We are literally surrounded by venomous animals, which make up about 15% of all animal species on the planet. Venoms are unique model systems for studying protein evolution because the ongoing battle between venomous animals and their prey and predators places a constant selection pressure on venom toxins. As a result, most venoms are complex chemical cocktails, and they have proven to be an extremely valuable source of pharmacological tools, eco-friendly bioinsecticides, and human therapeutics.
Venoms vary greatly in composition because the animals that produce them have evolved to target different prey or deter different predators (or competitors in the case of platypus venom). Yet we still know very little about the composition of many animal venoms. Prior to this century, venom research focused on animals that produce large amounts of venom (e.g., snakes and large spiders) because these were amenable to the low-sensitivity analytical tools available at the time. The introduction of high-sensitivity, high-resolution MS-based proteomics in the early 2000s completely transformed the study of venoms. Tandem MS, in combination with venom-gland transcriptomics, now allows the assembly of high fidelity venom proteomes from microgram amounts of venom and nanogram amounts of venom-gland mRNA. In recent years, these technical developments have enabled the first comprehensive overview of the venom proteome of a wide variety of small venomous invertebrates, including ants, assassin bugs, centipedes, parasitoid wasps, pseudoscorpions, and robber flies. MS-based methods have also been critical for cataloguing the extraordinary diversity of post-translational modifications used to augment venom toxins. Although still in its infancy, the recent introduction of MS imaging has unveiled enormous potential to shed light on the location and mechanism of toxin production, and the functional role of toxins.
I will show seminal examples of how MS-based proteomics has enabled new insights into venom composition, venom evolution, venom production, and toxin structure and function.