Science for Health
29 January 2013
Guy Dodson, emeritus Professor of Chemistry in the University of York and former Head of Structural Biology at NIMR, died on December 24th aged 75. He was an outstanding X-ray crystallographer, world-renowned for his research on the three-dimensional structure of biologically important proteins, particularly insulin, and for his studies of the mechanism of action of numerous enzymes. He also established two first-class centres for the study of proteins: the York Structural Biology Laboratory and the Structural Biology Group at NIMR.
In the Oxford University laboratory of Dorothy Hodgkin between 1967 and 1976 Guy played the leading role in determining the structure of the first polypeptide hormone, insulin. Later, in a major crystallographic paper, he related the hormone’s chemical and biological properties to its atomic structure.
His work on insulin continued following his move to York in 1976 especially with the use of mutant and chemically modified versions of the hormone designed for analysis of the hormone’s structure, assembly, and action. He also collaborated closely with laboratories in pharmaceutical companies for the preparation of insulins that could be used to improve diabetes therapy.
The numerous enzymes of biological and pharmaceutical interest studied in York included bacterial amylases, ribonucleases, DNA gyrase and fungal lipases. Guy’s work on lipases exemplifies the mechanistic detail for which his studies were noted. He determined the mechanism of action which involves a catalytic triad of Aspartic acid, Histidine, and Serine, as seen in serine proteases, and found that the catalytic site was only exposed by movement of a lid-like structure that increased the non-polar surface around the site, providing a mechanism for the characteristic activation of lipases at oil-water interfaces.
In both Oxford and York Guy skillfully organized large research groups, and in 1993 he was invited by the Medical Research Council to establish X-ray crystallography at NIMR through a joint appointment between MRC and York University. He was enormously successful. In the process he also played a major role in, and took great pleasure in, propagating the multidisciplinary research of NIMR not least through collaborative research on proteases involved in infection by the malaria parasite; on proteins involved in the control of RNA metabolism in tuberculosis; and on the structure of prions.
Guy never really retired. Through collaboration, his long-term interest in the cellular receptor for insulin and research on the malaria enzymes continued and both yielded outstanding success in the last months of his life, the former through a land-mark publication this month in Nature and the latter through the first solution of the structure of the catalytic domain of the malarial protease, PfSUB1.
Guy’s parents emigrated to New Zealand in 1926 and Guy and his twin brother Maurice were born in Palmerston North in 1937. He had two older sisters who were closely involved in his upbringing. He went to Dilworth school, Auckland, from 1946-1954 where he was a member of the first rugby XV and the first XI cricket team, a successful, prize-winning student, especially prominent in debating. He was particularly stimulated by the senior school mathematics and sciences teacher, Donald Gray, who encouraged lateral thinking, logical reasoning and intelligent questioning to achieve an understanding of processes rather than simply internalizing information. At Auckland University College, Guy graduated BSc science, chemistry major, in 1958, MSc chemistry with a thesis in crystallography in 1959, and PhD in 1962 for research principally using X-ray analysis combined with analytical chemistry.
At that time he was greatly attracted by the X-ray crystallography research on larger biological molecules in Dorothy Hodgkin’s laboratory in Oxford University and he came to Oxford as a post-doctoral research assistant. He stayed on as a research fellow until Dorothy’s retirement in 1976. He found her laboratory to be a paradise and it profoundly influenced his career and his life. In it he received a thorough grounding in biological perspectives from such scientific leaders as J.D. Bernal and Don Steiner and in chemical structure and mechanism from Jack Dunitz and Bob Williams. He also met and married Eleanor, to begin a unique and life-long partnership. Together, through Guy’s enthusiasm and knowledge of protein structure and Eleanor’s mathematical skills they began to accumulate, initially through their research on insulin, exceptional scientific success that led to their elections to the Royal Society. An invaluable product of this partnership was the extensive nurturing and mentorship of young scientists from York, and elsewhere, that frequently involved hospitality at their home in York. Their natural warmth and inclusiveness was greatly appreciated by generations of students and postdoctoral scientists.
From his chemistry background, and honed by many influences at Oxford, Guy developed a deep-rooted belief in the particular value to biology of crystal structures to inform and challenge chemical mechanisms. The Oxford environment also reinforced his political commitment and through research collaborations and contacts established there, he remained closely linked with, and supportive of, scientists in India, China, and Cuba. Perhaps most importantly he acquired a style of scientific leadership and association with fellow scientists that, together with his great charm, was extremely attractive and was clearly reflected in the ease with which co-workers and co-discussants from multiple disciplines and many countries sought his company.
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