51³Ô¹Ïapp

Biography

About Me

After my undergraduate studies in Biotechnology from King’s College London, I completed a PhD at University College, London in molecular microbiology and protein biochemistry. In 1996, I started a period of Postdoctoral research at Macquarie University, Sydney, as a recipient of a Royal Society Fellowship. Then in 1998, I joined the Virology Division, Prince of Wales Hospital as Hepatitis Group Leader until 2002. In January 2003, I was appointed as a Senior Lecturer at UNSW and established a molecular microbiology research group and laboratory within the School of Biotechnology and Biomolecular Sciences. Currently, I lead a highly successful research team attracting substantial peer-reviewed and industry funding, as well as Postgraduate and Honours students. The main research areas of the lab include molecular virology, viral discovery, tracking pandemic noroviruses, the development of antiviralsÌýand viral evolution. In addition to leading the research group, I am also the course Coordinator for the third year science course Viruses and Disease (MICR3061), I teach 1st and 2nd year medical students, and I also lecture on numerous 1st, 2nd and 3rd year courses here at UNSW.

Education

• B.Sc. Hons (King’s College, London), 1992
• PhD (University College, London), 1996
• Fellow of the Australian Microbiology Society (FASM), 2011

Professional experience

• 2013-current: Professor, School of Biotechnology and Biomolecular Sciences (BABS)
• 2008-2012: Associate Professor, School of BABS
• 2003-2007: Senior Lecturer, School of BABS, UNSW
• 2003-current: Honorary Consultant Virologist, Prince of Wales Hospital
• 1998-2002: Hepatitis Group Leader, Virology Division, Prince of Wales Hospital
• 1997-1998: NHMRC-funded Postdoctoral Researcher, Macquarie University
• 1996-1997: Royal Society Postdoctoral Research Fellow, Macquarie University

Ìý

Research Programs

Project 1:Ìý Norovirus and replication and epidemiology

Norovirus is a major cause of gastroenteritis outbreaks worldwide. We track and study the evolution of pandemic norovirus strains across the globe, which are responsible for around 670 million cases and around 200,000 deaths each year. Major pandemics of norovirus gastroenteritis occur around every three to five years, with six pandemics reported since 1996. These pandemics are often associated with novel noroviruses from a single genotype (GII.4), which escape herd immunity through both antigenic drift and recombination. Our group is part of international and national networks that trace and track pandemic noroviruses globally. We first identified and characterised two of the six pandemic viruses; Hunter 2004 and Sydney 2012, both responsible for pandemics of gastroenteritis. We have developed several norovirus molecular detection and bioinformatics tools over the last few years for molecular virology studies using both clinical and wastewater samples in Melbourne and Sydney. The aim of this project is to conduct a detailed molecular epidemiological and evolutionary analysis of Australian noroviruses. The project will determine if current outbreaks are associated with the emergence of novel virus variants or recombinant (hybrid) viruses.

Ìý

Project 2:Ìý Adenovirus molecular epidemiology

Human adenoviruses (HAdVs) have been known to infect the gastrointestinal tract in conjunction with the upper or lower respiratory tract and ophthalmologic tissue. These icosahedral, dsDNA viruses can also infect other tissues including neurological tissue. In this study we argue against the current dogma and hypothesise that adenoviral gastroenteritis is not limited to typically ‘enteric’ species F (types 40 and 41). We have recently identified HAdV-A, B, and C Types associated with clinical gastroenteritis. Interestingly, unlike HAdV-F, these Types are more commonly attributed to tropism in respiratory tissues. Therefore, our findings implicate these Types with undiagnosed acute gastroenteritis. Using clinical and wastewater samples we aim to build on this hypothesis using cutting edge DNA amplification methods coupled with 3^rd generation sequencing techniques and bioinformatics. We will be able to determine the prevalent HAdV species the Sydney and Melbourne populations covering around 3 million people. We also aim to find which unidentified types are associated with acute gastroenteritis in Sydney.

Ìý

Project 3:Ìý Discovering new viruses (2 Honours places available)

In 2002, a metagenomics approach – the non-targeted sequencing of all DNA in a sample – was first used to find novel DNA viruses in a marine environment. Late such techniques were also developed for RNA viruses. For the first time, all viruses in a sample could be identified by their sequence, without the need for extensive culturing or PCR/RT-PCR techniques [44]. Since then, the advent of next generation sequencing (NGS) technologies have greatly facilitated this metagenomic approach to viral discovery. In contrast to Sanger sequencing-based studies, NGS allows the sequencing of millions of base pairs from a sample in a single run, massively increasing the number of viral genomes that can be discovered. NGS has thus revolutionised the field of viral discovery. The increase in readily-available computational power also permits rapid processing of this data, which can be compared to sequence databases, with, for example, the Basic Local Alignment Search Tool (BLAST) to identify the sample’s taxonomic constituents which for us are RNA viruses. These new techniques have revealed many divergent viral lineages are emerging many of which could pose challenges to the human population. Less than 1% of the earth’s virosphere is estimated to be known suggesting there are millions of potential human pathogens we know nothing about.
ÌýÌýÌýÌýÌýÌý In this space we have developed numerous work-flows using Katana (UNSW super computer) for viral discovery by accessing available public databases. We have targeted numerous animals for viral discovery including; bats, Australian reptiles and amphibians, over a dozen marsupials, monetremes and ancient fish. So far, we have discovered over 100 new viruses, for which we have many full-length viral genomes.ÌýIn a second more directed approach we have numerous viral discovery programs aimed at; the cane toad, paralysis tick, Tasmanian Devil and Australian fish. In these four metatranscriptomic projects we collect and sequence the entire RNA, usually from the liver, once ribosomal RNA has been removed. Our novel BINF work-flow, run from Katana, is then used to pull out viral sequences. Because we have the original samples containing the novel viruses, this hugely increases our chances of retrieving the entire source virus using one of two techniques. We can i) propagate the virus directly in cell culture systems using the infected tissue, or, ii) determine the full-length genome of the virus from infected tissue using RT-PCR methods and then resurrect the virus using reverse genetics. Using these methods, we have discovered 12 novel cane toad viruses, several of which are excellent bio-control candidates. This project involves a combination of wet lab work involving nucleic acid and virus extraction from animal tissues, and PCR amplification methods to find viruses.

