Professor Ross Smith

Professor

School of Chemistry and Molecular Biosciences
Faculty of Science
ross.s@uq.edu.au
+61 7 336 54627

Overview

RNA trafficking in cells.

Our major interest is in the post-transcriptional control of gene expression. Our principal focus is currently on the molecular and cell biology of the heterogeneous nuclear ribonucleoprotein (hnRNP) A/B family of protein molecules. These fascinating multi-tasking proteins function in both the cytoplasm and nucleus. In the former location they are involved in control of trafficking and translation of mRNAs. In the nucleus they participate in such diverse processes as RNA packaging, telomere maintenance, alternative mRNA splicing, and RNA export. In all of these roles they recognise small cis-acting elements in the RNA or DNA molecules (Hoek et al., 1998; Munro et al., 1999).

For more information, see Research Interests…

Research Interests

  • RNA trafficking in cells.
    Alternative splicing of mRNA generates multiple proteins from a single gene: the famous Drosophila Dscam gene is thought to generate over 38,000 protein isoforms (more than twice the total number of Drosophila genes). The hnRNPs get into the act in two ways. First, they modulate alternative splicing of multiple mRNAs by antagonising the actions of SR proteins, thus affecting post-transcriptional expression of many genes. Secondly, the hnRNP mRNAs are themselves alternatively spliced. Alternative splicing and over-expression of hnRNP A2/B1 appears to promote cell proliferation in several cancers. A second hnRNP A/B nuclear function is in the maintenance of the telomeres that cap the ends of eukaryotic chromosomes. hnRNP A2/B1 binds the TTAGGG telomere repeat sequence and appears to influence telomere length. It is thus involved in cell proliferation, cell senescence and cancer and apoptosis. We are also interested in the role of hnRNPs in cytoplasmic trafficking of mRNA. hnRNP A2 mediates association of mRNAs possessing an 11-nucleotide A2RE cis-acting element with transport granules in oligodendrocytes (Munro et al., 1999) and neurons (Shan et al., 2003). Its role in neurons is of special interest. In these cells a subset of mRNAs is expressed and localised in response to synaptic activity in a pattern that implicates the proteins they encode in long-term potentiation and memory formation. Much of this work has been part of a collaboration with Professors John Carson and Elisa Barbarese of the University of Connecticut Health Center at Farmington. We also have collaborations other groups including the labs of Joe Rothnagel (UQ), Melissa Brown (UQ), Ian Brereton (UQ), Luke Guddat (UQ), Roger Reddel (Children's Medical Research Institute, Sydney) and Jenny Beck (University of Wollongong). Another major interest is in protein structure and function. We were the first group world-wide to determine the three-dimensional structure of modules of the low-density lipoprotein receptor (LDLR), which plays a central part in cholesterol metabolism (the initial paper was submitted on our behalf to PNAS by Nobel prizewinner Prof. Michael Brown). We have subsequently determined the structures of many LDLR modules and concatenated modules (Daly et al., 1995a; Daly et al., 1995b; Atkins et al., 1998; Kurniawan et al., 2001; Clayton et al., 2000; Kurniawan et al., 2000). More recently our focus has been on the structures of single-stranded RNA- and DNA-protein complexes, with the aim of understanding how single-stranded base sequences are "read" by proteins. Such recognition is essential for each of the roles of the hnRNPs. The structures are being determined by X-ray crystallography and nuclear magnetic resonance spectroscopy. Our lab is in a modern building on the St. Lucia campus of the University of Queensland, which by most criteria is in the top 1-3 of Australian universities. We have access on campus to a wide array of state-of-the-art instrumentation and facilities, including 750 MHz NMR spectrometer, MALDI-TOF and ES-qQ-TOF mass spectrometers, real-time PCR equipment, confocal and deconvolution fluorescence microscopes, Edman protein sequencer, cryo-X-ray diffractometers, dynamic light scattering equipment circular dichroism, and photon-counting fluorescence spectrometers, cell microinjectors, and bacterial and insect protein expression facilities.

Qualifications

  • B.Sc (Hons), University of Canterbury
  • PhD, University of Canterbury

Publications

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Publications

Journal Article

Conference Publication

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

  • Master Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Associate Advisor

  • Master Philosophy — Associate Advisor

Completed Supervision