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Venoms and Toxins

Background

Australia is home to some of the most venomous creatures in the world. To date little, if any, work has been undertaken on many of these venoms. The focus of our group is on the pharmacological and biochemical examination of venoms from Australasian animals. We are interested in identifying the primary mode of action of these venoms and isolating and characterising components. We are also interested in examining whether the currently available antivenoms can be utilised for envenomation by other species (some closely related while others are not).  This research will help in the identification of new, or improved, treatment strategies, the identification of new highly potent research tools and the identification of lead compounds for pharmaceuticals.

Snake venoms

Death adders, black snakes and taipans

We are currently isolating and characterising a number of components from these venoms. We have access to a large range of venoms from these genus.

Colubrids

Serious envenomation by colubrids is rare. Neurotoxicity rarely features in clinical reports of colubrid envenomings but has been documented in vitro in a number of species. Only two colubrid species, Boiga irregularis (Colubrinae) and Malpolon monspessulanus (Psammophiinae), have been reported in the literature as causing clinically significant neurotoxicity, while there are less clear-cut reports for others, such as the colubrines Boiga blandingii, Coluber rhodorachis and Coluber viridiflavus and the xenodontine Hydrodynastes gigas. The activity of many other colubrid venoms remains to be elucidated. We are examining the venoms from a range of colubrids including those from the Colubrinae, Homalopsinae, Natricinae, Psammophiinae and Pseudoxyrhophiinae snake families. These results will greatly increase the pharmacological knowledge of colubrid venoms while lending some insight into potential clinical effects and the evolution of venom components.

Marine venoms

Jellyfish

Box jellyfish are responsible for significant morbidity and occasionally mortality in northern Australia. The class cubozoa (box jellyfish) is divided into two orders: Chirodropidae, which includes the Indo-Pacific box jellyfish (Chironex fleckeri), and Carybdea, typified by Carukia barnesi. The clinical effects of these jellyfish appear to be mainly cardiovascular and autonomic. However, the mechanism(s) of the effects are not understood. Severe Chironex fleckeri envenoming results in cardiovascular collapse in humans and recent work in our laboratory has suggested that this is principally a cardiac effect. In contrast, the Irukandji syndrome due to Carukia barnesi is characterised by generalised pain, hypertension, nausea, vomiting and anxiety that has been purported to result from a hypercatecholaminergic state.

Despite the regularity and severity of jellyfish envenomings our understanding of the action of jellyfish venoms and toxins remains in its infancy. Recent data from our laboratory suggests that Chironex fleckeri antivenom is not as effective as previously thought. Therefore, research needs to focus on characterising the effects of jellyfish venoms so that treatment strategies based on a clear understanding of the mechanism of action of these venoms can be developed. In addition, the effects of the venom appear to be novel and fractionation of the venom may lead to the discovery of novel toxins that affect the cardiovascular system. This work is currently funded by the NHMRC.

Spider venoms

We are examining the venoms from a range of Australian spiders including the Northern Mouse spider (Missulena pruinosa), Eastern mouse spider (Missulena bradleyi), white-tailed spider (Lampona sp.) and wolf spider (Lycosa sp. ).

Personnel

  • A/Professor Wayne Hodgson
  • Dr Geoff Isbister (Honorary Senior Lecturer)
  • Dr Volker Herzig (Postdoctoral Fellow)
  • Andrew Hart (PhD student)
  • Kelly Winter (PhD student)
  • Dr Eddie Rowan (University of Strathclyde, Glasgow, Scotland - External consultant)

Collaborators

  • A/Professor Graham Nicholson (University of Technology, Sydney)
  • Professor Ian Smith (Department of Biochemistry & Molecular Biology, Monash University)
  • Dr Pierre Escoubas (Nice, France)
  • Dr Jamie Seymour (James Cook University, Queensland)
  • Dr Bryan Grieg Fry (University of Melbourne)