Project 4:Ìý Paeleovirology: Finding ancient viruses in animal genomes using bioinformaticsÌý

The study of ancient viruses is termed paleovirology. The aim of this project is to find ancient viruses, or ‘fossil remnants of viruses’. The genomes of animals and insects contain traces of past viral infections through the integration of viral genetic material into the host germline, termed endogenous viral elements (EVEs). These viral fossils can be used to find viruses that existed thousands of years ago. Around 5% of the human genome is comprised of EVEs, of which the vast majority are retroviruses that naturally insert their genomes into the host genome as part of their life cycle. For other viruses, germ line integration is rare, but has been documented in many organisms. Using bioinformatics, our lab discovers EVEs in diverse groups of animals. Using genomes from mosquitoes, flies, and ticks, marsupials, including the koala and the Tasmanian Devil, we have identified hundreds of new EVEs. In addition, we have identified unique patterns that link to small RNA innate immune pathways in both the blacklegged tick Ixodes scapularis and in the Koala. We aim to find more viral fossils in the genomes of other animals, including monetremes which are ecologically threatened, and determine if they are used as a viral defence.

Project 5:Ìý Antiviral Research: Development of small compound antivirals

The group is also actively involved in the development of antiviral compounds, the repurposing current ones for new viruses. There is an active hunt for new, effective antivirals to treat and prevent viral infections, and drugs which target multiple viruses could be invaluable as a first line of defence. Our research focuses on the development of broad-spectrum, small compound antivirals, to combat positive sense RNA viruses such as; the pandemic coronavirus (SARS-CoV-2), viruses in the Caliciviridae (norovirus, feline calicivirus, RHDV), Flaviviridae (hepatitis C virus, Zika virus, dengue virus) and Hepeviridae (hepatitis E virus). Our main target is the viral RNA-dependent RNA polymerase (RdRp) because of its key role in viral replication. We have produced recombinant RdRps from many viruses, using Escherichia coli expression systems and used these to identify novel RdRp inhibitors. Promising inhibitors are taken forward to cell culture systems where we use live viruses and replicons to test their suitability as broad-spectrum drugs. In silico modelling is also performed on selected compounds to predict possible binding interations. The aim of the project is to conduct screening campaigns against the viral RdRps and replicons to identify lead compounds for antiviral therapies, and in particular against SARS-CoV-2.

Ìý

Teaching and Outreach

Courses I contribute to teaching

• MICR2011 - Microbiology 1 (2nd year) (Course Co-convenor)
• MICR3061 – Viruses and Disease (3rd year) (Course Convenor)
• BABS3200 -Synthetic Biology (3rd year)
• 1st and 2nd year Medicine

Professional affiliations and service positions

External - Societies

• Australian Centre for HIV and Hepatitis Virology (ACH2). Executive Committee member (2011-present)
• Australasian Virology Society, Committee Member (2009-2017)
• Fellow of the Australian Society of Microbiology (FASM) (2011-present)Ìý
• Member of the America Society for Microbiology (2004-present)
• Member of the Society for General Microbiology (1994-present)
• Australian Centre for Hepatitis Virology (ACHV) (President 2011-2013)
• Australian Centre for Hepatitis Virology, (Vice President 2006-2011)
• Australian Centre for Hepatitis Virology, (Treasurer 2002-2006)Ìý
• Australian Society of Microbiology, Division 2 Chair (2008-2010)
• Australian Society of Microbiology, Member of the National Scientific Advisory Committee 2008-2010
• ICTV Caliciviridae Study Group

Internal - UNSW

• UNSW Institutional Bio-Safety committee member (2003-2017)
• Postgraduate Coordinator School of BABS (2007- 2011)
• Honours Coordinator, School of BABS (2007-2010)
• UNSW Faculty of Engineering, External Promotion Committee Member (Associate Professor) (2008-2009)
• Committee Member, Human Research Ethics Advisory Panel D: Biomedical (2006-07)

Awards and Achievements

• 2015: Titan of Teaching Award, School of BABS, UNSW
• 1996: Royal Society (UK) Postdoctoral FellowshipÌý
• 1992-1996: Medical Research Council (MRC) PhD Scholarship