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  Natural toxins and their synthetic analogues as tools to study ion channels and as potential drugs and pesticides


   School of Life Sciences

  Dr I R Mellor  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

The project will use a combination of electrophysiological techniques such as voltage-clamp and patch-clamp with molecular biology and protein expression to understand how natural toxins and their synthetic analogues act on ion channels in the nervous system. This project will study the modes and sites of action of the toxins and assess their suitability for development as novel therapeutic agents or pesticides. Sources of active compounds that we are presently exploring include centipede venom and ladybird defensive secretions, but we can consider other novel sources. The project could also be directed towards the study of existing ion channel drugs and pesticides in order to better understand their modes and sites of action or to investigate problems in their use such as insecticide resistance. These studies also reveal much about the structure and function of ion channels.

Biological Sciences (4) Medicine (26)

References

1. Richards, D.P.; Patel, R.N.; Duce, I.R.; Khambay, B.P.S.; Birkett, M.A.; Pickett, J.A.; Mellor, I.R. (-)-Adaline from the Adalia Genus of Ladybirds Is a Potent Antagonist of Insect and Specific Mammalian Nicotinic Acetylcholine Receptors. Molecules 2022, 27(20), 7074.
2. Ngum, N.M.; Aziz, M.Y.A.; Mohammed Latif, L.; Wall, R.J.; Duce, I.R.; Mellor, I.R. Non-canonical endogenous expression of voltage-gated sodium channel NaV1.7 subtype by the TE671 rhabdomyosarcoma cell line. J Physiol 2022, 600, 2499-2513.
3. Luck, V. L.; Richards, D. P.; Shaikh, A. Y.; Franzyk, H.; Mellor, I. R. The effects of structural alterations in the polyamine and amino acid moieties of philanthotoxins on nicotinic acetylcholine receptor inhibition in the locust, Schistocerca gregaria. Molecules 2021, 26, 7007.
4. Thompson, A. J.; Verdin, P. S.; Burton, M. J.; Davies, T. G. E.; Williamson, M. S.; Field, L. M.; Baines, R. A.; Mellor, I. R.; Duce, I. R., The effects of knock-down resistance mutations and alternative splicing on voltage-gated sodium channels in Musca domestica and Drosophila melanogaster. Insect Biochem Mol Biol 2020, 122, 103388.
5. Patel, R. N.; Richards, D. P.; Duce, I. R.; Birkett, M. A.; Sattelle, D. B.; Mellor, I. R., Actions on mammalian and insect nicotinic acetylcholine receptors of harmonine-containing alkaloid extracts from the harlequin ladybird Harmonia axyridis. Pestic Biochem Physiol 2020, 166, 104561.
6. Kachel, H. S.; Franzyk, H.; Mellor, I. R., Philanthotoxin analogues that selectively inhibit ganglionic nicotinic acetylcholine receptors with exceptional potency. J Med Chem 2019, 62 (13), 6214-6222.

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