Infectious Disease Responses Laboratory
Spanning the themes of Infectious Disease, Immunity & Inflammation and Cancer in Medicine at UNSW, our research involves the molecular identification and subtyping of viral pathogens such as influenza and HCV, understanding their biological properties and mode of action at the molecular level, and the development of antivirals to respond to their infection. The technological approaches we develop allow us to characterise viruses (including oncoviruses) into different subtypes, develop specific treatments, and also help advance ‘omics’ and informatics approaches for their use in clinical practice.
A current research focus concerns the development and application of molecular based methods, particularly mass spectrometry, to improve the identification, characterization and responses to viruses that cause infectious disease and cancer. A particular focus has been to arrest the impact of the influenza virus. Influenza is responsible for as many or more deaths in Australia today than most individual causes of human cancers, with the exception of lung cancer. Furthermore, an estimated 15 percent of all human cancers worldwide are associated with viral infections. Improving our ability to identify and respond to such disease causing viruses is essential to reducing their burden on public health.
Recent work has involved the identification and development of new antiviral inhibitors to combat viruses associated with influenza and hepatitis by exploring their mode of action using experimental and computational approaches. We have also developed a new phylogenetics approach (known as phylonumerics) to improve our ability to study and better understand the evolution of viruses, with a view to reducing their impact. Innovative new mass spectrometry based methods and bioinformatics approaches and computer algorithms have been developed and employed to characterise influenza viruses, and other biopathogens, at the molecular protein level without sequencing.
A new structural biology approach employing a protein footprinting technology (also known by the acronym RP-MS) has also been developed in collaboration and applied to study proteins and complexes important to human vision. The impact of early onset oxidative damage on their structural integrity associated with cataract, a leading cause of blindness worldwide, has been investigated.
Head & Group Leader
Professor Kevin Downard has held professorial positions abroad and in Australia after completing postdoctoral studies and holding a subsequent academic position at the Massachusetts Institute of Technology. He has over 30 years research experience, the past 24 years leading his own group to advance discoveries in science and medicine.
Professor Downard is the author of over 110 peer-reviewed scientific publications, as well as two books, and he has received large research funding from the Australian Research Council and other sources. He has twice received international fellowships from both the Australian Academy of Science and the Japan Society for the Promotion of Science and is frequently invited to give keynote lectures at national and international conferences. He was the first Australian to be recognised for his research achievements with a faculty award from the world's largest mass spectrometry society (ASMS), of which he is a 25+ year member. He convened both the largest Australian biennial MS conference in 2009 and the 2003 Sir Mark Oliphant Conference in Sydney. He has also been recognised by the Australian Academy of Science for his efforts to research and document the history of science as recipient of the Moran Award in 2006. In 2016, he received the annual award at the British Biological Mass Spectrometry Symposium in London.
He collaborates with researchers at UNSW, greater Sydney, nationally and internationally in both academia and industry.
Downard KM (2021) Protein Phylogenetics with Mass Spectrometry. A Comparison of Methods, Anal. Methods, in press.
Akand EH, Downard KM (2021) Evolution of Type B Influenza Virus using a Mass Spectrometry Based Phylonumerics Approach, Evol. Biol. in press. https://dx.doi.org/10.1007/s11692-021-09535-z
Dollman NL, Griffin JH, Downard KM (2020) Detection, Mapping and Proteotyping of SARS CoV-2 Coronavirus with High Resolution Mass Spectrometry, ACS Infect. Dis., 6: 3269-3276. https://dx.doi.org/10.1021/acsinfecdis.0c00664
Downard KM (2020) Sequence Free Phylogenetics with Mass Spectrometry, Mass Spectrom. Rev., in press. https://doi.org/10.1002/mas.21658
Downard (2020) Darwin's Tree of Life is Numbered. Resolving the Origins of Species by Mass, Evol. Bio., 47: 325-333.. https://doi.org/10.1007/s11692-020-09517-7
