Synthetic Biology 4.0 : highlights and reflections

Update: The videos of the talks from Synthetic Biology 4.0 are here !

Around three weeks ago I attended the Synthetic Biology 4.0 meeting in Hong Kong, hosted by the Hong Kong University of Science and Technology. I’ve taken a little time to allow all the new and exciting ideas to sink in. I really enjoyed the meeting, and while it was a little short it was an effective way to quickly sample the current developments in synthetic biology, as it stands.

Some highlights

Here are some summaries on a few highlight presentations. Due to parallel sessions, I couldn’t see every talk; luckily I’ll be able to catch up on those I missed once the videos appear online.

Clyde Hutchison (J. Craig Venter Institute), spoke about genome construction, specifically about rebuilding the minimal genome on Mycoplasma genitalium by synthesis of large fragments and subsequent stepwise assembly. This is probably not brand new work, but it was the first time I’d seen it presented. Turns out they could fully assemble the genome into a yeast vector from 25 large fragments using a ‘shot-gun’ approach with subsequent PCR screening to identify the correctly assembled construct.

Christopher Voight (UCSF) (and a poster presentation by Travis Bayer et al): Bio-MeX: A Novel Route from Biomass to Gasoline and Petrochemicals. Chris spoke about the work his lab is doing on producing methyl halides in E. coli and yeast. Methyl halides are a common feedstock in the petrochemical industry for producing many other organic chemicals, so a non-fossil fuel source will be useful in the future. I’ve always been a little skeptical about ocean metagenomic studies that sell themselves as the solution to the worlds energy problems, based on the notion that an amazing new enzyme will be discovered in marine bacteria. Well, this work coming out of Chris’ lab could prove me wrong … after screening 89 putative homologs of a methyl halide transferases from the various kingdoms of life (most annotated ‘methyl transferase’ in sequence database), the best one turned out the be from an “uncultured marine bacteria”, discovered by the Sargasso Sea Sequencing Project.

Eric Winfree (CalTech) spoke about his experiments with DNA tile-based crystals, as a potential model system for pre-biotic life. Crystal growth, breakage and regrowth models replication, the tiled ‘layers’ of different crystal variants form the genome. Don’t be mislead and assume that Eric is proposing that DNA of this nature was actually around in the primordial soup … it’s simply being used as a well understood system enabling specific molecular complementarity and template based replication (with errors); in theory this type of system could be built using any ‘crystal’ with similar properties.

Jay Keasling (UC Berkley, LBNL): Fuel and Drug Production: Jay gave some facts and figures about biofuel production from the metabolically engineered organisms which are ultimately being commercialised at Amyris. It was noted in the opening slides of several talks at this conference: Ethanol is not considered a very good gasoline replacement (lower energy density, too hydroscopic for existing pipeline infrastructure, high octane rating) when compared with n-butanol (higher energy density, less hydroscopic, controlled volitility, similar octane rating to gasoline). Watch the video for some well handled but potentially hairy questions about the source of feedstocks for biofuels production. On the science-side, Jay showed some interesting results from studies testing the effect of scaffolds for co-localising enzymes in a biosynthetic pathway of interest (as fusion proteins to PDZ, SH3 etc domains). After screening a library of scaffolds that would arrange different numbers of enzymes in different orders, one specific arrangment (“A-B-B-C-C”) worked better than other variations. No rational explaination, but interesting nonetheless.

Patrick Boyle et al from Pamela Silvers lab:  (poster presentation, The Synthetic Hydrogenosome: Subcellular Engineering for Biohydrogen production): showed how he was engineering yeast mitochondria for hydrogen production by introducing components of the pathway responsible from hydrogenosomes. This work caught my interest since for the past few years I’ve worked on aspects of protein import into mitochondria and related organelles (including a little bit of collaborative work on hydrogenosomes recently). Early versions of the engineered strain were producing small amounts of hydrogen compared with wildtype yeast … it will be interesting to see how far this can be optimized in the future (I don’t expect it to fuel a hydrogen economy anytime soon, but it’s early days).

Priscilla Purnick (Yale) spoke about her work helping engineer embryonic stem cells with genetic circuits to precisely control proliferation, differentiation and cell death, with the ultimate goal of treating Type I Diabetes with self-regulating beta-like insulin secreting cells. I couldn’t do justice to the technical details in a short summary here, needless to say it’s complex and impressive looking work. This was a spin off project from the Princeton iGEM team using many ‘off the shelf’ BioBricks(tm). While still in the early stages, the talk showed a nice mix of systems biology style modeling and hard experimental data.

I sat in on an open discussion session, entitled Legal Schemes and Rights. The key point that surprised me here was how little had actually been figured out surrounding the ‘intellectual property’ law of sharing, modifying, combining and (potentially) commercializing individual BioBrick[tm]-style parts, and devices built with such parts. I’d been under the delusion that the legal side was figured out early on, and that BioBrick parts were shared under some sort of MIT-like or BSD-like license. This is apparently not the case. Various possible legal frameworks were outlined, but I think the most insightful advice I heard was something to the effect of (paraphrased) .. “Don’t sit around treating this like an interesting academic problem .. pretty soon (~12 months ?) community norms for licensing parts will emerge by necessity and under the force of commercial interests, not by careful or considered design, and if you haven’t worked to establish things in the way that is best for proliferation of the technology and all stakeholders, it will be too late to change course. We have seen this has happen in other industries, it will happen here too”. Watch the videos once they appear if you want the correct quote, I can’t remember who said it now 🙂

I’ve half written a “part 2” to this post, outlining some ideas on the current state of Synthetic Biology as a field … but I’ll probably never publish it since it’s mostly just me organizing my slightly opinionated thoughts out loud. The summary is: there is currently a lot of excitement, potentially a little hype (see Gartner’s hype cycle, pick where you think Synthetic Biology currently sits on the curve). It will be interesting how this pans out, particularly if expectations have been unrealistically inflated. There has also been a bit of quibbling over the definition of Synthetic Biology; those engineers that have forged the field are probably pretty bored of the old ‘definition debate’ by now, but many biologists still don’t really know what Synthetic Biology is. Based on discussions I’ve had with colleagues about the conference content upon returning, the average molecular biologist doesn’t always see how Synthetic Biology is very different to what various bioscientists have been doing under the banner of Biotechnology for many years. My simplest explaination is that the underlying technologies are essentially the same, but the approach, the application of formal engineering principles and their use in a rational way to create useful ‘devices’, is different from past practices that have largely focused on discovering new knowledge about biological systems with many useful technologies arising in a more ‘undirected’ and opportunistic fashion. It’s great to be living in a time when the foundational knowledge in biology, built on decades (centuries?) of basic research, are slowly beginning to come to fruition in rationally designed technologies.

For another perspective, and little more on the buzz outside of the formal presentations, see s “Word on the Street @ SB 4.0” posts.

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