How do pheromones influence parasite infectivity?
Dr J Dalzell
Dr S Cochrane
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
Parasitic nematodes cause disease and morbidity in livestock and humans, and many species are parasites of crop plants, seriously threatening global food security. Understanding how parasitic nematodes regulate behavior at a molecular level is crucial for the identification of novel drug targets. This is especially important as drug resistance is rising. It has been shown that population-level behaviors can be influenced by nematode-specific pheromones known as ascarocides. Our preliminary data implicate ascarocide signaling in the modulation of parasite infectivity, however the molecular mechanism by which this occurs is unknown. This interdisciplinary project will involve the chemical synthesis of a library of ascarocides, including novel “photo-tagged” analogues, which will be used to identify the ascaroside receptor(s) through photo-affinity labelling. Furthermore, the library of ascarosides will enable behavioral and molecular analysis of nematode responses, using transcriptomics and functional genomics approaches, to identify the molecular basis of behavior. Identification of the ascarocide receptor(s) will allow binding sites to be determined by MS/MS analysis of ascaroside-receptor conjugates. This could facilitate the rational design of novel anti-parisitic compounds. The successful applicant will gain interdisciplinary training in organic synthesis, biochemistry, bioinformatics, molecular and behavioural biology.
Research aims (max. 75 words)
1) Synthesise a modular library of natural and unnatural nematode ascarocide pheromones
2) Identify the ascaroside receptor(s) by photoaffinity labelling
3) Define the behavioural and transcriptomic response of various parasitic nematodes to ascarocide exposure
4) Functionally validate ascarocide-regulated genes using RNA interference
5) Identify the ascaroside binding site on its protein-receptor
How good is research at Queen’s University Belfast in Agriculture, Veterinary and Food Science?
FTE Category A staff submitted: 33.40
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