In 1994, Marc Wilkins developed the concept of the proteome and coined the term. In 1997 he co-wrote and co-edited the first book on proteomics (4,000+ copies sold). This, and a series of other seminal works, substantially contributed to the establishment of the proteome and of proteome research. Proteomics is now widely adopted, is included in biochemistry textbooks and is part of the undergraduate curriculum.
Marc has published >200 peer-reviewed research papers, review papers and book chapters and has edited 2 books. Marc's research has tackled many of the key issues in proteomics. A particular strength has been the capacity to combine large-scale analytical techniques with complex bioinformatics to open new avenues for biological investigation. Current research interests are (i) the role of protein methylation in the proteome (ii) the dynamics of protein interaction networks, studied with crosslinking mass spectrometry. Marc is also an active researcher in genomics and transcriptomics, where his extended team has technical expertise in next-generation sequencing and the bioinformatic analysis of resulting data. Recent highlights include the koala genome project. You can find all Marc's publications and citations here.
Marc directs two centres at UNSW: the NSW Systems Biology Initiative and the Ramaciotti Centre for Genomics. These centres are or have been funded by NCRIS, EIF Super Science, ARC LIEF and the NSW State Government SLF and RAAP schemes.
Marc co-founded Proteome Systems Pty Ltd in 1999. Recently renamed to Tyrian Diagnostics, this proteomic diagnostics company was listed on the Australian Securities Exchange (ASX) and has developed technology for rapid point-of-care diagnostic testing . Marc is also a co-founder of Regeneus Pty Ltd, a regenerative medicine company which uses autologous adult stem cells to treat a range of musculoskeletal disorders. This company was listed on the ASX in 2013.
- 2016 - Executive Management, Genomics, Bioplatforms Australia
- 2011 - Director, Ramaciotti Centre for Genomics
- 2008 - Director, NSW Systems Biology Initiative
- 2005 - Professor of Systems Biology, UNSW
- 1999 - 2005 Vice President Bioinformatics then Head of Proteomics, Proteome Systems Limited
Honours and Awards
- Awarded a Doctor of Science (D. Sc.) in October 2017 for outstanding contributions to research in proteomics, post-translational modifications and protein interaction networks.
- ASBMB Beckman Coulter Discovery Science Award 2012 for distinguished contributions to the field of biochemistry and molecular biology.
- Elected as Council Member of the Human Proteome Organisation (HUPO) 2009-2011, 2011-2014, 2015-2018, 2019-2021.
- Senior Editor of Proteomics (2004-2013).
- Member of the Scientific Advisory Boards of the Integrated Materials Design Centre (IMDC, 2015-2017), EMBL Australia Bioinformatics Advisory Committee (2011-2015), Victorian Life Science Computational Initiative (VLSCI) (2009-2015), the Macquarie University Biomolecular Frontiers Centre of Research
Excellence (2009-), the NHMRC Australian Proteomics Computational Facility (APCF) (2007-2011) and the ARC Centre of Excellence in Bioinformatics (2006-2011).
- Contributions to policy in NSW State Government on the NSW Health Genomics Strategy (2018, 2019), the Australian National Genomics Policy framework (2017), New Zealand Government genomics research strategy (2017) and member of the Australian Government's Expert Task Force for Bioinformatics (2003-2005).
My research questions are centred around proteomics.
1. What is the regulatory network of histone methylation?
Histone methylation is a crucial process that affects the compaction and relaxation of chromatin, and thus gene expression in the cell. The sites of histone methylation are understood and the enzymes responsible are known, at least in the model system of yeast. However we know little about how the four 'writer' enzymes and the four 'eraser' enzymes are actually regulated and how they work as a single integrated system. We are exploring:
- Are the histone methyltransferases and demethylases phosphorylated?
- If phosphorylation on these enzymes affect their activity and if so, how?
- What kinases are responsible for this phosphorylation?
- Do the modification of writer and eraser enzyme control where they act, on chromatin in the genome?
We aim to connect the cell's signalling system with its histone-based system of gene regulation in this project.
The project is supported by ARC Discovery Project grant 2020: The Regulatory Network of Histone Methylating and Demethylating Enzymes.
