The Challenge: Fasciola hepatica is a zoonotic pathogen that causes fasciolosis in animals and humans. Control is precarious and in the absence of an effective vaccine reliant on a small portfolio of flukicides to which resistance is growing. More problematic is the fact that only one flukicide is effective against the migrating juvenile fluke which causes acute disease during its passage through the liver. We have compelling evidence that disease virulence and drug susceptibility are profoundly impacted by pathogen growth rate, but data on pathogen growth are not readily available and therefore are not used to guide forecasts on disease outbreaks and intensity. Accurate forecasts from environmental markers are needed to guide fluke treatment regimens. This project sets out to address this shortfall for liver fluke and identify new biomarkers to inform regional differences in zoonotic parasite disease risk.
Project Impetus: The project is founded on recent discoveries and state-of-the-art tool developments, including: (A) Tools–in vitro culture, functional genomics, phenotype screening and proteomics platforms for liver fluke; (B) Discoveries–identification of growth/development pathways that are common to both cancer and liver fluke stem cells and which govern pathogen growth rate/survival. We propose to use these new tools and resources for liver fluke to: probe the impacts of altered growth rate on pathogen biology and drug susceptibility; to use proteomic analyses of juvenile fluke displaying enhanced growth to identify protein biomarkers for enhanced growth/virulence; and, use these new biomarkers to inform regional differences in disease risk.
Overarching hypothesis: Enhanced virulence and therapy resistance in liver fluke are associated with rapid growth and a defined panel of protein biomarkers that can be used to identify regional differences and environmental drivers of disease intensity, thereby informing field-based pathogen control.
Aim 1 – The identification of pro-growth pathways in liver fluke (QUB). This aim will exploit state-of-the-art understanding from cancer cell biology and unique transcriptomic resources to identify the core signaling pathways involved.
Aim 2 – Functional genomics screens of genes associated with pro-growth pathways in liver fluke (QUB & BI). This aim will exploit the gene silencing platform developed for liver fluke at QUB and the screening capabilities of BI to identify genes that associate with faster pathogen growth/development, as well as therapy resistance.
Aim 3 – Identification of biomarkers of rapid growth that can inform regional variations in disease risk (AU). This aim will exploit state-of-the-art mass spectrometry platforms to identify protein markers for enhanced pathogen virulence/growth and therapy resistance in liver fluke. These biomarkers will be used to inform pathogen virulence and drug resistance across geographic regions where fasciolosis is endemic.
The Supervisor Team and Research Disciplines Encompassed by the Project: The project is multi-disciplinary and brings together a supervisor team across multiple distinct laboratories including: (i) the Maule lab (QUB) which has developed state-of-the-art tools for the in vitro maintenance and growth of liver fluke and where the student would undertake molecular biology studies on pathogen biology; (ii) the Morphew lab (Aberystwyth) which has pioneered the proteomic analysis of liver fluke and where the student would undertake proteomic studies on markers for altered growth; (iii) the Longley lab which investigates key drivers for cancer stem cell growth and proliferation and has made key discoveries on mechanisms that govern tumour growth rate (QUB), and; (iv) the Harrington parasite/pathogen screening lab in Boehringer Ingelheim that enables high throughput assessments of pathogen phenotype and drug impacts on pathogens, including liver fluke. The Hodgkinson lab will bring expertise in liver fluke genetics and ecology and will provide regional and clonal isolates of liver fluke with variable virulence.
Duration: 3.5 years full-time (or up to 7 years part-time)
Start Date: October 2023
How to apply: By 1 May 2023 all applications must be submitted online via: https://dap.qub.ac.uk/portal/user/u_login.php (Specify in the funding section that you wish to be considered for UKRI OneZoo funding). Please specify that you are applying for this particular project and name the supervisor.
You must also by 1 May 2023 send the following to [Email Address Removed] (title of the email must include the name of the host institution to which you are applying, e.g. Queen's University Belfast, and the surname of the principal supervisor):
If not successful in being shortlisted for this particular studentship you could be considered for other studentships within the OneZoo program.
It is expected that interviews will be held around the end of May 2023.
General Information:
Our transdisciplinary OneZoo CDT will equip the next generation of world-leading scientists with the skills and insight necessary to tackle current and future zoonotic threats. To design successful, innovative environmental prevention and control strategies, zoonotic drivers need to be understood through an integrated approach. As part of the OneZoo program you will build an in-depth understanding of the connectivity between key drivers of pathogen host shifts, spillover and onward transmission; exploring pathogen, environmental and human societal processes that can promote zoonotic disease and form the basis of integrated solutions. Our award-winning educators and experts in zoonotic diseases and environmental sciences, from Cardiff University, Aberystwyth University, Queen’s University Belfast, and the London School of Hygiene and Tropical Medicine, will work collectively, fostering creation of the OneZoo research community, and empowering students to develop their own training to acquire strong employability skills. This CDT offers an unprecedented level of diversity and transdisciplinarity.
Queen’s University: Research within the School of Biological Sciences contributes to the underlying biological mechanisms of life and disease, seeking to deliver new solutions with major economic, societal and environmental impact. Through our research-led teaching, we will inspire and train new generations of researchers, equipping our graduates with the skills and understanding needed to contribute to research, the knowledge-based economy and wider society. https://www.qub.ac.uk/schools/SchoolofBiologicalSciences/
Our reputation: Queen’s University research has been rated joint 1st= in the UK Research Excellence Framework for Agriculture, Veterinary and Food Science and 4th= in the UK for Health and Biomedical Sciences.
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