Dr Brett Hamilton

Imaging Mass Spectrometr Specialist

Centre for Microscopy and Microanalysis
Faculty of Science

Overview

My PhD, conferred in 2003 by the University of Queensland (UQ), was undertaken under the guidance of Prof. Richard Lewis (IMB), A/Prof. Barry Chiswell (UQ, Chemistry), and Prof. Michael Moore (UQ, ENTOX), on the topic of Ciguatoxins, which are extremely potent site 5 sodium channel activators present in ciguatoxic fish. Their isolation and identification represented a challenging and rewarding PhD. The most innovative aspect of my research was the development of an approach involving radiolabelled receptor binding assays and LC-MS analyses that resulted in the discovery of a new family of ciguatoxins in the Indian ocean.

In 2002, I worked for Dr Kevin James at Cork Institute of Technology (CIT) as a full-time researcher, with responsibility for the maintenance, and training of personnel to use triple quadrupole and quadrupole time-of-flight mass spectrometers. I was also responsible for delivery of an instrumentational analytical chemistry course to undergraduate chemistry students. Whilst at this post I was involved in projects that investigated the fragmentation pathways of a myriad of phycotoxins, mycotoxins, and cyanobacterial toxins using mass spectrometry. These studies resulted in a number of publications in leading discipline journals including the Journal of Mass Spectrometry and Rapid Communications in Mass Spectrometry. The results of these structural studies were then applied to develop sensitive and specific quantitative assays for the routine detection of these compounds resulting in publications in Analytical Chemistry. Many of the assays developed translated to have significant impact on the Irish economy, through their adoption in establishing when it was safe to harvest and sell mussels. Dr James provided an encouraging environment to post-doctoral employees, and whilst there I wrote and submitted a number of successful research grant applications, and a received an Irish Post-Doctoral Fellowship.

In 2006 I moved back to Australia to work for Prof. Jeffrey Gorman at Queensland Institute for Medical Research (QIMR). I was principally recruited to establish a suite of electrospray mass spectrometers within Prof. Gorman’s new laboratory and facilitate proteomic analysis on these systems. At QIMR, Prof Gorman acquired the first LTQ-Orbitrap mass spectrometer in the country, along with the first ion trap equipped fitted with electron-transfer dissociation capabilities.

In 2008, I was recruited by Prof. Deon Venter to the Mater Hospital (in Brisbane), specifically to work for him as a part of the CRC for Biomarker Translation. The CRC project entailed establishing matrix-assisted laser desorption ionisation (MALDI) imaging and proteomics to investigate various breast cancer classes, and ovarian cancer. In collaboration, with Prof. Glenn King, Dr Eivind Undheim and A/Prof. Bryan Fry (U. Queensland), I have been involved with developing protocols to allow MALDI imaging of spider and centipede venom glands. A great deal of effort was involved in producing a suitable fixation approach that preserved the tissue without cross linking the peptides and proteins. Many parts of this work have been published, and presented at numerous conferences. The current optimised protocols allow us to routinely produce MALDI imaging data from serial sections cut from processed spider and centipede samples.

In 2017, I was recruited by Prof. Roger Wepf (UQ, CMM), and Prof. Ian Brereton (UQ, CAI), to come to work at the University of Queensland. As a part of this recruitment the Imaging Mass Spectrometry facility was transferred from the Mater Hospital to CMM/CAI at the University of Queensland (St Lucia campus). The move from the Mater involved relocation of the capabilities from an individual research group into an environment where the facility could be accessed by a much wider user base in accordance with CMM and CAI operating principles. The Imaging Mass Spectrometry facility at UQ can be accessed on a 24 hr/7 day basis for all users who have been trained to use the equipment.

Research Impacts

The number of publications since 2002, which include my PhD papers, is 38. My primary interest has been the application of mass spectrometry to various biological problems, most recently in a spatially resolved context. Currently my H index is 21, with an average citation rate of 30 citations per article. During the last 2 years, publications I have been involved with have been cited at a rate of close to 150 citations per year. During the last couple of years more of the projects I have been involved with have been published in higher impact journals such nature communications (DOI: 10.1038/ncomms4521), science advances (DOI: 10.1126/sciadv.aau4640). The work that I performed during my PhD and published in the lower impact journal, Toxicon (DOI: 10.1016/j.toxicon.2009.06.007 and 10.1016/S0041-0101(01)00259-8) are still quite highly cited because the published articles defined a new family of ciguatoxins and the first identification of ciguatoxin in human tissue sample associated with a fatality.

A number of the analytical methods developed at Cork Institute of Technology, under the guidance of Dr Kevin James, are still highly cited. Much of this work was published in journals such as Journal of Chromatography A, Toxicon, Rapid Communications in Mass Spectrometry, Analytical Chemistry, and the International Journal of Mass Spectrometry. Some of the approaches developed are still being used by regulators in Ireland today, allowing in many cases the replacement of mouse bioassay with more specific, targeted and humane methods of routine testing for a variety of analyte classes.