Recent key publications

  1. Fry, B.G., Vidal, N., Norman, J.A., Vonk, F.J., Scheib, H., Ramjan, R., Kuruppu, S., Fung, K., Hedges, S.B., Richardson, M.K., Hodgson, W.C., Ignjatovic, V., Summerhayes, R. & Kochva, E. Early evolution of the venom system in lizards and snakes. Nature, 439, 584-588, 2006.
  2. Hart, A.J., Smith, A.I., Reeve, S. & Hodgson, W.C. Isolation and characterisation of acanmyotoxin-2 and acanmyotoxin-3, myotoxins from the venom of the death adder Acanthophis sp. Seram. Biochem. Pharmacol., 70, 1807-1813, 2005.
  3. Kuruppu, S., Reeve, S., Banerjee, Y., Kini, R.M., Smith, A.I. & Hodgson, W.C. Isolation and pharmacological characterisation of cannitoxin, a presynaptic neurotoxin from the venom of the Papuan taipan (Oxyuranus scutellatus canni). J. Pharmacol. Exp. Ther., 315, 1196-1202, 2005.
  4. Kuruppu, S., Reeve, S., Smith, A.I. & Hodgson, W.C. Isolation and pharmacological characterisation of papuantoxin-1, a postsynaptic neurotoxin from the venom of the Papuan black snake (Pseudechis papuanus). Biochem. Pharmacol., 70, 794-800, 2005.
  5. Wen, S., Wilson, D.T.R., Kuruppu, S., Korsinczky, M.L.J., Hedrick, J., Pang, L., Szeto, T., Hodgson, W.C., Alewood, P.F. & Nicholson, G.M. Discovery of an MIT-like atracotoxin family: spider venom peptides that share sequence homology but not pharmacological properties with AVIT family proteins. Peptides, 26, 2412-2426, 2005.
  6. Kuruppu, S., Isbister, G.K. & Hodgson, W.C. Phospholipase A2 dependent effects of the venom from the New Guinean small-eyed snake Micropechis ikaheka. Muscle and Nerve, 32, 81-87, 2005.
  7. Pung, Y.F., Wong, T-H.P., Kumar, P.P., Hodgson, W.C. & Kini, R.M. Ohanin, a novel protein from king cobra venom induces hypolocomotion and hyperalgesia in mice: its identification, isolation, expression and functional characterization. J. Biol. Chem., 280, 13137-13147, 2005.
  8. Ramasamy, S., Fry, B.G. & Hodgson, W.C. Neurotoxic effects of venoms from seven species of Australasian black snakes (Pseudechis): efficacy of black and tiger snake antivenoms. Clin. Exp. Pharmacol. Physiol., 32, 7-12, 2005.
  9. Kuruppu, S., Fry, B.G. & Hodgson, W.C. Presynaptic neuromuscular activity of venom from the Brown-Headed Snake (Furina tristis). Toxicon, 45, 383-388, 2005.
  10. Lumsden, N.G., Fry, B.G., Ventura, S., Kini, R.M. & Hodgson, W.C. Pharmacological characterisation of a neurotoxin from the venom of Boiga dendrophila (Mangrove catsnake). Toxicon, 45, 329-334, 2005.
  11. Ramasamy, S., Isbister, G.K., Seymour, J.E. & Hodgson, W.C. The in vivo cardiovascular effects of an Australasian box jellyfish (Chiropsalmus sp.) venom in rats. Toxicon, 45, 321-327, 2005.
  12. Fry, B.G., Wickramaratna, J.C., Lemme, S., Beuve, A., Garbers, D., Hodgson, W.C. & Alewood, P. Novel natriuretic peptides from the venom of the inland taipan (Oxyuranus microlepidotus): isolation, chemical and biological characterisation. Biochem. Biophys. Res. Commun., 327, 1011-1015, 2005.
  13. Lumsden, N.G., Ventura, S., Dauer, R. & Hodgson, W.C. A biochemical and pharmacological examination of Rhamphiophis oxyrhynchus (Rufous beaked snake)venom. Toxicon, 45, 219-231, 2005.
  14. Ramasamy, S., Isbister, G.K., Seymour, J.E. & Hodgson, W.C. Pharmacologically distinct cardiovascular effects of box jellyfish (Chironex fleckeri) venom and a tentacle-only extract in rats. Toxicol. Lett., 155, 219-226, 2005.
  15. Ramasamy, S., Isbister, G.K., Seymour, J.E. & Hodgson, W.C. The in vivo cardiovascular effects of the Irukandji jellyfish (Carukia barnesi) nematocyst venom and a tentacle extract in rats. Toxicol. Lett., 155, 135-141, 2005.
  16. Joseph, R., Pahari, S., Hodgson, W.C. & Kini, R.M. (Invited review) Hypotensive agents from snake venoms. Curr. Drug Targets Cardiovasc. Haematol. Disord., 4, 437-459, 2004.
  17. Lumsden, N.G., Fry, B.G., Ventura, S., Kini, R.M. & Hodgson, W.C. The in vitro and in vivo pharmacological activity of Boiga dendrophila (mangrove catsnake)venom. Autonom. Autacoid Pharmacol., 24, 107-113, 2004.
  18. Ramasamy, S., Isbister, G.K. & Hodgson, W.C. The efficacy of two antivenoms against the in vitro myotoxic effects of black snake (Pseudechis) venoms in the chick biventer cervicis nerve-muscle preparation. Toxicon, 44, 837-845, 2004.
  19. Chetty, N., Du, A., Hodgson, W.C., Winkel, K. & Fry, B.G. The in vitro neuromuscular activity of Indo-Pacific sea-snake venoms: efficacy of two commercially available antivenoms. Toxicon, 44, 193-200, 2004.
  20. Wickramaratna, J.C., Fry, B.G., Loiacono, R.E., Aguilar, M.I., Alewood, P.F. & Hodgson, W.C. Isolation and pharmacological characterisation of a neurotoxin from the venom of the Acanthophis sp. Seram death adder. Biochem. Pharmacol., 68, 383-394, 2004.
  21. Lumsden, N.G., Fry, B.G., Kini, R.M. & Hodgson, W.C. In vitro neuromuscular activity of ‘colubrid’ venoms: clinical and evolutionary implications Toxicon, 43, 819-827, 2004.
  22. Ramasamy, S., Isbister, G.K., Seymour, J.E. & Hodgson, W.C. The in vivo cardiovascular effects of box jellyfish Chironex fleckeri venom in rats: efficacy of pre-treatment with antivenom, verapamil and magnesium sulphate. Toxicon, 43, 685-690, 2004.