Norovirus, Hepatitis viruses, Viral evolution, Antiviral agents, Viral Transmission, Outbreaks, cane toad viruses.
Field of Research (FoR)
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...view more
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, the development of antivirals, tracking pandemic noroviruses and 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), and I lecture on numerous 1st, 2nd and 3rd year courses here at UNSW.
- B.Sc. Hons (King’s College, London) 1992
- PhD (University College, London) 1996
- 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
My Research Goals
Norovirus (NoV) is now recognised as the leading cause of acute gastroenteritis (AGE) accounting for approximately one fifth of all cases globally. NoV causes illness in around 684 million people every year, resulting in an estimated 218,000 deaths, mainly affecting children within developing countries. Aside from the significant mortality, the global societal costs caused by NoV exceed US $60 billion each year, as a result of health expenditure, morbidity and financial burdens caused by business closures, time off work and hospitalisations.
NoV transmission occurs primarily from person-to-person, however, transmission through contaminated food and water makes this virus a significant viral pathogen in terms of food and water outbreaks of gastroenteritis. Pandemics of acute gastroenteritis are associated with a genetic lineage of noroviruses called GII.4. Peter’s research over the last 18 years has examined evolutionary processes that have led to the emergence of pandemic NoVs.
Progress made so far in the molecular biology of NoV by White’s group has revealed the presence of a particularly important genotype of the virus, known as NoV Genogroup II, genotype 4 (GII.4; over 30 other genotypes of NoV exist), as the cause of global pandemics of gastroenteritis, accounting for more than 70% of all NoV infections. Since the first characterised global pandemic of acute gastroenteritis in the mid-1990s, Peter White's group has been instrumental in identifying and tracing the cause - pandemic GII.4 NoVs. Seminal work by White’s group has shown that the emergence of pandemic GII.4 NoVs is driven by two factors; i) the generation of point mutations in antigenic regions of the viral capsid, in an analogous manner to influenza, and ii) through recombination between two NoVs during a co-infection. Current research from the group on both human and mouse NoV involves development of antiviral agents and research into the host innate immune response, molecular epidemiology, pathogenesis and replication.
Peter's group has a strong collaboration with the New South Wales Ministry of Health, which monitors outbreaks of gastroenteritis for the State, as well as OzFoodNet and the NSW Public Health Unit. In 2007 Peter established the Australian and New Zealand Norovirus Surveillance Network, a network of large testing laboratories in major cities around Australia and New Zealand. The Network collectively monitors the emergence of new epidemic and pandemic viruses linked to outbreaks of NoV associated gastroenteritis. This network directly links in with two other networks, the Food-borne Viruses in Europe (FBVE) network and CaliciNet run by the U.S. Centres for Disease Control, to form the global Norovirus surveillance network, termed NoroNet. Collaborative work by the group was published in the Journal of Infectious Disease in 2009.
Our research focusses on the development of small compound antivirals, including non-nucleoside polymerase inhibitors, TL7 agonists and nucleoside analogues for the treatment of positive sense RNA viruses, including norovirus, hepatitis C virus (HCV), Zika virus, dengue virus, and other caliciviruses such as feline calicivirus and rabbit haemorrhagic disease virus. These positive sense RNA genomes replicate in the cytoplasm of the infected cell via minus-strand RNA intermediates. In the field of virology, there is an extremely active hunt for new antiviral agents to treat and prevent viral infections. One target for drug development is the viral RNA dependent RNA polymerase (RdRp) because of its key role in replication. Using our established methodology we have produced highly purified, soluble and active recombinant RdRps from a range of viruses, using Escherichia coli expression systems.
High throughput screening (HTS) is a standard platform used to identify lead chemical compounds for drug development. The aim of the antiviral program is to conduct high throughput screening (HTS) campaigns against the viral RNA polymerases to identify and characterise lead compounds and derivatives for potential antiviral therapy.
Hepatitis C Virus Research:
Infection with HCV contributes one of the most important health care burdens both in Australia and worldwide with more than 135 million people infected. The majority of infected individuals develop persistent infection (70%) and an associated risk of progressive fibrosis, cirrhosis, liver failure and hepatocellular carcinoma. In the field of HCV, Peter has contributed several landmark publications in relation to replication, molecular tools, HCV epidemiology, reinfection and antiviral agents. Using modern molecular biology techniques, next generation sequencing and bioinformatics, the group studies the replication and evolution of HCV within infected individuals.
Older therapies for HCV only worked in around 50-80% of infected patients and had adverse side effects, however because of intense research there is now a range of new antivirals that can now cure 95% of infected patients in 8-12 weeks. Most of these new drugs were made against genotype 1 HCV, whilst nearly half the Australian HCV infected population have a genotype 3 infection. The aim of this study is therefore to determine which genotype 1 antivirals work on genotype 3 HCV.
