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Personal profile

Research interests

My research focuses on the molecular interactions that take place in human cells in human and viral RNA biology, innate immunity and cellular signalling.

The laboratory, run jointly with A/Prof Matthew Wilce, aims to better understand molecular recognition by determining the overall shapes, as well as the precise three-dimensional structures of macromolecular complexes and by testing their affinity and specificity using biophysical techniques. We investigate several molecular systems involved in RNA biology, innate immunity and cancer cell progression. These include the study of proteins which bind to mRNA and regulate translation, proteins which recognise RNA in innate immunity and the development of peptides which inhibit cancer cell proliferation and migration.

Current Research Projects

Protein-RNA interactions in antiviral cellular defence and inflammation

Protein-RNA interactions are integral to cellular biology – both in normal cellular function and also in cells subject to the stresses of viral invasion. Proteins are responsible for the detection of viral RNA, and initiation of the innate immune response. Proteins direct post-transcriptional regulation of cytokines produced as a result of cellular stress, and are responsible for preventing their over-expression. In some cases, cellular proteins that normally function in translational control are hijacked by viral RNA as part of the viral mechanism of replication in the cell. Underlying each of these types molecular events are intricate and specialised molecular interactions. Their understanding would greatly advance our knowledge of antiviral cellular defence and potentially lead to new means to combat virus-related disease and inflammatory disorders.

Our lab has specialised in the study of protein-RNA interactions, using biophysical and structural tools to better understand the basis for their affinity, specificity and conformational consequences underlying their mechanism of action. Our objective is to delineate specific protein-RNA systems relevant to antiviral cellular defence.

 

 

Biography

I completed a B. Sc (Hons) degree at Monash University, specialising in novel peptide chemistries at honours level. In 1994 I graduated with a Ph.D. in Medicinal Chemistry from the Victorian College of Pharmacy (now MIPS, Monash University) in the field of NMR structural and dynamics studies of peptides and proteins. I then took up a position at Queensland University in the Centre for Drug Design and Development with Professor David Craik, synthesising proteins using peptide and novel linkage chemistries. I then spent several years at the University of Sydney with Professor Glenn King, extending my expertise to include molecular biological and protein expression and purification techniques as well as 3D heteronuclear NMR spectroscopy and analytical ultracentrifugation. Here I began to develop an interest in structural and dynamic studies of novel cancer targets as well as the use of peptides for transporting bioactive compounds across cell walls. I also embarked on structural studies of a protein:DNA complex involved in replication fork arrest for which I was awarded an ARC Postdoctoral Fellowship. In 1999 I established my own laboratory as a joint member of Biochemistry and Chemistry at the Department at the University of Western Australia, where I extended my research into the field of structural and dynamic studies of protein-RNA interactions involved in mRNA stabilization in collaboration with partner, Prof Matthew Wilce. In 2001 I was awarded an ARC Fellowship to pursue molecular interactions studies, and have added surface plasmon resonance and isothermal titration calorimetry to the repertoire of biophysical techniques that underpins the work. In 2005 I moved with Matthew Wilce to Monash University to establish labs in the dynamic Department of Biochemistry and Molecular Biology. I was appointed as a Senior lecturer in 2007 and promoted to Associate Professor in 2010. I now engage in both teaching and research in the macromolecular sciences.

Monash teaching commitment

I currently teach into the following units:

BMS1011, BCH3031, BMS3031, BMS2062, BCH3052

Keywords

  • Protein-RNA Interactions
  • Structural Biology
  • Protein Chemistry
  • Peptides
  • Cancer And Immunity

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Projects 2001 2022

Research Output 1996 2018

Combined roles of ATP and small hairpin RNA in the activation of RIG-I revealed by solution-based analysis

Shah, N., Beckham, S. A., Wilce, J. A. & Wilce, M. C. J., 6 Apr 2018, In : Nucleic Acids Research. 46, 6, p. 3169-3186 18 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
File

Preparation and cellular uptake of bicyclic‐peptide cargo clicked to cell penetrating peptides

Kulkarni, K., Watson, G. M., Sang, J. & Wilce, J. A., May 2018, In : Journal of Peptide Science. 110, 3, 11 p., e24037.

Research output: Contribution to journalArticleResearchpeer-review

The TRIM-NHL protein NHL-2 is a co-factor in the nuclear and somatic RNAi pathways in C. Elegans

Davis, G. M., Tu, S., Anderson, J. WT., Colson, R. N., Gunzburg, M. J., Francisco, M. A., Ray, D., Shrubsole, S. P., Sobotka, J. A., Seroussi, U., Lao, R. X., Maity, T., Wu, M. Z., McJunkin, K., Morris, Q. D., Hughes, T. R., Wilce, J. A., Claycomb, J. M., Weng, Z. & Boag, P. R., 21 Dec 2018, In : eLife. 7, 29 p., e35478.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
File

Discovery, Development, and Cellular Delivery of Potent and Selective Bicyclic Peptide Inhibitors of Grb7 Cancer Target

Watson, G. M., Kulkarni, K., Sang, J., Ma, X., Gunzburg, M. J., Perlmutter, P., Wilce, M. C. J. & Wilce, J. A., 22 Nov 2017, In : Journal of Medicinal Chemistry. 60, 22, p. 9349-9359 11 p.

Research output: Contribution to journalArticleResearchpeer-review

Huntingtin Inclusions Trigger Cellular Quiescence, Deactivate Apoptosis, and Lead to Delayed Necrosis

Ramdzan, Y. M., Trubetskov, M. M., Ormsby, A. R., Newcombe, E. A., Sui, X., Tobin, M. J., Bongiovanni, M. N., Gras, S. L., Dewson, G., Miller, J. M. L., Finkbeiner, S., Moily, N. S., Niclis, J., Parish, C. L., Purcell, A. W., Baker, M. J., Wilce, J. A., Waris, S., Stojanovski, D., Böcking, T. & 4 othersAng, C-S., Ascher, D. B., Reid, G. E. & Hatters, D. M., 2 May 2017, In : Cell Reports. 19, 5, p. 919-927 9 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
File

Activities 2010 2015

  • 2 Submissions to industry or govt committees, commissions and inquiries

Current Co-chair

Jackie Wilce (Member)
27 Oct 20151 Nov 2019

Activity: External Academic EngagementSubmissions to industry or govt committees, commissions and inquiries

Committee member

Jackie Wilce (Member)
5 Feb 20107 Feb 2018

Activity: External Academic EngagementSubmissions to industry or govt committees, commissions and inquiries