Evolution and pharmacology of novel neurotransmitter receptors in parasitic nematodes

Field

Supervisor: Iris Hardege

Project Summary (PhD): 

Parasitic nematodes are a major burden for agriculture, veterinary and human health. Plant parasitic nematodes are estimated to cause over $150 billion in crop losses each year, while parasitic worms infect more than 1.5 billion people worldwide. Control of these parasites relies on a small number of anthelmintic drugs and pesticides, but resistance is becoming increasingly widespread, creating an urgent need for new parasite-specific drug targets.
 

Type of Work:

The student will combine computational and experimental approaches to identify and characterise novel LGICs from parasitic nematodes, this is likely to include:

  1. Phylogenetics. Identify and classify LGIC families across parasitic nematodes using comparative genomic and phylogenetic analyses.
  2. Pharmacology. Express candidate receptors in Xenopus oocytes and use two-electrode voltage clamp electrophysiology to determine their functional and pharmacological properties.  
  3. Behaviour. Investigate the physiological role of these receptors using behavioural assays in nematodes and assess their potential as targets for novel anthelmintic compounds.                                                                                                                                  

There is also scope for the student to build on this project and work with collaborators to explore novel mechanisms for targeting receptors such as nanobodies.

Importance of the area of research concerned:

This project will improve our understanding of how nervous systems have evolved across the nematode phylum and uncover the function of previously unstudied receptor families. By identifying ion channels that are unique to parasitic nematodes, this work could reveal new targets for the development of selective anthelmintic drugs, helping to address the growing problem of drug resistance in parasites affecting crops, livestock and humans.

References:

Iris Hardege, J Morud, A Courtney, WR Schafer. A Novel and Functionally Diverse Class of Acetylcholine-gated Ion Channels. Journal of Neuroscience (2023) https://doi.org/10.1523/JNEUROSCI.1516-22.2022    Iris Hardege, J Morud, J Yu, TS Wilson, FC Schroeder, WR Schafer. Neuronally Produced Betaine Acts via a Ligand Gated Ion Channel to Control Behavioural States. PNAS (2022) https://doi.org/10.1073/pnas.2201783119   TM McRunnel, TE Reynoldson, Y Zhu, T Rahman, Iris Hardege. Mechanistic dissection of a dopamine-gated cation channel from Daphnia reveals key determinants of ligand selectivity and sensitivity. bioRxiv (2025) https://doi.org/10.1101/2025.10.31.685654