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2007 ASBMB Award: Sarah Linke
School of Molecular and Biomedical Science, University of Adelaide
Sarah completed a BSc (Molecular Biology) at the University of Adelaide majoring in biochemistry and pharmacology, including two biochemistry research projects. Under the supervision of Murray Whitelaw and Daniel Peet, her Honours project entailed characterising the substrate recognition requirements of the newly discovered asparaginyl hydroxylase, FIH-1. FIH-1 acts as a cellular oxygen sensor to regulate the transcriptional activity of the hypoxia-inducible transcription factor-α (HIF-α). This work, involving kinetic comparison of single-alanine mutant substrates in vitro coupled with cell-based reporter gene assays, was awarded a poster prize at ComBio2004 in Perth, and was published in Journal of Biological Chemistry that same year. Sarah's continued interest in characterising FIH-1 inspired her to commence her PhD investigating novel FIH-1 substrates, supervised by Daniel Peet in his newly established hypoxia laboratory at University of Adelaide. She utilised bacterial and mammalian cell-based expression techniques, affinity chromatography and an in vitro hydroxylation method to purify a suspected FIH-1 substrate, the Notch receptor. Mass spectrometry of Notch, performed by Queensland collaborators Jeffrey Gorman and Tristan Wallis (at Queensland Institute of Medical Research), demonstrated an FIH-1-dependent hydroxylation. Sarah presented these novel findings at the 2006 Keystone hypoxia meeting in Colorado and visited collaborators Lorenz Poellinger and Urban Lendahl of the Karolinska Institute (Sweden) to plan methods for identifying the function of the hydroxylation. Sarah's continued work on this project has since defined a second hydroxylation site in Notch, and she has examined both sites with in vitro hydroxylation and binding assays. These data are currently being collated for publication, together with functional effects defined by her Swedish collaborators.
The ASBMB Fellowship will allow Sarah to visit Sweden to discuss methods with collaborators, and to attend the 2008 Keystone hypoxia meeting in Vancouver to present a completed picture of the hydroxylation of the Notch receptor.
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This page last modified: October 10, 2008.