New South Wales Systems Biology Initiative

The New South Wales Systems Biology Initiative, directed by Marc Wilkins is a non-profit facility within the School of Biotechnology and Biomolecular Sciences at the University of New South Wales. Their focus is undertaking basic and applied research in the development and application of bioinformatics for genomics and proteomics.

Research conducted at the Systems Biology Initiative

Researchers at the facility are currently working on the following projects:

Methylation on the proteome of Saccharomyces cerevisiae

Modifications generate conditional effects on proteins, whereby their covalent attachment to amino acids will cause perturbation of a particular protein resulting in an impact on the potential interactions of its newly modified form.[1] Methylation is one of the most recognised post-translational modifications in histones for chromatin structure and gene expression.[2] It is also one of many modifications found on the short N-terminal regions of histones, which assemble to form the histone code, which regulates chromatin assembly and epigenetic gene regulation.[3] Identification of methylation across the interactome is poorly documented. Researchers at the System Biology Initiative have been identifying techniques to identify novel methylated lysine and arginine residues via mass spectrometry[4] and peptide mass fingerprinting.[5] Currently researchers are in the process of utilising these techniques to identify novel methylated residues in the Saccharomyces cerevisiae interactome.

Separation and identification of protein complexes

Large-scale analysis of protein complexes is an emerging difficulty as methods for the fractionation of protein complexes that are not compatible with downstream proteomic techniques. The Systems Biology Initiative is utilising the technique of blue native continuous elution electrophoresis (BN-CEE).[6] This method generates liquid-phase fractions of protein complexes. The resulting complexes can be further analysed by polyacrylamide gel electrophoresis and mass spectrometry. This will help identify the constituent proteins of many complexes. Currently researchers are employing this technique on the Saccharomyces cerevisiae cellular lysate.

Visualising proteins, complexes and interaction networks

The integration of biological data, including protein structures, interactions etc. can be generated through automated technology. The importance of such data can often be lost without proper visualisation of the data. The Systems Biology Initiative is currently working on an adaptation of the Skyrails Visualisation System. This system, called the interactonium uses a virtual cell for the visualisation of the interaction network, protein complexes and protein 3-D structures of Saccharomyces cerevisiae.[7] The tool can display complex networks of up to 40 000 proteins or 6000 multiprotein complexes. The Interactorium permits multi-level viewing of the molecular biology of the cell. The Interactorium is available for download.[8]

References

  1. Wilkins MR, Kummerfeld SK (May 2008). "Sticking together? Falling apart? Exploring the dynamics of the interactome". Trends in Biochemical Sciences. 33 (5): 195–200. doi:10.1016/j.tibs.2008.03.001. PMID 18424047.
  2. Fischle W, Tseng BS, Dormann HL, et al. (December 2005). "Regulation of HP1-chromatin binding by histone H3 methylation and phosphorylation". Nature. 438 (7071): 1116–22. doi:10.1038/nature04219. PMID 16222246.
  3. Strahl BD, Allis CD (January 2000). "The language of covalent histone modifications". Nature. 403 (6765): 41–5. doi:10.1038/47412. PMID 10638745.
  4. Couttas TA, Raftery MJ, Bernardini G, Wilkins MR (July 2008). "Immonium ion scanning for the discovery of post-translational modifications and its application to histones". Journal of Proteome Research. 7 (7): 2632–41. doi:10.1021/pr700644t. PMID 18517236.
  5. Pang CN, Gasteiger E, Wilkins MR (2010). "Identification of arginine- and lysine-methylation in the proteome of Saccharomyces cerevisiae and its functional implications". BMC Genomics. 11: 92. doi:10.1186/1471-2164-11-92. PMC 2830191. PMID 20137074.
  6. Huang KY, Filarsky M, Padula MP, Raftery MJ, Herbert BR, Wilkins MR (May 2009). "Micropreparative fractionation of the complexome by blue native continuous elution electrophoresis". Proteomics. 9 (9): 2494–502. doi:10.1002/pmic.200800525. PMID 19343713.
  7. Widjaja YY, Pang CN, Li SS, Wilkins MR, Lambert TD (December 2009). "The Interactorium: visualising proteins, complexes and interaction networks in a virtual 3-D cell". Proteomics. 9 (23): 5309–15. doi:10.1002/pmic.200900260. PMID 19798670.
  8. "Downloads: The Interactorium". New South Wales Systems Biology Initiative.
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