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Anti-Cancer Drugs for Parasite Control


   School of Biological Sciences

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  Prof A Maule, Dr L Atkinson  No more applications being accepted  Competition Funded PhD Project (UK Students Only)

About the Project

Stem cells play a central role in many cancers and successful treatments need to target the associated cancer stem cells to prevent disease progression and/or regrowth. There is now growing evidence that stem cells of selected parasites play a key role in the establishment and maintenance of parasite infections, also driving pathogen virulence. 

We have established a new programme of work based on the hypothesis that ‘the dysregulation of parasite stem cells is an effective strategy for parasite control’. A major facet of current cancer research focuses on understanding the biology of cancer stem cells to inform new chemotherapeutic treatments and improve outcomes. Many stem cell effectors are common across eukaryotes, meaning that stem cells from diverse organisms often express similar cohorts of genes/proteins. This raises the possibility that anti-cancer drugs (or related compounds generated during cancer drug development) could be selectively toxic to parasite stem cells and, therefore, could be re-purposed for parasite control. We have established an in vitro culture and functional genomics platform for juvenile liver fluke (Fasciola hepatica), one of the most pathogenic parasites of livestock animals and a neglected tropical disease of humans. Control of this parasite is a significant challenge due to the absence of a vaccine and its growing resistance to flukicides. We have found that its growth and establishment within the host is driven by rapid stem cell proliferation and differentiation and that dysregulation of fluke stem cells (either by irradiation or gene silencing of stem cell effectors – both of which selectively disrupt fluke stem cells) undermines growth and dramatically increases drug susceptibility, even in drug-resistant isolates. These findings encourage efforts to exploit the resources generated through decades of cancer therapy research for parasite treatment.

This project will exploit new transcriptomic datasets to identify stem cell effectors in liver fluke and validate their utility as new parasite control targets through two main aims: (1) Characterisation of the role of selected stem cell effectors by (a) localising their expression and (b) analysing their function using gene silencing (RNAi) to see if they play a key role in parasite growth/development during culture in the laboratory. (2) The testing of selected anti-cancer drugs (provided by Boehringer Ingelheim) known to act on stem cell targets that are common to both human cancer stem cells and liver fluke stem cells. The work will identify new opportunities for parasite control through the repurposing of cancer therapeutics.

Start Date: 1 October 2022

Duration: 3 years

How to apply: Applications must be submitted via: https://dap.qub.ac.uk/portal/user/u_login.php

Skills/experience required: Wet laboratory experience a must; some experience of molecular biology methods and/or bioinformatics a bonus.

Note: This project is in competition for DfE funding with a number of other projects. A selection process will determine the strongest candidates across the range of projects, who may then be offered funding for their chosen project.


Funding Notes

Candidates must hold a UK 2.1 Bachelor's degree or qualifications considered to be equivalent by the University.
Candidates must also be normally resident in the UK for the three year period prior to 1 October 2022. For non-EU nationals, the main purpose of residence must not have been to receive full-time education. Non-UK or Irish nationals must also have pre-settled or settled status (EU nationals) or settled status (non-EU nationals).
Full eligibility criteria: https://www.economy-ni.gov.uk/sites/default/files/publications/economy/Postgraduate-studentships-terms-and-conditions.pdf
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