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Controlling wombat mange by targeting scabies ligand-gated chloride channels


Project Description

The scabies mite (Sarcoptes scabiei) is an ectoparasite of global significance. In Australia, the common wombat (Vombatus ursinus) is highly susceptible to sarcoptic mange, where the disease is often fatal resulting in substantial population declines. Achieving sustainable control for sarcoptic mange is problematic. Current options usually involve macrocyclic lactones (e.g. ivermectin, moxidectin, milbemycin). However, no current treatments are ovicidal, nor do they persist in effective concentrations over the mite life cycle. Thus, population-level control of mange is challenging, and current approaches are likely to promote the development of drug resistance. Since the most effective existing acaricides act on inhibitory receptors for GABA and glutamate receptors, characterising this receptor family is of critical importance, especially in the context of emerging drug resistance. This project will use bioinformatics, RNA sequencing, RT-PCR, and high-throughput functional expression assays to comprehensively annotate and functionally characterise the ligand-gated chloride channel (LGIC) superfamily in scabies mites. We will also conduct surveys of mites from wombat populations across Australia treated with different acaricides to assess the frequency and functional consequences of receptor variants that may contribute to potential drug resistance. Lastly, the project will characterise several unique mite receptors that could represent novel targets for the next generation of acaricides.

HDR students working on this project will have the unique opportunity to receive training in bioinformatics analysis, molecular biology (PCR, cloning, mutagenesis) and structure-function assays encompassing biochemistry, cell culture, in vitro toxicity assays, microscopy and high-throughput screening methods. The project will be based in a new state-of-the-art molecular biology laboratory at the Sunshine Coast Health Institute (https://www.usc.edu.au/learn/why-choose-usc/study-locations/research-and-teaching-centres/sunshine-coast-health-institute) under the supervision of Professor Robert J Harvey, who has expertise in the molecular genetics of vertebrate and invertebrate ligand gated ion channels in health and disease - https://orcid.org/0000-0001-5956-6664 and Dr Kate Mounsey, an international expert in clinical, molecular and immunological features of Sarcoptes scabiei - https://orcid.org/0000-0003-0579-9424.

To apply, please follow the instructions at: https://www.usc.edu.au/learn/what-will-i-pay/scholarships/research-scholarships/scabies-molecular-genetics-phd-scholarship

Funding Notes

The scholarship is open to domestic applicants only. Candidates must not have an equivalent qualification to the one for which they are currently applying. Candidates must have a First-Class Bachelor Honours Degree, or show equivalent level of achievement with other academic qualifications or professional research experience. Ideal candidates will have had previous experience in the areas of molecular biology, biochemistry, or genetics. Applications will be accepted until 15th February 2020. Note that incomplete applications will not be considered.

References

References:
1. Fraser TA, Carver S, Martin AM, Mounsey K, Polkinghorne A, Jelocnik M (2018) A Sarcoptes scabiei specific isothermal amplification assay for detection of this important ectoparasite of wombats and other animals. Peer J 6:e5291.
2. Mounsey KE, Walton SF, Innes A, Cash-Deans S, McCarthy JS (2017) In vitro efficacy of moxidectin versus ivermectin against Sarcoptes scabiei. Antimicrob Agents Chemother. 61 pii:e00381-17.
3. Mounsey KE, Dent JA, Holt DC, McCarthy J, Currie BJ, Walton SF (2007) Molecular characterisation of a pH-gated chloride channel from Sarcoptes scabiei. Invert Neurosci. 7:149-156.

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