Akand EH, Downard KM (2020) Reimaging the Tree of Life using a Mass Based Phylonumerics Approach, Evol. Biol., 47: 76–84. https://doi.org/10.1007/s11692-020-09490-1
Downard KM (2020) Mass-based Protein Phylogenetic Approach to Identify Epistasis, in Methods in Molecular Biology: Epistasis - Methods and Protocols (Ed. K-C Wong), Vol. 2212, Ch. 1, pp. 1-17. https://www.springer.com/gp/book/9781071609460https://www.springer.com/gp/book/9781071609460
Akand EH, Downard KM (2019) Mechanisms of Antiviral Resistance in Influenza Neuraminidase Revealed by a Mass Spectrometry Based Phylonumerics Approach, Mol. Phylogen. Evol. 135: 286-296. https://doi.org/10.1016/j.ympev.2019.03.009
Downard KM (2019) Concentration of Hydroxyl Radicals during Electrical Discharge for Radical Probe Protein Footprinting Mass Spectrometry, Rapid Commun. Mass Spectrom., 33: 1420-1422. https://doi.org/10.1002/rcm.8484
Maleknia SD, Downard KM (2019) Protein Footprinting with Radical Probe Mass Spectrometry - Two Decades of Achievement, in Current Perspectives on Footprinting as a Tool for Structural Biology (ed. Ralston CY), Protein Peptide Letters, 26(1): 4-15. https://doi.org/10.2174/0929866526666181128124241
Downard KM (2019) A Molecular Immunoproteomics Approach to Assess the Viral Antigenicity of Influenza, in Methods in Molecular Biology: Immunoproteomics, Vol. 2024, 2nd edition (Ed. S. Twine & K. Fulton), Ch. 24, pp. 353-369. https://doi.org/10.1007/978-1-4939-9597-4_24
Downard KM, Maleknia SD (2019) Mass Spectrometry in Structural Proteomics: The Case for Radical Probe Protein Footprinting, Trends in Anal. Chem., 110: 293-302. https://doi.org/10.1016/j.trac.2018.11.016
Akand EH, Downard KM (2018) Ancestral and Compensatory Mutations that Promote Antiviral Resistance in Influenza N1 Neuraminidase Revealed by a Phylonumerics Approach, J. Mol. Evol., 86(8): 546-553. https://doi.org/10.1007/s00239-018-9866-4
Uddin R, Downard KM (2018) Molecular Basis of Benzimidazole Inhibitors to Hepatitis C Virus Envelope Glycoprotein, Chem. Biol. Drug Design, 92(3): 1638-1646. (cover article) https://doi.org/10.1111/cbdd.13329
Akand EH, Downard KM (2018) Identification of Epistatic Mutations and Insights into the Evolution of the Influenza Virus Using a Mass-Based Protein Phylogenetic Approach, Mol. Phylogenet. Evol., 121: 132-138. http://dx.doi.org/10.1016/j.ympev.2018.01.009
Cody RB, Tamura J, Downard KM (2018) Quantitation of Anthocyanins in Elderberry Fruit Extracts and Nutraceutical Formulations with Paper Spray Ionization Mass Spectrometry, J. Mass Spectrom., 53: 58-64. http://dx.doi.org/10.1002/jms.4033
Akand EH, Downard KM (2017) Mutational Analysis Employing a Phylogenetic Mass Tree Approach in a Study of the Evolution of the Influenza Virus, Mol. Phylogenet. Evol., 112: 209-217. http://dx.doi.org/10.1016/j.ympev.2017.04.005
Uddin R, Downard KM (2017) Subtyping of Hepatitis C Virus with High Resolution Mass Spectrometry, Clin. Mass Spectrom., 4-5: 19-24. http://dx.doi.org/10.1016/j.clinms.2017.08.003
Ma S, Downard KM, Wong JWH (2017) Phylogenetic Analysis using Protein Mass Spectrometry, in Methods in Molecular Biology: Proteome Bioinformatics (eds. Mathivanan S, Keerthikumar S), Humana Press, NJ USA, pg. 135-146. (ISBN 978-1-4939-6738-4). http://www.springer.com/gp/book/9781493967384
Akashi S, Downard KM (2016) Effect of Charge on the Conformation of Highly Basic Peptides including the Tail Regions of Histone Proteins by Ion Mobility Mass Spectrometry, Anal. Bio. Chem., 408: 6637-6648. http://dx.doi.org/10.1007/s00216-016-9777-4
Maleknia SD, Downard KM (2016) New Anthocyanins from Black Elderberry of Inhibitory Potential Revealed by Mass Spectrometry, Nat. Prod. J., 6: 94-102. http://dx.doi.org/10.2174/2210315506666160115214231
Downard KM (2016) Indirect Study of Non-Covalent Protein Complexes by MALDI Mass Spectrometry. Origins, Advantages and Applications of the "Intensity-Fading" Approach, Mass Spectrom. Rev., 35: 559-573. http://dx.doi.org/10.1002/mas.21480
Lu R, Müller P, Downard KM (2015) Molecular Basis of Influenza Hemagglutinin Inhibition with an Entry-Blocker Peptide by Computational Docking and Mass Spectrometry, Antivir. Chem. Chemother., 24(3-4): 109-117. http://dx.doi.org/10.1177/2040206615622920
Ma S, Downard KM, Wong JWH (2015) FluClass: A Novel Algorithm and Approach to Score and Visualize the Phylogeny of the Influenza Virus using Mass Spectrometry, Anal. Chim. Acta, 895: 54-61. http://dx.doi.org/10.1016/j.aca.2015.09.004
Müller P, Downard KM (2015) Catechins Inhibit Influenza Neuraminidase and its Molecular Basis with Mass Spectrometry, J. Pharmaceut. Biomed. Anal. 111: 222-230. http://dx.doi.org/10.1016/j.jpba.2015.03.014
Downard KM (2015) in Encyclopedia of Mass Spectrometry, Vol 9B, eds. Nier KA, Yergey AL, Gale PJ, Elsevier: Netherlands, pp. 6-8.
