THE 2005 LEMBERG MEDAL: IAN YOUNG
Ian Young is Professor of Molecular Biology and head of the Cytokine Molecular Biology and Signalling Group in the John Curtin School of Medical Research, Australian National University. Originally from Melbourne, he completed an MSc degree at Melbourne University in 1964 and a PhD degree under the supervision of Frank Gibson at the Australian National University in 1969. He continued at the John Curtin School of Medical Research and was appointed Head of the Medical Molecular Biology Unit in 1984, Head of the Division of Biochemistry and Molecular Biology from 1989-2003 and interim Director in 1992 and 1998. Despite serving in senior administrative positions, his major interest has always been research. He was LKB Medallist of the ASBMB in 1985.
Ian’s research has been in two main areas. The first is the biosynthesis and function of the aromatic vitamins derived from chorismic acid, the major branch point compound of aromatic biosynthesis. This work began in Frank Gibson’s lab and subsequently continued independently. The major details of the biosynthetic pathways to ubiquinone, menaquinone and the iron- binding compound, enterochelin, were elucidated. The role of ubiquinone and menaquinone in electron transport, the role of enterochelin in iron transport and the sequence and enzymology of respiratory dehydrogenases were also studied. In 1979/80 he spent a year’s study leave with Fred Sanger at the Laboratory of Molecular Biology in Cambridge participating in the sequencing of the human and bovine mitochondrial genomes. He cloned the bovine mitochondrial genome and coordinated its sequencing. The DNA sequences revealed much new information, including an altered genetic code and novel transfer RNAs.
His work on cytokine molecular biology began in the early 1980s. The mouse interleukin-3 (IL-3) gene was cloned in 1984 with Andrew Hapel. This was the first cloning of a colony stimulating factor and enabled research on abnormal expression of IL-3 and leukemia. The human IL-5 gene was cloned with Colin Sanderson in 1987 paving the way for important biological studies. He collaborated with Klaus Matthaei and Manfred Kopf to generate an IL-5 deficient mouse in 1996. Evidence of a key role for IL-5 and eosinophils in allergic inflammation was obtained with Paul Foster using a mouse model of asthma. The IL-5 deficient mouse provided the stimulus for much important work on the role of cytokines and chemokines in allergic inflammation and of eosinophils in parasite infections.
The cytokines IL-3, IL-5 and GM-CSF signal through a common receptor and his recent research has been on the structural biology of this system. The main signalling entity, the β common receptor, was crystallised and its X- ray structure determined in 2001 with David Ollis. The receptor is an interlocking dimer in the absence of ligand and thus unlike any other class I cytokine receptor described thus far. Supporting evidence, including work on mutagenesis of the receptor, was obtained for the involvement of the β dimers in signalling. The structural studies coupled with new work on growth and differentiation offer the promise of new insights into the role of the β common receptor system in inflammation and leukemia.