Resolving developmental changes in transcript isoform usage in the liver fluke Fasciola hepatica
Supervisors
Prof Matt Berriman, School of Infection and Immunity, University of Glasgow, School of Infection and Immunity
Dr William Haese-Hill , MVLS Shared Research Facilities, University of Glasgow
Prof Aaron Maule, School of Biological Sciences, Queen’s University Belfast
Summary
The liver fluke (Fasciola hepatica) is a major livestock parasite, costing UK agriculture tens of millions annually and increasingly resistant to available drugs. Across the animal kingdom, multiple protein variants are made from single genes through alternative splicing — but in parasitic worms this process is poorly charted and greatly impeded by incomplete and inaccurate genome annotations.
This project will investigate how alternative splicing changes as liver flukes develop through their complex life cycle. You will determine whether these changes reflect genuine regulation or shifting tissue composition, and investigate their functional consequences. You will extend and apply a computational workflow, built around visualisation within a genome browser, to existing transcriptomic datasets, use long-read sequencing to establish the true structure of candidate transcripts, and use RNA interference in living parasites to first disrupt splice regulation globally, before investigating selected genes in greater detail by comparing the effects of silencing individual transcript isoforms and the gene more broadly.
You will gain critical interdisciplinary skills for bioscience. Computational training will include programming (in Python, R and JavaScript), analysis of short-, long-read and single-cell RNA-seq data, and professional software development practice (including version control, testing and workflow management). Laboratory training will cover parasite cultivation, molecular biology, long-read sequencing library preparation, RNA interference and parasite phenotyping.