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Venom-derived toxins as biochemical and pharmacological probes of pain pathway

  • Author(s): Bohlen, Christopher
  • Advisor(s): Julius, David
  • et al.
Abstract

Venoms often target vital processes to cause paralysis or death, but many types of venom also elicit notoriously intense pain. While these pain-producing effects can result as a byproduct of generalized tissue trauma, some venom-derived toxins target somatosensory nerve terminals in order to activate nociceptive (pain-sensing) neural pathways. In my thesis work, I have discovered two novel toxins that contribute to the exceptionally painful bites of the Earth Tiger tarantula (Ornithoctonus huwena) and the Texas coral snake (Micrurus tener tener) respectively. The Earth Tiger tarantula produces a novel tandem-repeated toxin that activates the capsaicin receptor, TRPV1, through a long-lasting, bivalent binding event. I have further employed this toxin to explore the structure-function relationships of its target, TRPV1. The Texas coral snake produces an unusual heteromeric toxin that activates members of the acid sensing ion channel family, and we have utilized it to explore the physiological contribution of the ASIC1 member of this family to pain sensation.

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