The study of ancient viruses has been termed paleovirology. The aim of this program is to resurrect and study ancient viruses, or “zombie viruses” that could be used as biocontrol agents for the control of insects that carry human pathogens such as dengue virus and West Nile virus.
The genomes of animals and insects contain traces of past viral infections through the integration of viral genetic material into the host genome, termed endogenous viral elements (EVEs). These viral fossils can be used to look at viruses that once existed thousands of years ago. Around 1% 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 extremely rare, but has been documented in many organisms. The most surprising viral fossils originate from RNA viruses.
The genome of the Aedes mosquito contains numerous sequences exhibiting similarity to viruses of the Flaviviridae family which comprise RNA viruses, as well as other viral families. Using the Aedes aegyptii genome we have identified 220 EVE fragments. Some we have pieced back together to create partial genomes of extinct viruses. The aim of this project is to determine if we can find ancient viruses within the DNA of other hosts, including the cane toad, which we are currently sequencing.
Contact Peter about research supervision opportunities: firstname.lastname@example.org
In the School of BABS we teach undergraduates, mentor postgraduate research students and conduct research in the disciplines of biotechnology, biochemistry, genetics, molecular biology, microbiology, environmental microbiology, medical microbiology and immunology. We empower our students, giving them the tools and experience to embark on a career that is richer, more fulfilling and constantly fascinating.
TEACHING & OUTREACH
Courses I contribute to teaching
BABS1202 - Applied Biomolecular Sciences (1st year)
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)
- Chair, Australia and New Zealand Norovirus Surveillance Network (2007-present)
- Fellow of the Australian Society of Microbiology (FASM) (2012-present)
- 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)
- 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 & ACHIEVEMENTS
- 2015: Titan of Teaching Award, School of BABS, UNSW
- 1996: Royal Society (UK) Postdoctoral Fellowship
- 1992-1996: Medical Research Council (MRC) PhD Scholarship
My Research Supervision
Areas of supervision
The Molecular Microbiology Laboratory lab is part of the School of Biotechnology and Biomolecular Sciences (BABS) and located in state-of-the-art facilities. Research in this multi-disciplined group encompasses molecular virology, antiviral drug discovery, viral evolution, viral biocontrol and paleovirology.
Project 1: Norovirus replication and epidemiology
Norovirus is the major cause of gastroenteritis outbreaks worldwide and is responsible for around 219,000 deaths each year. Major pandemics of norovirus gastroenteritis occur around every three years, with six pandemics since 1996. These pandemics are associated with novel noroviruses from a single genotype (GII.4), which escape herd immunity through both antigenic drift and shift. 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 global epidemics of gastroenteritis. We have developed a number of norovirus molecular detection and bioinformatics tools over the last few years for molecular virology studies. The aim of this project is to conduct a detailed molecular epidemiological and evolutionary analysis of Australian noroviruses, using both clinical samples and wastewater. The project will determine if current outbreaks are associated with the emergence of novel virus variants or recombinant (hybrid) viruses.
Project 2: Antiviral Research: Development of small compound antivirals
Traditionally, antiviral drugs have been ‘one drug, one bug’, meaning a new drug is required to treat every virus. 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 in the Caliciviridae (norovirus, feline calicivirus), 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 purified, soluble and active 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 where we use live viruses and replicons to test their suitability as broad-spectrum drugs. In silico modelling is also performed on promising compounds to predict possible binding interations. The aim of the antiviral project is to conduct screening campaigns against the viral RdRps to identify lead compounds for potential antiviral therapies.
Project 3: Discovering new cane toad viruses
In 1935, 101 Hawaiian cane toads were introduced into Queensland to control the cane beetle. Now, over 2 billion feral toads ravage 1.2 million km2 of northern Australia and threaten native species. One way to eliminate the cane toad is to find new, deadly, toad-specific viruses. Previous cane toad viruses were not suitable for biocontrol as they could affect native amphibians. The aim of this project is to increase our understanding of the cane toad and to find new viruses that can infect it. Our lab is collaborating with several institutions and we have already sequenced the entire 2 Gb cane toad genome for the first time. We are performing RNA-seq and PCR-based techniques on toad tissues sourced from diverse locations to find viruses that are infecting toads in nature. This project involves a combination of wet lab work involving nucleic acid and virus extraction from toad tissues, and PCR amplification methods to find viruses. This project also involves bioinformatic analysis of toad RNA-seq data and genomic data to find virus-like sequences.
Project 4: Paleovirology: Finding ancient viruses using bioinformatics
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 genome, 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 aims to find EVEs in diverse groups of animals. Using genomes from mosquitoes, flies, and ticks, we have identified hundreds of EVEs, and identified unique patterns and a link to innate immune pathways in the blacklegged tick Ixodes scapularis. We aim to find more viral fossils in the genomes of other animals, including marsupials, which are ecologically threatened.
Daniel Enosi Tuipulotu