Joel Mackay


School of Life and Environmental Sciences
University of Sydney

MackayI have spent the major portion of my career working to understand aspects of how genes are switched on and switched off.

After BSc and MSc degrees at the University of Auckland, I ventured to Cambridge for a PhD with Dudley Williams in the Department of Chemistry. It was here that my interest in molecular recognition was born, with Dudley asking fundamental questions about the physical chemistry underlying biomolecular interactions and using this information to draw conclusions and make predictions about systems such as antibiotic activity. It was also here that I became attached to NMR spectroscopy as a tool for probing protein structure and function.

Two years as an ARC Postdoctoral Fellow in Glenn King’s lab at the University of Sydney (1995–6) reinforced the lessons I’d learned with Dudley about trying to ask important questions and doing rigorous science – and also brought the realisation that not all groups play cricket *in* the lab.

Since 1997, I have stayed put and built a lab with the assistance of fellowships and grants from the ARC and NHMRC. It has all been built fundamentally on a collaboration with Merlin Crossley, through an initial approach he made to Glenn – to probe the structural basis for an interaction between two zinc-finger domains.

Early research highlights were (i) the realisation that zinc-finger domains can act as protein recognition modules – an idea that still has a huge amount of potential to direct our understanding of transcriptional regulation and (ii) elucidation of the molecular mechanism of action of the protein chaperone of alpha hemoglobin (work driven by David Gell while he was at the University of Sydney). These projects have led to efforts to develop new research tools, such as our DNA/RNA Pentaprobes, and attempts to engineer new classes of RNA-binding proteins. The latter was less successful than we had hoped for, but the former has proven very popular.

More recently, we have been getting excited about the structural and mechanistic details of chromatin remodelling, as executed by the nucleosome remodelling and deacetylase complex – a project that I suspect will occupy us for the next 20 years. We are also trying to understand the importance of post-translational modifications in transcription factors – in what would be an expanded histone code.

Finally, I have also enjoyed involvement for the last eight years in the CSIRO Scientists in Schools program. Through this and a range of other school activities, I’ve tried to get the next generation excited – not necessarily about doing science themselves even, but in understanding how important it is to ask sensible questions.