During my time at QIMR a couple of significant papers were published while I worked for Prof Jeffrey Gorman at QIMR, namely the post-translational modification work we undertook using the LTQ-Orbitrap and Ultraflex III looking at the Notch and hypoxia signaling pathways (DOI: 10.1073/pnas.0711591105), and hookworm secreted proteome analysis (DOI: 10.1074/mcp.M800206-MCP200).

During my time at the Mater, working for Prof Deon Venter, much time was spent developing Mass Spectrometry Imaging (MSI). The most cited and impactful work from this time was the cone snail predation and defensive story, which was published in nature communications with PI Lewis (DOI: 10.1038/ncomms4521) and really has changed the paradigm in the cone snail field – especially in the context of deciphering the predatory components from the defensive components. Possibly the most impactful paper we have produced in the IMS field describes how we developed a new sample preparation protocol to enable aldehyde free fixation of delicate venom gland samples, which enabled both the preservation of the samples and the ability to product protein and peptide IMS data. The first paper describing this workflow was published with Dr Eivind Undheim and Prof Glenn King in PNAS (DOI: 10.1073/pnas.1424068112) describing its application the centipede venom glands.

After moving the IMS facility in 2017 from the Mater to the CMM at UQ, I have been facilitating access to the facility in addition to maintaining existing and establishing new collaborations in the Imaging Mass Spectrometry space. Once the facility more functioning after move, I have been activity recruiting researchers to come and use the instruments to assist various research projects. To-date, since late 2017 I have been involved in 7 published articles, with a number more under review or preparation. One of these articles was published in science advances, describing the venom of the giant bullant (Myrmecia gulosa) Sci Adv. 2018 Sep; 4(9): eaau4640. We have a manuscript under review which emanates from a collaboration between myself, Dr Eivind Undheim, CI Blanksby and Dr David Marshall.

Qualifications

  • Doctor of Philosophy, The University of Queensland
  • Bachelor of Science (Honours), The University of Queensland
  • Bachelor of Science, The University of Queensland

Publications

View all Publications

Publications

Book Chapter

Journal Article

Conference Publication

  • Griffin, Paul, Price, Gareth, Hamilton, Brett, Schooneveldt, Jacqueline, Urbanski, Tess, Schlebusch, Sanmarie and Venter, Deon (2013). Rapid Identification of Vancomycin Resistant Enterococci with Maldi-Tof Mass Spectrometry. In: Abstracts for the RACP Future Directions in Health Congress 2013. The Royal Australasian College of Physicians Future Directions in Health Congress 2013 (RACP), Perth WA, Australia, (27-27). 26-29 May 2013. doi:10.1111/imj.12153

  • Morgenstern, David, Hamilton, Brett, Sher, Daniel, Jones, Alun, Mattius, Gideon, Zlotkin, Eli, Venter, Deon and King, Glenn F. (2012). The bio-logic of venom complexity. In: 17th World Congress of the International Society on Toxinology & Venom Week 2012, 4th International Scientific Symposium on All Things Venomous, 17th World Congress of the International Society on Toxinology & Venom Week 2012, 4th International Scientific Symposium on All Things Venomous. 17th World Congress of the International-Society-on-Toxinology (IST)/Venom Week/4th International Scientific Symposium on All Things Venomous, Honolulu, Hawaii, United States, (241-242). 8-13 July 2012. doi:10.1016/j.toxicon.2012.04.285

  • Canás, Isa Ruppen, O'Callaghan, Keith, Moroney, Cian, Hamilton, Brett, James, Kevin J. and Furey, Ambrose (2010). The development of a rapid method for the isolation of four azaspiracids for use as reference materials for quantitative LC-MS-MS methods. In: , , (1477-1491). . doi:10.1007/s00216-010-4007-y

  • Furey, Ambrose, Crowley, Janet, Hamilton, Brett, Lehane, Mary and James, Kevin J. (2005) Strategies to avoid the mis-identification of anatoxin-a using mass spectrometry in the forensic investigation of acute neurotoxic poisoning. Journal of Chromatography A, 1082 1: 91-97. doi:10.1016/j.chroma.2005.05.040

  • Hamilton, Brett, Sierra, Mónica Díaz, Lehane, Mary, Furey, Ambrose and James, Kevin J. (2004). The fragmentation pathways of azaspiracids elucidated using positive nanospray hybrid quadrupole time-of-flight (QqTOF) mass spectrometry. In: , , (355-362). . doi:10.1155/2004/949018

  • Hamilton, B., Lewis, R., Chiswell, B., Moore, M. and Jones, A. (1999). Development of analytical detection methodologies of ciguatoxins. In: Proceedings of 6th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology. 6th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology, Cairns, (). 13th - 17th September, 1999.