Membrane protein structure and interactions
Membrane proteins represent the next significant challenge in structural biology. While it is estimated that a third of the human genome encodes for membrane proteins, the structures of only relatively few membrane proteins are currently known. It will be some time before membrane protein structure determination becomes routine, yet over 50% of the drugs on the market today rely on the activity of membrane proteins for their efficacy. This project seeks to develop and apply novel techniques and approaches to study the structure and interactions of membrane proteins. A range of techniques for studying membrane interactions, including biosensor, fluorescence and NMR technologies, are being used for the study of membrane proteins.

Biologically active peptides: the relationship between structure and activity
We have identified peptides from the skin glands of frogs and toads which are amongst the most powerful biologically active compounds in the animal kingdom. The aims of this project are to investigate the relationship between the structure and biologically activity of chosen groups of peptides including pheromones, anticancer and antibiotic peptides, and peptides which inhibit neuronal nitric oxide synthase. Possible applications would be of major benefit to society, e.g. if the sex pheromone of the cane toad could be used to reduce its population, or if an anti-cancer active peptide of clinical applicability could be produced. Solid-state NMR is being used to determine the insertion and structure of these peptides in model membranes, since these peptides act by lysing bacterial or animal membranes.

Membrane interactions and neurotoxicity of Amyloid Abeta peptides from Alzheimer's disease
A consequence of the increase in human life span is that age-related neurodegenerative diseases such as Alzheimer's disease (AD) are more prevalent. Currently there are limited therapeutic treatments and no cure for AD. AD is characterized by the abnormal accumulation of amyloid beta peptide (Abeta) into insoluble aggregates called plaques but there is increasing evidence indicating that the soluble form of Abeta is the toxic species. Abeta-induced toxicity may be mediated by binding to cell membranes via the lipid phosphatidylserine (PS). We seek to establish if there is a link between Abeta neurotoxicity, membrane binding, lipid peroxidation and affinity to PS; and if metal ions modulate the membrane interaction. Mutant Abeta peptides will be synthesized to determine which amino acids are involved in membrane binding. Co-localization of Abeta with PS in model and cell membranes is being studied by solid-state NMR and fluorescence techniques. By establishing which lipid is critically involved in membrane binding of Abeta and mediating subsequent cell death, drugs may be developed to prevent the binding of Abeta to membranes resulting in neuronal survival and prevention of memory loss in AD patients.

Membrane structure and lipid interactions of the pore-forming toxin Equinatoxin II by NMR.
The structure of Equinatoxin II, a pore-forming protein, is being studied in model cell membranes using solid-state NMR spectroscopy. The relationship of molecular structure to bioactivity and the nature of the pore-forming mechanism of this toxin will be determined. The results will aid in understanding how toxins lyse cells and could lead to the design of improved antibiotic peptides. Currently the structure of membrane proteins are difficult to determine and the newly developed techniques used for the structural determination of this membrane-associated protein will be suitable for studying other membrane proteins and receptors of pharmaceutical importance.

Development, evaluation and applications of novel ionic liquids
This project is a collaboration between the major Australian chemical company, Orica, CSIRO - CMIT, and Monash University. The aim is to develop highly novel processes using ionic liquids as catalysts and/or facilitating agents to: promote miscibility of materials, generate new redox/electrochemical reactions to dissolve materials, optimise the temperature initiation of the catalytic activity, and control a condensation reaction leading to improved products like adhesives, resins and nano-particle condensates. The project is based on design, synthesis and application developments with ionic liquids tailored to the production conditions of Orica's chemical products. The outcome of this work will help to develop better catalysts and processes with the ability to reduce the cost in terms of energy and carbon dioxide emission.