2005 ASBMB Fellowship: Geoffrey Kong

Geoffrey Kong Since secondary school, I have wondered how my interests in maths and biology would reconcile. I finally saw the light towards the end of my BSc course at the University of Melbourne, when I had my first exposure to X-ray crystallography in lectures given by one of my current supervisors, Professor Michael Parker. I joined his laboratory at St Vincent's Institute for my Honours year in 2001 and stayed on since. With the change of project for my PhD I became jointly supervised with Dr Roberto Cappai from the Department of Pathology, University of Melbourne.

My Honours project involved the crystallographic studies of several folding mutants of human pi-class glutathione transferase (GST) to understand the structural importance of a couple of motifs conserved in the GST family. The five structures determined in that year gave me good grounding for my PhD project, on the study of copper ion binding to the Alzheimer's disease amyloid precursor protein (APP). Various experiments suggested that the binding interaction reduced the cleavage of APP into the A peptide, which is thought to trigger the cascade of events leading to Alzheimer's. By studying the structural details of the interaction, we hope to understand the underlying mechanism that explains the effect of copper, and use the structural information to find non-toxic substitutes that mimic the beneficial effects of copper. I have obtained the structure of the copper binding domain of the APP bound with copper, and identified two histidines, one tyrosine and two water molecules as ligands arranged in a distorted square pyramidal geometry. I am in the process of verifying the coordination geometry by techniques such as X-ray absorption spectroscopy and finishing a preliminary search for copper mimetics that bind to the copper binding domain.

I have come to appreciate the versatility of X-ray techniques, and maths has certainly helped! Crystallography is equally a broad field, and one of the best ways to learn about it is through a conference meeting researchers with similar interests. I am very grateful to the ASBMB for supporting my attendance at the International Union of Crystallography Congress in Italy this August through the Travelling Fellowship.

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This page last modified: October 10, 2008.