Faculties : A-Z Directory : Library

Bruce Livett

Biomedical neurochemistry: Molecular mechanisms of neurotransmission and signal transduction in endocrine and neuronal cells
In response to stress, the adrenal gland secretes adrenaline and noradrenaline and a number of neuropeptides into the circulation. Our laboratory is using primary cultures of bovine adrenal chromaffin cells to gain an understanding of the signal transduction pathways involved in the control of endocrine and neuronal function during stress. Cellular mechanisms of nicotine addiction and tolerance There is currently much interest and concern about nicotine addiction. Nicotine is now acknowledged as a key component in addiction to cigarette smoking and to withdrawal symptoms upon quitting smoking, however, little is known about the cellular mechanisms underlying these processes. We are currently using adrenal chromaffin cells in culture to study molecular and cellular mechanisms involved in nicotinic tolerance and withdrawal following chronic exposure to nicotine. This project will involve setting up a fast perfusion system to examine the role of high concentrations of the neurotransmitter, acetylcholine, on the alpha7 subunit combination of the nicotinic receptor. Receptor binding studies with a new radioligand, H-methyllycaconitine which targets the alpha7 nicotinic receptor, will be undertaken in parallel with functional assays of catecholamine release.

A coneshell, Conus textile, in the Livett laboratory tank
Marine neurotoxins Project 1. Novel marine neurotoxins as modulators of nicotinic receptor function and neurotransmitter secretion The marine environment is a rich source of novel organic compounds and biologically active peptides. Studies are under way in collaboration with organic chemists, protein/peptide chemists and molecular modellers, to investigate natural products from marine sponges, soft corals and cone shells as sources of nicotinic receptor blockers. After identification of candidate molecules, derivatives will be synthesized and tested for greater potency and/or selectivity in their actions. These, and similar compounds under study, are of potential value in the design of new drugs to treat neuropathic pain, schizophrenia, epilepsy, Parkinson's disease and Alzheimer's disease. Project 2. Conotoxin gene isolation and characterisation (In collaboration with Ken Gayler) This project will use techniques of molecular biology to search for novel conotoxin gene sequences in the venom apparatus of Australian cone snails. These sequences will be used to predict corresponding peptide toxin sequences which can be chemically synthesised and tested for their effects upon ion channel function in a range of biological assays. Project 3. The use of conotoxins to alleviate neuropathic pain (In collaboration with Zeinab Khalil, National Ageing Research Institute, tel: +61 3 9389 7148, email: z.khalil@nari.unimelb.edu.au) Neuropathic pain refers to pain associated with damage to nerves and is associated with many conditions, including surgery, cancer, AIDS, diabetes and shingles. The common use of opiates to treat these painful conditions is not always appropriate. The recent discovery that pain can be controlled by the non-opiate, natural conotoxin compounds produced by cone shells has led to clinical trials of conotoxins for the treatment of neuropathic pain. We have isolated a number of new conotoxins. The effectiveness of these conotoxins in alleviating pain will be examined in an animal model of neuropathic pain established in Dr Khalil's laboratory.
For more information, visit Bruce Livett's 'Cone shells & conotoxins' website

Contact the University : Disclaimer & Copyright : Privacy : Accessibility