Recent papers on protein methylation:
- Characterization of Protein Methyltransferases Rkm1, Rkm4, Efm4, Efm7, Set5 and Hmt1 Reveals Extensive Post-Translational Modification. Winter DL, Hart-Smith G, Wilkins MR. J Mol Biol. 2018 430(1):102-118.
- Methylation of Elongation Factor 1A: Where, Who, and Why? Hamey JJ, Wilkins MR. Trends Biochem Sci. 2018 43(3):211-223.
- METTL21B Is a Novel Human Lysine Methyltransferase of Translation Elongation Factor 1A: Discovery by CRISPR/Cas9 Knockout. Hamey JJ, Wienert B, Quinlan KGR, Wilkins MR. Mol Cell Proteomics. 2017 Dec;16(12):2229-2242.
2. How do cells make decisions via protein interaction networks?
Cells use protein post-translational modifications as an 'information management' and 'status management' system. Yet how this information is integrated, to make actual decisions inside networks, is poorly understood. We are exploring:
- How often are two post-translational modifications found next to each other in the proteome? Especially methylation, phosphorylation and acetylation?
- For modifications that are nearby, what is their 'logic' - do they block each other? Is one required before the other?
- Do nearby modifications form small 'decision making modules' in interaction networks?
- Do nearby modifications change the interaction choice of a protein? Or change its localisation in the cell?
The project is supported by ARC Discovery Project grant 2017: The discovery of decision-making modules in protein interaction networks.
Recent papers on crosstalk of post-translational modifications:
- Crosstalk of Phosphorylation and Arginine Methylation in Disordered SRGG Repeats of Saccharomyces cerevisiae Fibrillarin and Its Association with Nucleolar Localization. Smith DL, Erce MA, Lai YW, Tomasetig F, Hart-Smith G, Hamey JJ, Wilkins MR. J Mol Biol. 2020 432(2):448-466.
- Knockout of the Hmt1p Arginine Methyltransferase in Saccharomyces cerevisiae Leads to the Dysregulation of Phosphate-associated Genes and Processes. Chia SZ, Lai YW, Yagoub D, Lev S, Hamey JJ, Pang CNI, Desmarini D, Chen Z, Djordjevic JT, Erce MA, Hart-Smith G, Wilkins MR. Mol Cell Proteomics. 2018 17(12): 2462-2479.
3. How is the protein interactome regulated?
Recent, breakthroughs in crosslinking mass spectrometry (XL-MS) have made it possible to measure thousands of protein-protein interactions in a single sample. These generate a 'protein interactome' which reflects the biological state of a system, at a point in time. Use of heavy isotope-based techniques with XL-MS allows 'protein interactomes' to then be compared. We are exploring:
- The optimisation of techniques for XL-MS.
- The roles of gene expression and protein post-translational modifications in the regulation of the protein interactome.
- The role of alternate splicing of mRNA and resulting isoforms in regulating the protein interactome.
Recent papers on crosslinking mass spectrometry:
- Cross-linking Mass Spectrometry Analysis of the Yeast Nucleus Reveals Extensive Protein-Protein Interactions Not Detected by Systematic Two-Hybrid or Affinity Purification-Mass Spectrometry. Bartolec TK, Smith DL, Pang CNI, Xu YD, Hamey JJ, Wilkins MR. Anal Chem. 2020 92(2):1874-1882.
- Characterization of the Interaction between Arginine Methyltransferase Hmt1 and Its Substrate Npl3: Use of Multiple Cross-Linkers, Mass Spectrometric Approaches, and Software Platforms. Smith DL, Götze M, Bartolec TK, Hart-Smith G, Wilkins MR. Anal Chem. 2018 90(15):9101-9108.
I am always interested to have enthusiastic students join the lab!
Previous lab members include 33 honours students (including 6 who won the UNSW University Medal), 14 PhD students, 2 jointly supervised PhD students and 5 Masters by Research students
Students in my lab can obtain experience in the following areas:
- Wet lab - proteomics of protein methylation, regulation of histone and non-histone protein methyltransferases, proteome-scale crosslinking mass spectrometry for network generation, large-scale monitoring of changes in protein-protein interactions via crosslinking mass spectrometry
- Dry lab - bioinformatics tool development for proteomics, bioinformatics of next-generation sequencing (genome assembly, transcriptomics)
I am the Coordinator of BIOC3111 Molecular Biology of Proteins. I teach into 7 other undergraduate courses.