Snake venom glands grown in lab
For the first time, researchers were able to grow organoids from snake venom glands. The lab-grown 3-D structures can produce snake venom molecules. This is a major step in finding treatments to tackle snakebite, which causes over 100,000 deaths each year. Publication in top journal Cell.
A first question one might have is what organoids are. ‘Organoids are groups of cells grown in a Petri dish which are self-organising and have many of the same essential features as the original tissues,’ says Professor of Animal development Michael Richardson from the Institute of Biology Leiden (IBL). He and his team were involved in the study, which was led by Professor Hans Clevers at the Hubrecht Institute in collaboration with research partners in Amsterdam, Leiden, Liverpool, Maastricht and Utrecht. The researchers from Leiden contributed their expertise on snake embryology to this study. Organoids are derived from stem cells, and for the first time, scientists were able to establish organoids from reptiles.
To grow the organoids in the lab, the researchers used adult and embryonic stem cells from venom gland tissue from venomous snakes. With the use of a specific growth factor cocktail, the organoid cells kept on growing and dividing, even over long periods. The researchers studied the mRNA of the organoids and compared it with mRNA retrieved from snake venom gland cells. It revealed that the organoid cells have similar cell types as the snake tissues. The organoid cells were also able to produce venom molecules. Richardson was very pleased to see this result: ‘This was what we were hoping for. We want to be able to produce toxin molecules in the lab because it saves having to use animals for this purpose. The results also help us understand the different toxin-secreting cell types in the venom gland.’
Over 100,000 deaths
The organoids can be used as miniature venom factories in the lab. This enables researchers study snake venom and to develop new treatments to tackle snakebites. Venomous snakebites pose a threat to people all over the world, especially in developing countries, with over 100,000 deaths each year. The research team used highly venomous snake species to grow organoids from, including the Cape coral snake (Aspidelaps lubricus cowlesi).
Search for new antibiotics
The findings in this study are also promising for another project Richardson is involved in. He worked closely with Gilles van Wezel, Professor of Microbial Biotechnology at IBL, on the Top Sector-funded antibiotics research project Syngenopep. Richardson explains: ‘Animals produce a large variety of antimicrobial substances that may play an important role in controlling microbial infections. Now that we have these toxin factories established, we have more options to screen for antibiotic properties. Gilles van Wezel and our partners, including Harald Kerkkamp, have already patented one antimicrobial peptide from snake venom. So we are on a very promising path toward new effective drugs.’
Header image: Snake venom gland organoids (copyright: Princess Máxima Center for pediatric oncology, credits: Ravian van Ineveld)
From the Institute of Biology Leiden Professor Richardson worked together with analyst Merijn de Bakker and with PhD candidate Harald Kerkkamp on the organoid study. Kerkkamp works at both IBL and Naturalis Biodiversity Center, under shared supervision by Professor Richardson (IBL) and Freek Vonk (Naturalis).