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Joe Rothnagel

Associate Professor
Department of Molecular Bio-sciences
The University of Queensland
Australia

Biography

I completed my PhD in Biochemistry in 1985 at The University of Adelaide under the supervision of Professor George Rogers. From November 1985 - September 1988 I was a Visiting Fellow at the National Institutes of Health (Bethesda) in Dr Peter Steinert’s lab (NCI - Dermatology Branch). In September 1988, I joined Dr Dennis Roop at Baylor College of Medicine (Houston) as an Assistant Professor in the Department of Cell Biology chaired by Professor Bert O’Malley. During this time at Baylor, I was also an Assistant Professor in the Department of Dermatology. I returned to Australia in June 1995 as a lecturer in Biochemistry at The University of Queensland and was awarded a Wellcome Senior Research Fellowship in 1996.

Research Interest

Characterisation of novel bioactive peptides The difference between proteome complexity and gene number has confounded biologists. This difference can be accounted for in part by alternative transcription start sites, alternadiagramtive splicing, mRNA editing and post-translational modifications. However, we propose that the proteome also contains peptides arising from the translation of short open reading frames (sORFs) present within transcribed regions of the genome. Most translatable sORFs occur in the 5' untranslated regions (5'UTRs) of eukaryotic mRNAs but recent work has shown that they can be found within the main ORF and 3'UTR of mRNAs as well as on non-coding and antisense transcripts. The short peptides (sPEPs) encoded by sORFs may form the basis of a hitherto unknown regulatory network. Current research projects include: Discovery of sORFs and their encoded sPEPs using proteogenomic approaches (with Ross Smith & Amanda Nowens) Characterisation of novel bioactive peptides encoded by sORFs in mammalian cells and tissues Characterisation of novel bioactive peptides from plants and fungi (with Bernie Carroll & James Fraser) Development of bioinformatic tools to discover and characterise sORFs (with Scott Beatson) Development of the next generation of gene expression systems A second focus of this laboratory is directed towards the development of new eukaryotic expression vectors. We are investigating the role of post-transcriptional mechanisms in gene expression. This work has led to the development of short cis-acting sequencesGene Dimmer trade mark based on small upstream open reading frames (uORFs) that can be used to modulate gene expression; known as GeneDimmerTM and GeneBooster respectively. Both GeneDimmerTM and GeneBooster expression vectors will ultimately be used in cell biology, gene therapy and agriculture. Current research projects include: Development of second generation GeneDimmerTM vectors and their characterisation in mammalian cell lines Development of plant-specific GeneDimmerTM vectors and their characterisation in transgenic plants (with Bernie Carroll) Molecular genetics and cellular biology of the integument We maintain an interest in cutaneous biology and are studying the contribution of individual genes and proteins to skin development, differentiation and maintenance. Our research into the molecular mechanisms that regulate these processes is ultimately aimed at improving the treatment of inherited and acquired skin diseases such as eczema, psoriasis, cancer and accidental trauma such as burns, using gene and stem cell therapies. The skin also serves as an important model for other epithelia such as the gut, oral cavity, breast and prostate. Current research projects include: Analysis of polymorphisms in key skin and hair genes and their contribution to phenotype The characterisation of RNA-binding proteins (with Ross Smith) Funded Projects: UWA-UQ Bilateral Research Collaboration Award 2013 Development of a nucleolus-homing peptide for targeting RNA-therapeutics in gene therapy Total value of grant: $19,300 NHMRC Project Grant 2010-2012 The contribution of upstream open reading frames to the eukaryotic proteome Total value of grant: $192,500 National Rosacea Society 2009-2010 The role of tissue kallikreins in Rosacea Total value of grant: $21,934

Publications

  • Skarshewski, Adam, Stanton-Cook, Mitchell, Huber,ET AL.(2014) uPEPperoni: an online tool for upstream open reading frame location and analysis of transcript conservation. BMC Bioinformatics, 15 36: 1-6.

  • Andrews, Shea J. and Rothnagel, Joseph A. (2014) Emerging evidence for functional peptides encoded by short open reading frames. Nature Reviews: Genetics, 15 3: 193-204

  • Lukowski, Samuel W., Rothnagel, Joseph A. and Trezise,ET AL.(2014) CFTR mRNA expression is regulated by an upstream open reading frame and RNA secondary structure in its 5' untranslated region. Human Molecular Genetics, 24 4: 899-912.

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