Projects that were available for PhD and Honours Students


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NEUROPHARMACOLOGY

The Good Stuff in Herbs

The physiological basis of action of many herbal remedies is still relatively unknown, even though these compounds are commonly consumed. GABA-A receptors play an important role in most brain functions, and have been shown to be important targets of plant extracts, such as resveratrol from red wine, flavanones from chamomile tea, and thujone from absinthe, as well as herbs such as kava kava, gingko, valerian and passion flower. Projects will involve investigating the effects of extracts and active constituents from commonly consumed herbal remedies mentioned above on GABA-A receptor function.

Projects will involve the isolation and characterization of active constituents of herbal remedies using techniques such as:

  • chromatography
  • spectroscopy (NMR, mass spectroscopy)
  • X-ray crystallography

How does ginkgo work?

Bilobalide, and ginkgolides A, B, and C are the active constituents of the 50:1 ginkgo Ginkgo biloba leaf extract used worldwide for the symptomatic treatment of cerebral and peripheral insufficiency and dementia. These compounds may be involved in the cognition enhancing effect of the ginkgo extract. We have shown that they were noncompetitive blockers of GABA receptors with a similar mechanism of action to that of the chloride channel blocker picrotoxinin. GABA-A and GABA-C receptors are members of a super-family of ligand-gated ion channel receptors that also include the nicotinic acetylcholine (nACh) and serotonin 5-HT3 receptors. The amino acids in the subunit transmembrane proteins that make up the channel of these receptors are highly conserved in this super-family. Picrotoxinin blocks the channel of all members in this superfamily with wide variation in potencies. It is most potent at GABA receptors and only weakly to moderately potent at glycine, nACh and 5-HT3 receptors. Bilobalide, ginkgolide A, B and C are structurally similar to picrotoxinin. Honours project will involve evaluating the effects of bilobalide, ginkgolide A, B and C on wild type nACh receptors expressed in Xenopus oocytes using 2-electrode voltage clamp methodology.

Projects will involve the biological and pharmacological evaluation of the active constituents of herbal remedies, using techniques such as:

  • general observation and toxicity tests (Irwin tests)
  • behavioural tests for anxiety, sedation and memory
  • quantitative receptor autoradiography for binding to GABA-A receptor sites in animal brain

Projects will involve pharmacological evaluation of the active constituents of herbal remedies using techniques such as:

  • testing constituents on GABA-A receptors expressed in Xenopus oocytes
  • radioligand binding for binding to GABA-A receptor sites in animal brain

Aspects of these projects may be carried out in collaboration with Mary Collins and Jane Hanrahan in the Faculty of Pharmacy.

Techniques used in the laboratory

Our group uses a multidisciplined approach to research and many different techniques may be learned. We use:

  • Molecular biology;
  • Electrophysiology;
  • Cell culture;
  • Radio-ligand binding;
  • In situ hybridisation;
  • Immunohistochemistry;
  • Autoradiography;
  • Molecular modelling; and
  • Chemistry


NEUROCHEMISTRY/NEUROPHARMACOLOGY

GABA and schizophrenia

The possible roles of GABA in schizophrenia are being examined in collaboration with the Schizophrenia Research Institute using facilities provided by the NISAD Centre for Collaborative Human Brain Research at the University of Sydney. Prospective honours students are encouraged to discuss possible projects with the above named researchers.