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2002 ASBMB Fellowship: David Lando
David Lando
completed his Bachelor of Science degree in 1990 in the School of
Biological Sciences at Flinders University. Shortly after
completing his degree, David began working as a scientific officer
for Bresatec in its radionucleotide and customer oligonucleotide
divisions. In 1997, after six years at Bresatec, David decided to
return to University to undertake an Honours degree. His Honours
project focussed on the regulation of hypoxia-inducible
transcription factors (HIF) and was carried out under the
supervision of Dr Murray Whitelaw in the Department of Biochemistry
(now Department of Molecular Biosciences) at the University of
Adelaide. In his Honours year David demonstrated that the DNA
binding activity of one of the HIF factors, HIF-2a was regulated by
the redox factor Ref-1. Ref-1 was shown to specifically reduce a
cysteine residue in the basic DNA binding region of HIF-2a
increasing its affinity for DNA. David received First Class Honours
and decided to commence a PhD in the following year in the same
laboratory continuing his work on the HIF proteins.
The activation of the HIF proteins by low oxygen stress is a multi-step process involving both increased protein stabilisation and transcriptional potency. Protein stabilisation is a result of inhibition of protein degradation while increased transcriptional potency is a result of recruitment of transcriptional coactivators. During his PhD David has demonstrated that the transcriptional potency of the HIF proteins is regulated by asparagine hydroxylation. At normal oxygen levels the transactivation domains of the HIF proteins are hydroxylated at a specific asparagine residue by FIH-1, a novel asparagine hydroxylase enzyme. Exposure to low oxygen stress reduces the rate of asparagine hydroxylation by FIH-1 resulting in coactivator protein binding and increased transcriptional potency. The results of David's research have been published in scientific journals such as Science, Genes and Development and Journal of Biological Chemistry.
Being awarded the ASBMB Fellowship will help David present his work at the Keystone Symposium on Protein Phosphorylation and Mechanisms of Cellular Regulation, which will be held in Taos, New Mexico.
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This page last modified: October 10, 2008.