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Each venom peptide is expressed by a single gene. So to fully understand how the genes involved in producing venoms got weaponized for that purpose over the course of evolution, researchers need a system for manipulating those building blocks. That’s where organoids come into play.

Organoids are small tissue cultures that recapitulate the function of an organ in a petri dish. Holford hoped to use this technique to create a stockpile of venom gland organoids in her lab, in order to genetically manipulate how the genes in the venom glands work.

But never before has a marine invertebrate organoid been made. Over the course of the summer at MBL, Holford and her team made headway in growing a small number of glands and keeping them for a short amount of time. While she continues to hone this technique, she decided to explore another route for studying venom: cephalopods.

Carrie Albertin, an MBL Hibbitt Fellow who studies cephalopod genomics, had indicated that squid ink sacs can continue functioning outside of the animal. This led Holford to think that MBL’s cultured cephalopods may be the model organisms venom researchers seek to unravel how venom genes evolved and are regulated to produce such exquisite toxins.

After her experience at MBL, Holford is excited to begin studying cephalopods as “a way to go beyond the chemical interactions of peptides and bioactive toxins, and use laboratory organisms to  study toxin gene expression and gene evolution.This approach can shed light on the molecular processes that drive venom’s phenotypic diversity.”

“Without guiding principles for how venoms and venom glands develop in vivo, we and other venom researchers  have just scratched the surface,” she says. “We need lab models that can be manipulated in a controlled environment to revolutionize how we study venoms and venom gland biology, so that we can radically transform how we generate, modify, and utilize venom arsenals. Deciphering how complex traits like venoms occur in nature is a wide-open question.”

^{Two species of venomous cone snail, Conus striatus and Conus bullatus. Credit Mande Holford, MBL Whitman Fellow}