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Insight into snake venom evolution could aid drug discovery

18 September 2012

UK-led scientists have made a discovery about snake venom that could lead to the development of new drugs to treat a range of life-threatening conditions like cancer, diabetes and high blood pressure.

Most venom contains a huge variety of lethal molecules called toxins, which have evolved from harmless compounds that used to do different jobs elsewhere in the body. These toxins target normal biological processes in snakes' prey such as blood clotting or nerve cell signalling, stopping them from working properly.

Mohave Rattlesnake - an example of a venomous snake. Copyright Wolfgang Wüster.

Now researchers have discovered that the toxins that make snake and lizard venom deadly can evolve back into completely harmless molecules, raising the possibility that they could be developed into drugs.

NERC-funded researcher and lead author of the study, Dr Nicholas Casewell from Liverpool School of Tropical Medicine, explains, "Our results demonstrate that the evolution of venoms is a really complex process. The venom gland of snakes appears to be a melting pot for evolving new functions for molecules, some of which are retained in venom for killing prey, while others go on to serve new functions in other tissues in the body."

Scientists have long recognised that the way that toxins work makes them useful targets for drug discovery. But the fact that they're harmful poses a problem. This means that drug developers have had to modify toxins to retain their potency and make them safe for drug use.

But the researchers' discovery that there may be many harmless versions of these toxins throughout a snake's body opens the door to a whole new era of drug discovery.

Snake researchers were aware that venom toxins evolve from harmless molecules that do fairly mundane jobs elsewhere in the body. But until now they had assumed that this was a one-way process.

Casewell and colleagues from Bangor University and the Australian National University used recently published gene sequences from the Garter snake and the Burmese python in their study. They compared these sequences with those from venom glands in a wide range of snakes and lizards, constructing an evolutionary tree to work out the relationships between the various sequences.

Dr Wolfgang Wüster from Bangor University, a co-author of the study, says, "Many snake venom toxins target the same physiological pathways that doctors would like to target to treat a variety of medical conditions. Understanding how toxins can be tamed into harmless physiological proteins may aid development of cures from venom."

The researchers' findings are published in Nature Communications today.

Further information

NERC Press Office
Natural Environment Research Council
Polaris House, North Star Avenue
Swindon, SN2 1EU
Tel: 01793 411561
Mob: 07917 557215

Scientists' contact details:

Dr Nicholas Casewell (primary contact)
Liverpool School of Tropical Medicine
Mob: 07811 057341

Dr Wolfgang Wüster
Bangor University
Mob: 07525 340513
(contactable from 16-19 September 2012)

Notes

1. This press release is based on the paper 'Dynamic evolution of venom proteins in squamate reptiles', Nicholas R Casewell, Gavin A Huttley and Wolfgang Wüster, due to be published in Nature Communications on 18 September 2012.

2. NERC is the UK's main agency for funding and managing world-class research, training and knowledge exchange in the environmental sciences. It coordinates some of the world's most exciting research projects, tackling major issues such as climate change, food security, environmental influences on human health, the genetic make-up of life on earth, and much more. NERC receives around £300m a year from the government's science budget, which it uses to fund research and training in universities and its own research centres.

3. Bangor University has a long record of academic excellence. The university was ranked top for teaching excellence in Wales, and 15th in the UK in the Sunday Times University Guide 2012. The University currently has 11,000 students and offers 500 degree programmes, with particular strengths in the fields of environmental science (including ocean sciences), health (including psychology, neuroscience and sports science), humanities, physical sciences, business, law, social sciences and education. It is a research-led university, and the 2008 Research Assessment Exercise demonstrated that it had 'world-leading' research in every subject area assessed, and in Accounting & Finance was judged to have the highest-rated research in the UK.

4. The Molecular Ecology & Evolution of Reptiles Research Group at Bangor University's School of Biological Sciences is the largest herpetology group in the UK, and one of the world's focal groups studying reptile evolution. It is a highly productive laboratory, with publications in Science, Nature, and PNAS, as well as leading evolutionary journals.

Press release: 24/12

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