approaches for human Helminthiases amenable to preventive chemotherapy.  Open Parasitology (in Press).

Cwiklinski, Krystyna, Dalton, John Pius, Dufresne, Philippe J, LaCourse, James, Williams, Diana Jl, Hodgkinson, Jane and Paterson, Steve (2015) 'The Fasciola hepatica genome: gene duplication and polymorphism reveals adaptation to the host environment and the capacity for rapid evolution.'. Genome Biology, Vol 16, e71.

Alhassan, Andy, Makepeace, Benjamin L., LaCourse, James, Osei-Atweneboana, Mike Y. and Carlow, Clotilde K. S. (2014) 'A Simple Isothermal DNA Amplification Method to Screen Black Flies for Onchocerca volvulus Infection'. PLoS ONE, Vol 9, Issue 10, e108927.

Armstrong SD, Xia D, Bah GS, Krishna R, Ngangyung HF, LaCourse EJ, McSorley HJ, Kengne-Ouafo JA, Chounna-Ndongmo PW, Wanji S, Enyong PA, Taylor DW, Blaxter ML, Wastling JM, Tanya VN, Makepeace BL.

Mol Cell Proteomics. 2016 Aug;15(8):2554-75. doi: 10.1074/mcp.M115.055640. Epub 2016 May 25

Cwiklinski, Krystyna, Allen, Katherine, LaCourse, James, Williams, Diana J., Paterson, Steve and Hodgkinson, Jane E. (2015) 'Characterisation of a novel panel of polymorphic microsatellite loci for the liver fluke, Fasciola hepatica, using a next generation sequencing approach'. Infection Genetics and Evolution, Vol 32, pp. 298-304.

LSTM Themes and Topics – Key Words

Resistance Research and Management. AND  Neglected Tropical Diseases

The call for applications for the 2020-21 round of studentships is now OPEN. Deadline for receipt of complete application 23:59 13th February 2020

Further information on the programme and application process can be found here