Cultivarium

Nili Ostrov explains why we need more research on fungi and archaea – microbes which are relevant to human health, climate change and biotechnology. She’s the Co-founder and Chief Scientific Officer at Cultivarium, a non-profit research organisation based in the US. 🎥 Watch to find out about Cultivarium’s mission, supported by us, to develop advanced tools and technologies for life scientists to research these understudied microbes.

There are many fundamental bottlenecks that slow biology research down. Many of them are so basic that we rarely talk about them. One example is DNA delivery. Even if we can build a gene circuit, for example, we often can't get it into MOST organisms! For a recent preprint, Cultivarium (a FRO I've written about previously) built a custom electroporation robot that can explore many parameters to figure out which settings are best suited for transforming various types of cells. Electroporation is a technique wherein cells are literally shocked with electricity. This pulse of electricity punches holes in the cell membrane, thus allowing nearby DNA to float inside. One major benefit of electroporation is that it can be used on LOTS of different types of organisms, from bacteria to archaea and eukaryotes. The robot that Cultivarium made can test wash buffers, plasmids, organisms, voltages, and much more to find settings that actually work for a given new, non-model microbe. And using this custom device, they "report the first electroporation protocols...for eight non-model bacteria." Here are some things I learned that were surprising: > "The wash buffer used to prepare cells for electroporation had a significant effect on [transformation efficiency.]" Sometimes, remarkably so; "for each strain, one buffer showed at least 100-fold higher [transformation efficiencies] over other tested buffers." > The voltage applied to the cells is also super important. "Voltages greater than 1 kV had a variable effect, resulting in up to 1000-fold improvement in some species." > After finding settings that are *good enough* to transform a particular microbe, these researchers integrated an active learning pipeline to "iteratively improve...conditions to drive toward optimal parameters..." Using their robot, they tested 538 conditions over three cycles of experiments to improve the transformation protocol for a non-model microbe, called Cupriavidus necator. They were very quickly able to increase the transformation efficiency by 8.6-fold, just by tweaking wash buffers and voltages and other parameters! Anyway, I love these efforts to improve super fundamental aspects of biology research. They are highly underrated, and hopefully we'll soon see similar efforts for: - Making proteins much cheaper to produce in small volumes. - Cloning times - Predictive models for whether or not a given protein will be expressed in a given organism. (In the image below, you can see how different settings massively impact transformation efficiencies. There is also a plate layout at the bottom, showing how multiple celltypes were electroporated at various voltages and in different buffers.) Paper: https://lnkd.in/eWjh3jaT