Project Reference: TRG27-ZOO-IH1

Project title: Exploring newly characterised invertebrate neurotransmitter receptors with potential for anti-parasitic drug development

Project outline

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.

One of the most successful classes of anthelmintics targets ligand-gated ion channels (LGICs), which control fast synaptic transmission in the nervous system. Unlike vertebrates, nematodes possess a remarkably diverse repertoire of LGICs, many of which are found only in nematodes and other invertebrates. This has enabled the development of highly selective drugs, such as ivermectin.

We have recently identified several previously uncharacterised LGIC families in the free-living nematode C. elegans. Many of these receptors are unique to nematodes and display unusual pharmacological properties, making them promising targets for the development of new, more selective anthelmintics. The aim of this project is to identify and characterise these receptors in parasitic nematodes using a combination of phylogenetics, electrophysiology, structural biology and behavioural analysis.

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.

Principal Supervisor

Dr Iris Hardege

Email address: ih287@cam.ac.uk

Department / Partner Institute: Zoology

Website: https://www.zoo.cam.ac.uk/groups/hardege-group-0

BBSRC strategic theme

Bioscience for sustainable agriculture and food