Guest post by Jenna Gallegos
Last month, the fourth Gordon Research Conference (GRC) on Synthetic Biology was held in Waterville Valley, NH. Past conferences predominantly featured genome engineering and genetic circuits. This year, the unifying focus was directed evolution, the technology that earned Francis Arnold the 2018 Nobel Prize in Chemistry. The organizers also introduced several novel subsections that are likely to become staples in future meetings in the field.
In its most basic form, directed evolution involves randomly mutating sequences or organisms and then selecting those that perform best through iterative rounds of evolution. At face value, this type of shotgun approach seems at odds with the more design-focused strategies typical of synthetic biology.
The speakers at the 2019 GRC demonstrated how directed evolution can be incorporated into design-build-test workflows. For instance, Philip Romero from the University of Washington described how datasets produced through directed evolution can be used to build models of protein evolution which can in turn identify the amino acid residues that are most likely to be productive targets of future rounds of directed evolution using artificial intelligence.
Synthetic biologists are also putting their own twist on directed evolution, by taking the experiments out of the context of living cells. Although cell-free systems didn’t occupy their own subsection as at some meetings, talks and posters at the 2019 GRC featured topics such as engineering enzymes in vitro and modeling protein evolution in silico. In one of the keynotes, James Lalonde, described how Codexis is using ex vivo enzyme cascades to develop calorie-free sweeteners.
In vivo directed evolution as a tool for enhancing microbes used in biomanufacturing also featured prominently. Industry leaders and academics talked about engineering microbes to produce materials that are currently sourced unsustainably, as well as using biomanufacturing to build completely novel molecules and polymers. In two particularly fascinating seminars, David Breslauer of Bolt Threads presented on their progress using yeast to produce spider silk proteins, and Ann Meyer discussed several intriguing uses for biofilms built from engineered bacteria and modified 3D printers.
Beyond directed evolution, several speakers at the conference introduced calls to action for the community by demonstrating the challenges involved with scaling up. Physically scaling up, as in using larger fermenters for biomanufacturing, will require an improved understanding of the balance between growth and gene expression. To this end, Jose Jimenez from the University of Surrey discussed how his lab is using synthetic biology to engineer controls on cellular resource allocation.
Scaling up experiments to generate and analyze more data will require new advances in automation. Several talks and posters described using automation to design experiments, robotics to perform them, and models for analyzing large data sets; for example, to explore epistatic interactions on a systems level.
Synthetic biologists will also need to overcome several technological roadblocks in order to scale up from single-celled systems and microorganisms to multicellular tissues and diverse microbial communities. In a talk about artificial tissues, Kelly Stevens from the University of Washington explained how synthetic biology might be used to regulate expression to accomplish arrays of differential gene patterning in complex organs like the liver. On the community level, Angad Mehta talked about his work engineering yeast/bacterial endosymbionts at The Scripps Institute.
In addition to scientific discussions, this year’s GRC on Synthetic Biology included an Asilomar-inspired section specifically devoted to biosafety and biocontainment. But each seminar therein still focused predominantly on developing new life forms, not containing them. That may be, because – as Steven Benner reminded us in an intriguing talk about non-canonical nucleotides – many engineered organisms are difficult to keep alive even in the lab, making biocontainment a moot point.
Nonetheless, the time to talk about such issues is now, not after novel engineered organisms have been deployed, so the organizers should be commended for their attention to biosafety. In future conferences, it would be great to see this area expanded to include biosecurity as well.
The organizer’s commitment to ensuring diverse representation should also be applauded. Although there were fewer women speakers than men, the conference included a special breakout session on how to increase diversity, and several coveted speaker slots were held for very junior faculty. The conference attendees were also highly international, although the strongest representations by far came from Europe and the west and east coasts of the United States.
The take-home message from the conference was that, although we are far from replicating the complexity that has evolved naturally, we’re making great strides in that direction by taking advantage of organism’s and molecule’s natural tendency to evolve.
It was hard not to appreciate nature’s superiority in this department in the beautiful New Hampshire valley where the conference was held. Friendships made during the group hike led to thrilling conversations at the evening poster sessions for senior and junior scientists alike. The poster sessions were jam-packed and lubricated by the unlimited bar pass which most attendees purchased. And in true New England fashion, the conference ended with the traditional GRC lobster dinner, complete with several hilarious references to the translucent crab picture shared by Hiroki Ueda in a talk about tissue clearing earlier in the week.
Jenna Gallegos is a postdoc in Jean Peccoud’s lab at Colorado State University. Jenna’s work in the Peccoud lab focuses on high-throughput yeast genetics and cyberbiosecurity. She is also the News Editor for the Oxford Journal Synthetic Biology and a regular contributor to SynBioBeta and the Alliance for Science.