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Our new paper exploring the molecular nature of venom of limacodid caterpillar venoms featured on the cover of @PNASNews. This is one of the main things I've been working on in @VenomsLab the last few years and very happy to share it with you ... a thread https://www.pnas.org/content/118/18/e2023815118
these caterpillars are super cool and have eversible defensive spines that are tucked away at rest. You can see them in this video (also features me singing, sorry)
I got interested in these guys collecting assassin bugs with the Entomological Society of Queensland. Legendary entomologist Geoff Monteith recommended them as 'really bad—don't touch' and so I sat up and took notice. What could proteotranscriptomics tell us about their venom?
We did a review on insect venoms around this time, I was thinking about the insecticidal venom toxins of assassin bugs (Hemiptera: Reduviidae) and robber flies (Diptera: Asilidae) https://pubmed.ncbi.nlm.nih.gov/30267720/
and I wondered, do they have larger (protein rather than peptide) toxins because they are adapted from salivary secretions that were enzymatic?
if so, would venoms of these caterpillars that are not derived from salivary systems and instead parts of the cuticle be more peptidic, more similar to those of spiders and scorpions?
And to our suprise they were. You can collect limacodid venoms by touching some parafilm to their spines. You get hundreds of droplets of very tiny (nL?) venom, but very concentrated
We looked at the venom apparatus with old friend and total legend Dave Merritt, he found that each spine has a giant secretory cell at the base responsible for filling the spine lumen with venom
And so we did proteotranscriptomics, with help of the IMB sequencing facility, IMB proteomics facility, Trinity (love u), plus some software from @Venom__Doc
The results was astounding. This pain-causing venom was all basically peptides. HPLC of 0.5 mg venom (collected from hundreds of caterpillars, including in my garage, including during the 2019 nye countdown) showed us which peptides were the most abundant
There were three families of peptide that stood out to us: the first and most abundant in the venom is derived from the insect neuropeptide called adipokinetic hormone/corazonin-related peptide (ACP)
Knowing nothing about ACP, I emailed @JPPaluzzi who de-orphanised this neuropeptide and found its receptor in the first place. We sent him synthetic versions of the ACP-like toxins made Christina Schroeder
@JPPaluzzi showed they could activate a mosquito version of the channel with similar potency (sub-nanomolar) as the endogenous ligand. A weird thing about this study is that we still don't know why or how this translates to a fitness advantage to the caterpillar
when I say channel I of course mean receptor, the ACP receptor is a G-protein-coupled receptor
The second family we noticed are similar to cecropins, which are innate immunity peptides from non-venomous lepidopterans
these are cationic and look a lot like the venom peptides of ants, bees, and wasps! the aculeatoxins
We teamed up with @StingScience and @SensoryNeuroph1 who tested these peptides on mammalian peripheral sensory neurons (in particular, dorsal root ganglion cells responsible for relaying pain sensations) to find these cecropin-like peptides are responsible for the dominant effect
They are similar to toxins such as the bee venom peptide melittin and we think they work in the same way
The third family of venom toxins are likely inhibitor-cystine-knots (ICKs). This is a family of peptides that is amazingly well-represented in venom: they are the main peptides in spider venom and turn up in venoms of insects, cone snails, numerous other groups
Since the cecropin family have been found to have antiparasitic and antimicrobial effects we of course tested if the D. vulnerans venom peptides did
Luckily we had @SamNScience completing her PhD in the lab testing things for their ability to inhibit the larval development of an important sheep parasite, Haemonchus contortus
Surprisingly, what she found is that while the cecropin-like peptides kill the parasite with moderate (and expected) efficacies, one of the ICKs kills them with a much lower IC50, getting closer to the clinical antihelmintics.
We still have no idea why this is the case. @DesehGoud is our new PhD student making more peptides we discovered from the venom of this caterpillar and testing what they might do
We hope to learn more about venom toxin evolution and toxin structure/function relationships from these new studies! Stay tuned :)
