keVChem.com

Downard Laboratory WWW site

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 (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.

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INFLUENZA RESEARCH

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PROTEIN FOOTPRINTING

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 (FLU) is responsible for as many or more deaths in Australia today (over 4200 in 2017) 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.

We have developed bioinformatics approaches and algorithms (including FluTyper, FluShuffle and FluResort) and harnessed the power of high resolution mass spectrometry with high mass accuracy to type, subtype, determine the lineage and identify seasonal from reassorted pandemic strains through the detection of signature peptides by their mass alone. The approach has been applied to laboratory grown and clinical specimens and has advantages over conventional PCR based typing approaches including the speed of analysis and the directness of the proteotyping approach. More details can be found on this linked page (FLU)

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BIOINFORMATICS, PHYLONUMERICS

& COMPUTATIONAL BIOLOGY

A new structural biology approach employing a protein footprinting technology (also known by the acronym RP-MS) was first reported on in 1999. It challenged the traditional dogma that oxygen radicals only cause protein damage. When reacted on short millisecond timescales, proteins were found to undergo limited oxidation and that oxidation depends on the accessibility of reactive residues to the bulk solvent. Thus, it provided a means to study protein structures, folding events and interactions. The approach has also been developed in this laboratory employing a modified electrospray ionisation source 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.