Lecturer CONTACT DETAILS:
Address: Bio21 Institute, School of
Chemistry, University of Melbourne, Parkville, VIC 3010 Australia
Room: Bio 21 Inst. 532
Email: sjwill@unimelb.edu.au Teaching responsibilities Field of expertise
Biological Chemistry and Carbohydrates In our laboratory we are interested in the application of organic chemistry to the study of biological systems. Our work requires the synthesis of carefully designed molecules and their application in a variety of biological systems.
Sulfatases: Mechanism of catalysis and inhibition
Sulfate esters are remarkably widespread in nature where their presence mediates a variety of biological processes. Sulfatases are enzymes that cleave sulfate esters from organic molecules and are involved in environmental nutrient cycling, in the progression of hormone dependent breast cancers, and in the remodelling of sulfated glycosaminoglycans in the developing embryo. In this project we are studying the mechanism of these enzymes in detail through the synthesis of substrates, competitive inhibitors, and time-dependent inactivators. We then use these compounds to study enzyme mechanism using sulfatases that we express in-house.
Mannose metabolism in pathogenic organisms
Carbohydrate processing is one of the basic core metabolic pathways of all organisms. We are investigating aspects of mannose metabolism in two pathogenic microorganisms, Mycobacterium tuberculosis, the causative agent of tuberculosis, and leishmania, an insect borne agent responsible for leishmaniasis. Our research involves the synthesis of new substrates and inhibitors of various mannose-processing enzymes involved in the biosynthesis of essential cellular molecules. This program of research is performed in collaboration with the laboratories of A/Prof. Malcolm McConville and Dr. Helen Billman-Jacobe.
Medicinal chemistry: Flavonols as preventative agents for coronary heart disease. As part of a collaboration with the research group of A/Prof. Owen Woodman in the Department of Pharmacology we have been synthesizing new flavonoids to optimize the beneficial actions of these naturally occurring compounds as treatments for coronary heart disease and stroke. Flavonoids are polyphenolic compounds found in foodstuffs including fruits and vegetables. In populations with a high dietary intake of fruits and vegetables there is a lower incidence of coronary heart disease, which has been linked to the beneficial action of flavonoids. Compounds are tested for antioxidant effect and for their influence on vascular tone in a rat model of coronary heart disease.
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naturally occuring sulfate esters
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Mannose-containing glycolipid from mycobacteria
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New single-action antioxidant flavonols
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For further information visit the Williams group research page
Selected
Publications:
- Williams, S.J.; Notenboom, V.; Wicki, J.; Rose, D.R., and Withers, S.G., J. Am. Chem. Soc., 2000, 122, 4229-4230.
- Williams, S.J., and Davies, G.J., Trends in Biotechnology, 2001, 19, 356-362.
- Williams, S.J.; Senaratne, R.H.; Mougous, J.D.; Riley, L., and Bertozzi, C.R., J. Biol. Chem., 2002, 277, 32606-32615.
- Gloster, T.; Williams, S.J.; Tarling, C.; Roberts, S.; Dupont, C.; Jodoin, P.; Shareck, F.; Withers, S.G., and Davies, G.J., Chem. Commun., 2003, 944-945
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