BSc (Hons), PhD
Position: 
Professor of Molecular Biology
Room: 
Room 425
Phone: 
+61 7 336 54627/54625
Biography: 

I undertook my PhD in Physical Chemistry at the University of Canterbury in New Zealand. This was followed by about three years studying biological membranes at Duke University in North Carolina and a year and a half in the Institute Jozef Stefan in Ljubljana, Slovenia. My mentor at Duke was Charles Tanford, a very well known protein scientist and author (“The Physical Chemistry of Macromolecules”, “Proteins: the workhorses of cells” etc) who deduced the structure of antibody molecules before switching his attention to biomembranes (“The hydrophobic effect”). I subsequently held lectureships at the University of Sydney and La Trobe University before moving to Brisbane in 1983. I have spent sabbatical leave at McGill (Montreal), Oxford and Connecticut universities and the Scripps Research Institute (La Jolla, California).

Research Focus and Collaborations: 

We are interested in RNA-binding proteins and their roles in development and disease. Most of our research centres on the heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 family of proteins.

RNA trafficking in the cytoplasm
Our initial experiments focussed on the molecular mechanism of trafficking of mRNAs in the cytoplasm of oligodendrocytes. In a series of papers, we described the protein (trans-acting factor) responsible for RNA trafficking and defined the minimum required cis-acting RNA element or motif (the A2RE). The same cis/trans pair of molecules was found in 2003 (Shan et al., J. Neurosci.) to transport A2RE-containing mRNAs to dendritic spines. This is still one of the best understood cytoplasmic mRNA transport pathways and is very important because the hnRNPs that are associated with trafficking granules appear to also be involved in memory formation and maintenance.

hnRNP A/B proteins in cancer
RNA trafficking is just one of the roles for the multi-tasking hnRNP A2/B1 proteins. They also participate in packaging of nascent RNA, the regulation of alternative splicing of RNA, and in maintenance of telomeres. We have shown that hnRNPs A2 and A3 recognize the ssDNA repeat in the G-rich strand of mammalian telomeres (binding it at the A2RE site) and the RNA template of telomerase, the enzyme which maintains the length of telomeres, Increasing telomerase activity and thus telomere length favours cell survival. Over-expression of certain of the hnRNP A2/B1 proteins enhances cell proliferation and cancer. One hnRNP A2/B1 isoform, B1 is upregulated in several cancers, including non-small-cell lung cancer. On the contrary, we have also used shRNA to examine the effects of suppression of hnRNP expression in mammalian cells and in Zebrafish (using morpholinos).

Structure/function relationships
We are using NMR spectroscopy and X-ray crystallography to determine the 3D structure of hnRNP A2 and its complexes with A2RE, the ssDNA telomere repeat and the A2-binding element of telomerase RNA.

In summary, the hnRNPs regulate many of the normal pathways in which RNA participates (e.g. RNA packaging and splicing, memory formation, telomere maintenance) and, not surprisingly, they are key players in many diseases (e.g. cancer, Alzheimer’s Disease, ALS).

Collaborators

Prof. H. Tiedge (SUNY, State University of New York)
Prof. Jeff Gorman (QIMR)
Prof. John Carson (University of Connecticut, Farmington)
Assoc. Prof. Derek Kennedy (Griffith University)
Prof. Elisa Barbarese (University of Connecticut, Farmington)

Funded Projects: 

I have been instrumental in obtaining (directly or indirectly) many major and vital items of equipment for the School in recent years, including multiple mass spectrometers, a surface plasmon resonance biosensor, a circular dichroism spectrometer, and a confocal microscope (totalling over $5 million).

NHMRC Project Grant 2010-2011
The contribution of upstream open reading frames to the eukaryotic proteome
(J Rothnagel, R W Smith, T Huber, J Gorman, A Nouwens, X Wang)
Total value of grant: $192,500

Queensland Cancer Fund 2007-2010
Heterogeneous nuclear ribonucleoprotein roles in alternative RNA splicing and human disease (R Smith and J Rothnagel)

Teaching: 
  • Introductory biochemistry for vet and science students (BIOC1011)
  • Cell structure and function - biological membranes (BIOL2200)
  • Neuroscience – particularly neuron and glial cell biology (NEUR3001)
  • Binding of proteins to DNA and RNA to proteins (BIOC3000)
  • Advanced Biomedical Sciences for Dentistry (DENT2052)
  • Advanced proteomics – mass spectrometry  (postgraduate)
Significant Professional Activities and Awards: 

Currently Queensland State Representative for The Australian Society for Biochemistry and Molecular Biology (ASBMB).

UQ Award for Excellence in Postgraduate Research Supervision. I have been Principal Supervisor for over 30 PhD students and I have been, or am, the Associate Supervisor for many more.

Member of the Neuroscience Society (international), the Queensland Protein Group, The Australia and New Zealand Society for Cell and Developmental Biology, and the ASBMB.

Elected Queensland State Representative for ASBMB.

Selected Publications: