AVRU

Page Contents: Staff-Honorary Fellows-Collaborators | Funding/Awards | About | Clinical Research | Preclinical Research | Epidemiology | Education | Recent Publications

Staff and Graduate Researchers

Dr David Williams, BSc, GDipResMeth, PhD, Head
A/Prof Christine E. Wright, BSc Hons, PhD
Dr Kenneth D Winkel, MBBS, BMedSc, PhD, FACTM, Research fellow
Dr Ronelle Welton, BBioMedSc Hons, PhD, MPHTM, Research Fellow
Ms Dalia Ponce Garcia, BSc, MSc (UNAM, Mexico), PhD candidate

Principal Honorary Fellows

A/Prof James Tibballs, Royal Children's Hospital
Prof P. Gopalakrishnakone, National University of Singapore
Prof David Warrell, University of Oxford, UK

Honorary Fellows

Dr Simon Jensen, Nambour Hospital, Qld
Dr Bill Nimorakiotakis, Epworth and Western Hospitals
Dr Mark O'Shea, National Institute for Research into Aquatic Habitats, UK
Dr Wolfgang Wüster, University of Wales, Bangor, UK
Dr Nadine Levick, Miamonades Medical Center, NYC, USA
Dr Katia Barbaro, Institute Butantan, SP, Brazil
Dr Chris Barnes, Bundaberg Base Hospital

Collaborators

Prof Teatulohi Matainaho, PNG Chief Scientist
Prof José María Gutiérrez, Instituto Clodomiro Picado, Costa Rica
Prof Juan Calvete, Instituto de Biomedicina de Valencia, Spain
Mr Owen Paiva, Charles Campbell Toxinology Centre, University of PNG
Dr Robin Oge, Port Moresby General Hospital
Dr Lisa-Ann Gershwin
Dr Andrew Padula, Bairnsdale Animal Hospital
Mr Russell Hore, Quicksilver Connections, Port Douglas
A/Prof James Harrison, Flinders University
A/Prof Peter Fenner, James Cook University
Dr Angel Yanagihara, University of Hawaii
Dr Diane Brinkman, Australian Institute of Marine Science
Dr Jason Mulvenna, QIMR Berghofer Medical Research Institute
Sharyl Crossley, Senior Aquarist, Tennessee Aquarium

Website

www.avru.org/ (external website)

Funding/Awards

NH&MRC: A randomized, double-blinded controlled trial (RCT) of a new whole IgG, equine antivenom compared to the currently used F(ab')2 CSL taipan antivenom, for the treatment of Papuan taipan (Oxyuranus scutellatus) envenoming in Papua New Guinea [2012–2014]

Direct Australian Government NH&MRC: Research translation, engagement and injury surveillance [2013–2017]

The Struan Sutherland Trust

Miscellaneous small grants

About

Australia has an international reputation for being the epicentre of all things venomous, whether it happens to be venomous snakes and arthropods on land, bees and wasps in the air, or lethal jellyfish, stingrays, stonefish and octopi in our oceans. The Australian Venom Research Unit (AVRU) conducts research with two main focus areas. The first is to characterise venoms and toxins in order to better understand the mechanism of envenomation and apply this understanding to improve treatment outcomes. A novel activity identified through this work has the potential for use as an investigational tool to aid in medical research and may identify drug discovery leads. The second is the use of public health applications to translate research and knowledge within a public forum and in addition quantify the burden of injury through epidemiological works.

Clinical Research

A randomized, double-blinded controlled trial (RCT) of a new whole IgG, equine antivenom compared to the currently used F(ab')2 CSL taipan antivenom, for the treatment of Papuan taipan (Oxyuranus scutellatus) envenoming in Papua New Guinea

As part of its research activity, AVRU investigates the clinical presentation and management of venomous bites and stings. This work is focused on snakebite in Australia and the Asia-Pacific. It also aims to enhance the evidence base underlying contemporary recommendations in the prevention and treatment of venomous bite and sting injuries through direct clinical research. Our key project, funded by an NH&MRC Project grant, is a clinical trial of a new whole IgG equine Papuan taipan antivenom that is taking place at Port Moresby General Hospital in Papua New Guinea (PNG). This new antivenom has been developed in collaboration with colleagues from the Instituto Clodomiro Picado (Costa Rica) and the University of PNG, and is the first new antivenom to be used for snakebite in humans in Australasia in more than 50 years. The development of this product has been driven by a desire to develop a template for the production of high potency, safe, effective and affordable antivenoms for deployment in developing nations, delivering a GMP-compliant product that meets rigorous WHO Standards at a price that is sustainable in the long term. In preclinical studies our new antivenom was found to have equivalent overall potency against Papuan taipan (Oxyuranus scutellatus) venom to the current antivenom product, and improved neutralisation of procoagulant toxins that cause bleeding. The clinical trial is currently in progress. Our success with this project has led to the establishment of purpose-built clinical snakebite research laboratory (The Charles Campbell Toxinology Centre) at the University of Papua New Guinea. In addition to recruiting patients to our clinical trial, our Snakebite Clinic at the Port Moresby General Hospital is responsible for the management of approximately 250 snakebite cases that present to the Emergency Department each year, and we have extended service delivery beyond the hospital by establishing the only free MICA-level ambulance retrieval service in PNG which enables us to send a medical team out to health centres within 150 km of Port Moresby to stabilise, treat and safely transport critically ill snakebite patients back to hospital.

Preclinical Research

The cardiovascular pharmacology of snake venoms from Papua New Guinea and Australia

Papua New Guinean snakes produce a wide range of toxins that affect different organ systems. Apart from the dominant clinical effects caused by neurotoxins and procoagulants, the venoms of some PNG snakes are also known to affect the cardiovascular system. Patients bitten by Papuan taipans (Oxyuranus scutellatus) may experience syncope or loss of consciousness very soon after being bitten, and those who survive and present at hospital show cardiac rhythm disturbances that are thought to be due to direct cardiotoxic effects. In addition, other threatening cardiovascular events such as extreme lowering or raising of heart rate or blood pressure have been observed after envenoming by some PNG snake species, underlining the cardiotoxic potential of PNG snake venoms. We are especially interested in the cardiovascular pharmacology of Papuan taipan and PNG small-eyed snake (Micropechis ikaheka) venoms, as well as Australian brown snake (Pseudonaja spp.) and taipan (Oxyuranus spp.) venom. In close collaboration with the Cardiovascular Therapeutics Unit, our research aims to elucidate the mechanism of cardiotoxicity using isolated cardiovascular tissues in vitro and in integrated preparations in vivo. The effectiveness of antivenoms raised against these species in Australia and Costa Rica will be compared against cardiovascular responses to particular snake venoms. In doing so, we are seeking further insights into the action of these venoms, providing avenues for novel drug discovery, as well as improvements in the treatment of envenomation.

 

 

photo of Ronelle Welton in field laboratory

Dr Ronelle Welton: Public Health in Papua New Guinea Identifying venomous injury issues and risk, and the translation of research from the laboratory back to at-risk populations, are foci of public health at the AVRU.

photo of taipan patient

AVRU Papuan Taipan Antivenom Clinical Trial Principal Investigator, Dr Simon Jensen, monitoring a seriously ill patient who had been bitten by a Papuan taipan (Oxyuranus scutellatus) while walking home from his family's garden. INSET: The same patient preparing to go home from hospital 5 days later.

photo of ambulance

Just as our clinical research on snakebite is improving the hospital outcomes for envenomed patients, we have also committed to addressing other problems identified through the work of our team in PNG. One of the greatest challenges is access to expert medical care for rural victims. We are tackling this by providing PNG's only free Mobile Intensive Care Ambulance (MICA) service capable of retrieving critically ill patients who require airway intubation and ventilation in order to get them to hospital safely.
INSET: Emergency consultant Dr Desmond Aisi preparing a ventilated patient for transport to Port Moresby General Hospital from Agevairu Health Centre in rural Central Province.

photo of honours students in lab

University of PNG Honours students Ben Bande (left) and Julious Jacobs (right) preparing venom gland cDNA extracts for PCR in the collaboratively funded Charles Campbell Toxinology Laboratory (CCTC) at the University of PNG. Training future PNG scientists in basic laboratory techniques is an important way in which AVRU contributes to the community through its activities in Papua New Guinea. INSET: Papuan taipan (Oxyuranus scutellatus) hatching in CCTC's Serpentarium at UPNG; more than 50 snakes are kept there for research.

photo of students on field trip

Sharing Place, Learning Together
Sharing Place, Learning Together is an integrated, inquiry-based education program aimed at increasing multimodal scientific and literacy skills of remote Aboriginal students. It is a pilot program of the University of Melbourne at Maningrida College in Arnhem Land. In 2010, the AVRU was invited to contribute to Maningrida College's "Learning On Country" education program where students undertake fieldwork and integrated classroom activities with local rangers. Sharing Place, Learning Together supports and expands this program.

 

 

Isolation and characterization of major venom proteins from Scyphozoan jellyfish using proteomic, transcriptomic and pharmacological approaches


Jellyfish venoms are rich sources of bioactive compounds, however few toxins have been completely isolated and characterized. Basic research investigating the proteomes of jellyfish venoms may lead to the discovery of promising compounds for the development of therapeutic agents or probes to study physiological pathways. The Scyphozoans, or 'true' jellyfish, have been somewhat neglected for toxin studies, compared to the more dangerous box jellyfish. Proteomic, transcriptomic and pharmacological studies are essential to identify and isolate toxic proteins/peptides as well as to elucidate their structures, mechanisms of action and molecular targets. In collaboration with the Cardiovascular Therapeutics Unit, the Tennessee Aquarium, the Australian Institute of Marine Sciences in Townsville and the Queensland Institute of Medical Research in Brisbane, we are working with venoms from the Atlantic sea nettle, Chrysaora quinquecirrha, and the Pacific sea nettle, Chrysaora fuscescens, in order to explore the proteomics and transcriptomics of each venom and characterise the pharmacological activities of crude venoms and isolated toxins using in vitro and in vivo bioassays.

photo of person working in lab and of jellyfish (montage)

Chrysaora jellyfish Sea nettles are known to be severe stingers in numerous coasts around the world. Current research is focused on the isolation and molecular characterisation of venom toxins to understand the mechanisms of action underlying the toxic effects of their stings. Outcomes will also lead to a better understanding of venom complexity and improve current guidelines and treatments for jellyfish stings.

Epidemiology

The Australian Venomous Injury Project (AVIP), initiated in July 2014, has the goal to determine if there are significant and specific factors relevant to venomous injury by different types of organisms, environments, or specific individuals or groups of individuals that predispose them to poor outcomes. Australian national morbidity and mortality databases are being reviewed in order to note correlative associations to inform preclinical and public health research.

Education

Medical History

Medical History - Venom: Fear, Fascination and Discovery

From the first Dean of Medicine, the University of Melbourne has been part of the global debate on the nature of venom. Hence the AVRU builds on more than 150 years of venom research at the University. Material from diverse collections and archives of the University and associated institutions were combined to tell the story of the development and use of antivenom in Australia from colonial times until now.

For more information see the 'Visions' episode from July 2013 (http://feeds.unimelb.edu.au/melbourneunivisions.

 

photo of Dr Ken Winkel

Dr Ken Winkel is shown here discussing the 2013 Medical History Exhibition on this subject.

Sharing Place, Learning Together

The "Sharing Place, Learning Together" project is an inquiry-based education program aimed at increasing scientific and literacy skills of remote Aboriginal students. It is a pilot program of the University of Melbourne at Maningrida College in northeast Arnhem Land and expands upon the College's 'Learning on Country' activities that involved the discovery of several unknown venomous spider species. Students are supported to develop their own curriculum resources, building on a previous venom-focused curriculum resource project of the AVRU and Melbourne Graduate School of Education, a key University of Melbourne program partner.

