This PhD project will exploit molecular and multi-omics techniques to interrogate uncharacterised aspects of parasitic nematode endocannabinoid signalling in Strongyloides species. The fundamental knowledge generated by this project will underpin drug target discovery efforts for parasite control.
Neglected Tropical Diseases (NTDs) caused by parasitic nematodes (PNs) inflict a devastating burden of disease on the world’s poorest people. Emergence of drug resistance, and shortfalls in available treatment options for key PN NTDs, magnify an urgent need for novel drug development pipelines to accelerate sustainable control approaches. The ongoing improvement of PN bioinformatics resources alongside recent genome-editing advances in Strongyloides parasites present an opportunity to drive novel drug target identification and validation though technology-driven research. Neuromuscular signalling governs key aspects of nematode biology and is the primary target for frontline anthelmintics, however key facets of nematode neurosignalling remain uncharacterised. Endocannabinoid (EC) signalling is implicated in a diverse range of neurological processes in vertebrates but has not been widely studied in the context of PN neurobiology. Available data suggest that nematodes possess nematode-specific EC-receptors that are conserved pan-phylum, and in therapeutically relevant nematode life-stages. The nematode EC signalling system therefore presents a unique, unexploited and potentially druggable system for novel chemotherapeutic control of PNs.
This PhD project will exploit molecular methods (immunolocalization, in situ hybridization, qPCR, transcriptomics) and advanced functional genomics approaches (RNAi and CRISPR) in the mammalian PN Strongyloides ratti to address the biological role(s) and importance of EC signalling in: (i) host-finding and invasion, (ii) the establishment and maintenance of infection, and (iii) parasite migration through host tissues. The data generated during this project will contribute novel fundamental knowledge and underpin drug target discovery efforts in PNs.
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: Molecular biology experience and/or training in bioinformatics and functional genomics are desirable, but are not essential. Training will be provided as necessary during the project.
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.