Downard KM (2015) in Encyclopedia of Mass Spectrometry, Vol 9B, eds. Nier KA, Yergey AL, Gale PJ, Elsevier: Netherlands, pp. 25-26.
Akashi S, Maleknia SD, Saikusa K, Downard KM (2015) Stability of the βB2B3 Crystallin Heterodimer to Increased Oxidation by Radical Probe and Ion Mobility Mass Spectrometry, J. Struct. Biol., 189: 20-27. http://dx.doi.org/10.1016/j.jsb.2014.11.006
Swaminathan K, Müller P, Downard KM (2014) Substituent Effects on the Binding of Natural Product Anthocyanidin Inhibitors to Influenza Neuraminidase with Mass Spectrometry, Anal. Chim. Acta, 828: 61-69. http://dx.doi.org/10.1016/j.aca.2014.04.021
Maleknia SD, Downard KM (2014) Advances in Radical Probe Mass Spectrometry for Protein Footprinting in Chemical Biology Applications, Chem. Soc. Rev., 43, 3244 - 3258. http://dx.doi.org/10.1039/C3CS60432B
Fernandes ND, Downard KM (2014) Origins of the Reassortant H1N1 2009 Pandemic Influenza Virus by Proteotyping with Mass Spectrometry, J. Mass Spectrom., 49, 93-102. http://dx.doi.org/10.1002/jms.3310
Fernandes ND, Downard KM (2014) Incorporation of a Proteotyping Approach using Mass Spectrometry for the Surveillance of the Influenza Virus in Cell Culture, J. Clin. Microbio., 52, 725-735. http://dx.doi.org/10.1128/JCM.02315-13
Swaminathan K, Downard KM (2014) Evolution of Influenza Neuraminidase and the Detection of Antiviral Resistant Strains Using Mass Trees, Anal. Chem., 86: 629–637. http://dx.doi.org/10.1021/ac402892m
Downard KM (2013) Proteotyping for the Rapid Identification of Pandemic Influenza Virus and other Biopathogens, Chem. Soc. Rev., 42: 8584-8595. http://dx.doi.org/10.1039/C3CS60081E
Nasser Z, Swaminathan K, Müller P, Downard KM (2013) in-vitro Inhibition of the Influenza virus with the Anti-Viral Inhibitor Arbidol by a Proteomics based Approach with Mass Spectrometry, Antiviral Res., 100: 399-406. http://dx.doi.org/10.1016/j.antiviral.2013.08.021
Downard KM (2013) An Immunoproteomics Approach to Screen the Antigenicity of the Influenza Virus, in Methods in Molecular Biology: Immunoproteomics (Ed. S. Twine & K. Fulton), Vol. 1061, Ch. 8, pg 141-153. http://dx.doi.org/10.1007/978-1-62703-589-7_8
Swaminathan K, Dyason JC, Maggioni A, von Itzstein M, Downard KM (2013) Binding of a Natural Anthocyanin Inhibitor to Influenza Neuraminidase by Mass Spectrometry, Anal. Bio. Chem., 405: 6563-6572. http://dx.doi.org/10.1007/s00216-013-7068-x
Lun ATL, Swaminathan K, Wong JWH, Downard KM (2013) Mass Trees – A New Phylogenetic Approach and Algorithm to Chart Evolutionary History with Mass Spectrometry, Anal. Chem., 85: 5475-5482. http://dx.doi.org/10.1021/ac4005875
Nguyen AP, Downard KM (2013) Subtyping of Influenza Neuraminidase using Mass Spectrometry, Analyst, 138, 1787- 1793. http://dx.doi.org/10.1039/c3an00086a
Nguyen AP, Downard KM (2013) Proteotyping of the Parainfluenza Virus with High Resolution Mass Spectrometry, Anal. Chem., 85, 1097-1105. http://dx.doi.org/10.1021/ac302962u
Downard KM ed. (2007) Mass Spectrometry of Protein Interactions, John Wiley & Sons, New Jersey U.S.A. (ISBN 978-0-471-79373-1) http://au.wiley.com/WileyCDA/WileyTitle/productCd-0471793736.html
Downard KM (2004) Mass Spectrometry - A Foundation Course, Royal Society of Chemistry, Cambridge UK (ISBN 978-0-85404-609-6) http://www.rsc.org/shop/books/2004/9780854046096.asp