The 2007 GE Healthcare Life Sciences Award: Graham Baldwin

Department of Surgery, University of Melbourne

Graham BaldwinGraham Baldwin is an Associate Professor and NHMRC Senior Research Fellow in the University of Melbourne Department of Surgery at the Austin Hospital. His biochemical career began at the same university, where he completed a PhD degree with Barrie Davidson in the Russell Grimwade School of Biochemistry in 1975. His interest in the biology of metal ions was aroused during a postdoctoral fellowship in the Oxford laboratories of Professor Edward Abraham, where he worked on a Zn2+-dependent β-lactamase II responsible for the inactivation of penicillins and cephalosporins. He continued to study metalloenzymes (in this case the Mn2+-containing pyruvate carboxylase) with Bruce Keech and John Wallace in Adelaide during his tenure of a Queen Elizabeth II Fellowship.

In 1981, Tony Burgess was establishing the Melbourne branch of the Ludwig Institute for Cancer Research. Graham was recruited to join in an investigation of the role that growth factors play in the development of gastrointestinal cancer. For the intervening 25 years, much of Graham's work has concentrated on the peptide hormone gastrin, which has been recognised for over a century as a major stimulant of acid secretion by the stomach. The gastrin field has undergone a recent renaissance with the demonstration that gastrin precursors act as growth factors in the gastrointestinal tract, where they stimulate cell proliferation and migration, and accelerate the development of colorectal cancer. Since 1994, Graham has been based at the Austin Hospital in Heidelberg, where he works with Arthur Shulkes, Chris Christophi and a talented team of colleagues on the biological activities of gastrins and other regulatory peptides.

A highlight of Graham's recent work has been the discovery that gastrins bind two ferric ions with high affinity. Binding was demonstrated by classical biochemical techniques such as absorbance, fluorescence and, together with Ray Norton, NMR spectroscopy. Unexpectedly, ferric ions are essential for the biological activities of gastrin precursors, but dispensable for the activities of mature gastrin. This work is the first demonstration of an essential role for metal ions in the action of any hormone, and presages the possibility of new treatments for colorectal carcinoma and other proliferative disorders of the gastrointestinal tract. In collaboration with Greg Anderson at Queensland Institute of Medical Research, the demonstration that circulating gastrin concentrations are increased in mice and humans with the iron overload disease haemochromatosis further suggests that gastrin and iron homeostasis might be interrelated.

Biochemistry is full of cycles, so it's appropriate that metal ions have again become one of Graham's central research interests. Perhaps the most satisfying aspect of a long career in biochemistry is the fact that the technical advances of the last 30 years now allow us to answer the questions that before we could only ask. The challenge for the next decade will be to turn those answers into practical treatments for human disease.