2004 Applied Biosystems Edman Award: David Gell

David Gell Following undergraduate studies in the UK, I was fortunate to take a research job with Steve Jackson at the Wellcome Trust/Cancer Research UK Gurdon Institute at the University of Cambridge. Becoming hooked on research, I stayed in Steve's lab for my PhD studies on essential DNA repair factors in mammalian cells. It was a very exciting time to be working on DNA repair, and particularly on DNA double-strand break repair in eukaryotes, which was then the primary focus of Steve's lab. This period, through the mid- to late-nineties, saw the discovery of many key players in DNA double-strand break repair, and I was involved in the cloning and characterisation of one of these - the large catalytic subunit of DNA-dependent protein kinase (DNA-PK). This enzyme was the first protein kinase found to recognise, and become activated by, DNA double-strand breaks. Indeed, mutations in any of the three DNA-PK subunits turned out to cause severe DNA-repair defects. Through studying protein-protein interactions between the DNA-PK subunits, which regulated activity of the enzyme, I developed a general interest in the role of biomolecular interactions in the regulation of biological processes.

Supported by a Wellcome Trust Travelling Fellowship, the opportunity to join Joel Mackay's lab at the University of Sydney came at a great time, and allowed me to think more about the structural aspects of protein interactions in transcriptional regulation. In Joel's lab I have been exposed to a wide range of biophysical methods, opening up a whole new world of appreciation for the molecular dynamics of cellular processes. A Mackay lab interest in the regulation of blood cell development led me to investigate the structure and function of a novel protein, a-haemoglobin stabilising protein (AHSP). In collaboration with Dr Mitchell Weiss (Children's Hospital of Philadelphia, USA), we have shown AHSP is involved in protecting developing red blood cells from the toxic effects of excess α-haemoglobin production. Notably, Î±-haemoglobin toxicity is a major feature of β-thalassaemia disease. This work has demonstrated to me that, even the areas of biology that we know most about, there can still be so much more to learn.

The Applied Biosystems Edman Award will enable me to travel to the USA to meet with a number of key collaborators on the AHSP project. This will assist our future work understanding the function of AHSP, in an area of biology directly relevant to human health.

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