RECENT PUBLICATIONS

  1. Paiva OK, Pla D, Wright CE, Beutler M, Sanz L, Gutiérrez JM, Williams DJ, Calvete JJ.
    Combined venom gland cDNA sequencing and venomics of the New Guinea small-eyed snake, Micropechis ikaheka. J Proteomics 2014; 110: 209-229.
  2. Pla D, Paiva OK, Sanz L, Wright CE, Beutler M, Calvete JJ, Williams DJ, Gutiérrez JM.
    Preclinical efficacy of Australian antivenoms against the venom of the small-eyed snake, Micropechis ikaheka, from Papua New Guinea: an antivenomics and neutralization study. J Proteomics 2014; 110: 198-208.
  3. Herrera M, Paiva OK, Pagotto AH, Segura A, Serrano SMT, Vargas M, Villalta M, Jensen SD, León G, Williams DJ, Gutiérrez JM.
    Antivenomic characterization of two antivenoms against the venom of the taipan, Oxyuranus scutellatus, from Papua New Guinea and Australia. Am. J. Trop. Med. Hyg 2014; 91: 887-894.
  4. Gutiérrez JM, Burnouf T, Harrison RA, Calvete JJ, Kuch U, Warrell DA, Williams DJ for the Global Snakebite Initiative.
    A multicomponent strategy to improve the availability of antivenom for treating snakebite envenoming. Bull World Health Organ 2014; 92: 532-536.
  5. Luna-Ramírez K, Bartok A, Restano-Cassulini R, Quintero-Hernández V, Coronas FIV, Christensen J, Wright CE, Panyi G, Possani LD.
    Structure, molecular modeling and function of a novel potassium channel blocker, urotoxin, isolated from the venom of the Australian scorpion Urodacus yaschenkoi. Mol Pharmacol 2014; 86: 28-41.
  6. Atakuziev BU, Wright CE, Graudins A, Nicholson GM & Winkel KD.
    Efficacy of Australian red-back spider (Latrodectus hasselti) antivenom in the treatment of clinical envenomation by the cupboard spider Steatoda capensis (Theridiidae). Toxicon 2014; 86: 68-78.
  7. Luna-Ramírez K, Sani MA, Silva-Sanchez J, Jiménez-Vargase JM, Reyna-Flores F, Winkel KD, Wright CE, Possani LD, Separovic F.
    Membrane interactions and biological activity of antimicrobial peptides from Australian scorpion. Biochim Biophys Acta 2014; 1838: 2140-2148.
  8. Luna-Ramírez K, Quintero-Hernández V, Vargas-Jaimes L, Batista CV, Winkel KD, Possani LD.
    Characterization of the venom from the Australian scorpion Urodacus yaschenkoi: molecular mass analysis of components, cDNA sequences and peptides with antimicrobial activity.
    Toxicon 2013; 63: 44-54.
  9. Gutiérrez JM, Warrell DA, Williams DJ, Jensen S, Brown N, Calvete JJ, Harrison RA.
    The need for full integration of snakebite envenoming within a global strategy to combat the neglected tropical diseases: the way forward. PLoS Negl Trop Dis 2013; 7: e2162.
  10. Warrell DA, Gutiérrez JM, Calvete JJ, Williams D.
    New approaches & technologies of venomics to meet the challenge of human envenoming by snakebites in India. Indian J Med Res 2013; 138: 38-59.
  11. Webb JC, Godinho SC, Woolley MF, Winkel KD.
    Sharing Place, Learning Together: the birthplace of new ways? Med J Aust 2013; 199: 69-71.
  12. Healy J, Winkel KD (Eds)
    Venom; Fear, Fascination and Discovery, Exhibition Catalogue, Medical History Museum. University of Melbourne, 2013, ISBN 978 0 7340 4834 9.
  13. Hughes RJA, Angus JA, Winkel KD, Wright CE.
    A pharmacological investigation of the venom extract of the Australian box jellyfish, Chironex fleckeri, in cardiac and vascular tissues.
    Toxicol Lett 2012; 209: 11-20.
  14. Herrera M, Fernández J, Vargas M, Villalta M, Segura A, León G, Angulo Y, Paiva O, Matainaho T, Jensen SD, Winkel KD, Calvete JJ, Williams DJ, Gutiérrez JM.
    Comparative proteomic analysis of the venom of the taipan snake, Oxyuranus scutellatus, from Papua New Guinea and Australia: Role of neurotoxic and procoagulant effects in venom toxicity.
    J Proteomics 2012; 75: 2128-2140.
  15. Vargas M, Segura A, Herrera M, Villalta M, Estrada R, Cerdas M, Paiva O, Matainaho T, Jensen SD, Winkel KD, León G, Gutiérrez JM, Williams DJ.
    Preclinical evaluation of caprylic acid-fractionated IgG antivenom for the treatment of Taipan (Oxyuranus scutellatus) envenoming in Papua New Guinea.
    PLoS Negl Trop Dis 2011; 5: e1144.
  16. Williams DJ, Brown N, Calvete J, Casewell N, Gutiérrez JM, Harrison R, Jensen SJ, Paiva O, Ratanabanangkoon K, Winkel KD, Wüster W, Warrell DA.
    Ending the drought: new strategies for improving the flow of affordable, effective antivenoms in Asia and Africa.
    J Proteomics 2011; 74: 1735-1767.
  17. Li R, Wright CE, Winkel KD, Gershwin LA, Angus JA.
    The pharmacology of Malo maxima jellyfish venom extract in isolated cardiovascular tissues: a probable cause of the Irukandji syndrome in Western Australia. Toxicol Lett 2011; 201: 221-229.
  18. Lippmann JM, Fenner PJ, Winkel K, Gershwin LA.
    Fatal and severe box jellyfish stings, including Irukandji stings, in Malaysia, 2000-2010.
    J Travel Med 2011; 18: 275-281.
  19. Gutiérrez JM, Williams DJ, Fan HW, Warrell DA.
    Snakebite envenoming from a global perspective: Towards an integrated approach.
    Toxicon 2010; 56: 1223-1235.
  20. Williams DJ, Gutiérrez JM, Harrison R, Warrell DA, White J, Winkel KD, Gopalakrishnakone P.
    An antidote for snake bite: The Global Snake Bite Initiative.
    Lancet 2010; 375: 89-91.