About Me

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 >260 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, and (ii) large-scale analysis of protein-protein interactions, studied with crosslinking mass spectrometry (XL-MS). Recent highlights, both published in P.N.A.S. describe the complete protein methylation network in yeast and the largest study to date of human protein-protein interactions and structure through use of XL-MS. 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. Highlights include the koala genome project, in Nature Genetics, and collaborative work in the RNA Atlas published in Nature Biotechnology. You can find all Marc's publications and citations here.

Marc leads an ARC-funded proteomics and systems biology lab (lab web site here). His group is part of the recently announced MACSYS ARC Centre of Excellence (announcement here), a 7 year $35M project. Marc is the UNSW node leader for this Centre. 

Marc was the Director of the Ramaciotti Centre for Genomics - the largest genomics facility at any Australian university, from 2011 to 2022. This Centre was funded by NCRIS, EIF Super Science, ARC LIEF and the NSW State Government SLF and RAAP schemes. A special highlight for the Centre was its analysis of >1,000,000 samples for the genomics community. 

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. 

Professional Experience

• 2022 - Deputy Dean (research and enterprise), Faculty of Science
• 2016 - 2022 Executive Management, Genomics, Bioplatforms Australia 
• 2011 - 2022 Director, Ramaciotti Centre for Genomics
• 2008 - 2022 Director, NSW Systems Biology Initiative (bioinformatics group)
• 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, 2022-2024.
• Elected to the Management Committee (ordinary member) of the Australasian Proteomics Society (2019-2021, 2022-2024). Organising committee of the society's annual conference. 
• Senior Editor of PROTEOMICS (2004-2013).
• Member of the Scientific Advisory Boards of the Macquarie University Biomolecular Discovery Research Centre (2019-), UNSW 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 (2009-2018), 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 (2018-2023), 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).

Research

We ask research questions about regulatory systems inside the eukaryotic cell. We use a combination of proteomics, genome editing and genetics, phenotypic screening and a range of standard biochemistry and molecular biology techniques in our work. 

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:

• The protein methylation network in yeast: A landmark in completeness for a eukaryotic post-translational modification. Hamey JJ, Wilkins MR. Proc Natl Acad Sci U S A. 2023 120(23):e2215431120.
• Differential Proteome and Interactome Analysis Reveal the Basis of Pleiotropy Associated With the Histidine Methyltransferase Hpm1p. Bartolec TK, Hamey JJ, Keller A, Chavez JD, Bruce JE, Wilkins MR. Mol Cell Proteomics. 2022 Jul;21(7):100249.
• Post-translational modification analysis of Saccharomyces cerevisiae histone methylation enzymes reveals phosphorylation sites of regulatory potential. Separovich RJ, Wong MWM, Chapman TR, Slavich E, Hamey JJ, Wilkins MR. J Biol Chem. 2021 Jan-Jun;296:100192.
• 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. Do post-translational modifications of ribosomes regulate translational specificity?

Ribosomal proteins carry quite extensive post-translational modifications, including methylation, acetylation, phosphorylation and ubiquitinylation. The role of these is very poorly understood, which is remarkable given the essential process of translation in the cell. We are exploring:

• What is the totality of modifications in the eukaryotic ribosome?
• When do these change?
• What is the function of the modifications?
• Do the modifications lead to a change in ribosomal specificity; especially a change in the mRNAs chosen for translation?

The project is supported by ARC Discovery Project grant 2022: The effect of methylation and phosphorylation on ribosome function.

3. Large-scale analysis of protein interactions and structure with crosslinking mass spectrometry

Recent, breakthroughs in crosslinking mass spectrometry (XL-MS) have made it possible to measure thousands of protein-protein interactions in a single sample, and also generate low-resolution measurements of structure for single proteins. The low-resolution measurements are very useful in association with AI-driven protein modelling. Together, these generate a 'protein interactome', and 'structural proteome', 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 and aspects of the structural proteome to 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 discovers, evaluates, and corroborates structures and protein-protein interactions in the human cell. Bartolec TK, Vázquez-Campos X, Norman A, Luong C, Johnson M, Payne RJ, Wilkins MR, Mackay JP, Low JKK. Proc Natl Acad Sci U S A. 2023 Apr 25;120(17):e2219418120. (this is an outstanding collaboration between our PhD student Tara Bartolec and ex-PhD student Jason Low).
• 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.

Supervision

I am always happy to have enthusiastic students join the lab! Meet some of our current lab members here. 

Previous lab members for whom I've had the pleasure to supervise include 38 honours students (6 who won the UNSW University Medal), 16 PhD students and 5 Masters by Research students. I have been a secondary supervisor to 7 higher degree 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)

Teaching

I teach into 8 undergraduate courses; most of my lecturing is into BIOC3111 (Molecular Biology of Proteins).