SynBio Newsreel, October

Synbio community news

  • So, SynBioBeta (San Francisco) happened. SynBioBeta summarized the achievements and announcements from the synbio industry, while Aaron Dy of PLOS SynBio wrote a typically excellent perspective piece of the broader issues and intellectual currents running through the synbio industry’s largest conference.
  • My favorite science writer, Ed Yong, wrote a piece on the freeze-dried sensing and production systems pioneered by Collins lab. And there’s even a quote from new Northwestern professor Danielle Tullman-Ercek in there!
  • The Department of Energy’s Bioenergy Technologies Office (BETO) announces a $35 million advanced biofoundry centered at Lawrence Livermore National Laboratory.
  • If Elon Musk wants to colonize Mars, he’s going to need biotechnology. The Motley Fool’s Maxx Chatsko explains why.
  • Tobi Ogunnaike at SingularityHub looks ahead to the questions and challenges that face the field of DNA data storage.
  • BBC Horizons devotes an entire show to synthetic biology. Craig Venter, Christina Smolke, Amyris and IndieBio all feature.

Synbio profiles

Industry news

  • Venture capital interest in synbio continues to rapidly grow. Last year, synthetic biology companies raised half a billion dollars, and it looks like that trend is going to continue. Zymergen, the west coast’s answer to Ginkgo Bioworks, raised a $130 million Series B round. (Zymergen also happens to run a really excellent Medium account that links to several in-depth posts about their data-driven approach and vision for synbio). IndieBio announced its 4th class, including companies tackling the antivenin shortage and the cost of high throughput biotech equipmentNew VC firm Fifty Years, founded to fund companies that will help the world meet the UN’s Sustainable Development Goals, is particularly interested in synthetic biology. And buried in this fascinating profile of Y Combinator head Sam Altman is a reference to his plans to build a synthetic biology unit within the research arm of YC.
  • Oxford Nanopore continues to be awesome. Their MinION sequencer is already cool (its current capabilities are summarized nicely here), but it looks like their whole platform will get even more exciting soon. In a technical update (full video here), they announce impressive upgrades in sequencing on the MinION, and a number of truly exciting future projects. Is a gigabase-per-second sequencer possible? Will GATTACA-like portable sequencers soon be everywhere? I wouldn’t bet against it in the next decade.
  • Jason Kelly, CEO of Ginkgo, argues that synbio companies need to both specialize more and collaborate more, rather than trying to do everything in-house. Also, Xconomy tours and profiles Ginkgo, highlighting their recent deals with Amyris and Genomatica.
  • Speaking of Amyris, they and Synthetic Genomics, two of the oldest synbio companies, are pivoting away from biofuels and towards biopharmaceuticals. It’s a smart move given the margins in pharma, but also a sobering acknowledgment that economically competitive and renewable biofuels are a long way off.
  • Egelie et al. comprehensively survey the CRISPR patent landscape, which is quickly starting to look very thicket-y.
  • Startup 20n writes a blog post about how deep learning algorithms can simplify and speed up high-throughput metabolomic analysis and facilitate strain engineering.

Books and Longreads

  • I read (actually, listened to) Siddartha Mukherjee’s The Gene: An Intimate History this month, and I cannot recommend it enough. Mukherjee takes the reader/listener all the way from ancient Greek theories of inheritance, though the discovery of evolution and the rise of eugenics, to the molecular biology and biotech revolutions, to the Human Genome Project and the sequencing revolution, and right up to the current state of the art in gene diagnosis and editing, all while centering the book around his own family’s struggles with mental illness. The best nonfiction book I’ve read since I Contain Multitudes.
  • Springer published a Synthetic DNA protocols book. Highlights include a 6 hour cloning protocol and instructions for de novo gene synthesis and error correction from oligonucleotide arrays. Worth checking out!

Biosecurity

  • In order to prevent secretive/unsafe research on CRISPR gene drives, Kevin Esvelt floats the idea of using his patents to force scientists to publish open plans and protocols for gene drive research. The article also includes a 20 minute talk from Esvelt that summarizes current projects to develop and deploy gene drives to treat diseases in the world.

Now, on to the research papers!

Biomolecule engineering

  • Giessen and Silver turn a phage capsid into a highly stable bacterial microcompartment which concentrates enzymes of interest, is stable for a week at room temperature and increases indigo synthesis in E. coli by 60%.
  • Hartig lab modifies Twister ribozymes into a relatively modular, programmable system for controlling gene expression, developing sensor/switches that activate or repress gene expression in the presence of small molecule inputs in both E. coli and yeast.

Genetic circuits

  • The repressilator gets a major upgrade: by deleting a protein degradation gene and adding binding sites for one of the repressors, Potvin-Trottier et al. make the original repressilator circuit oscillate robustly and synchronously over more than 60 generations.
  • The discovery of new and useful enzymes from genome databases remains one of synbio’s rate limiting challenges. Genee et al. have developed a modular, riboswitch-based system to select importers of specific molecules from a library of uncharacterized bacterial importers.

Cell-free synbio

  • Some familiar names here! Jessica Perez, Jessica Stark and Mike Jewett review the state of the art in cell-free protein synthesis.
  • Krinsky et al. report a method to generate crude cell-free lysate in less than an hour.

CRISPR/gene editing

The strains, they are a changin’

  • Bryn Adams argues in ACS Synthetic Biology that we need new platform organisms beyond the molecular biology models of yesteryear, like E. coli and S. cerevisiae. Adams’s most interesting argument (to me) is that extremophiles are better platforms because their growth conditions can be the only selection marker needed to prevent contamination.

Metabolic engineering

  • Synthesis from CO2 and sunlight (well, actually fluorescent lamps): Woo lab engineers cyanobacteria to produce amorphadiene, a precursor for the antimalarial drug artemisinin.
  • How do you grow giant batches of bioproductive microbes without antibiotics, and avoid culture contamination? Use an extremophile! Chen lab engineers halophilic, alkaliniphilic Halomonas bacterium to produce protein surfactant PhaP. It’s Bryn Adams’s perspective piece in action!
  • Professors from Waginengin University in the Netherlands review the progress and potential of microbial autotrophs to produce useful chemicals. Key point for me: plants are less energetically efficient than cyanobacteria/microalgae, and cyanobacteria/microalgae are less efficient than chemolithoautotrophs hooked up to solar panels and water splitting catalysts. However, energetic efficiency and productivity are very different things.
  • Borkowski et al. argue in a review that the metabolic load of genetic circuits on cells should be as important a design consideration as circuit performance.

Computational biology

  • Northwestern’s own Leonard lab improves quantitative biology by developing a modeling strategy for predicting how DNA replication and gene copy number affect expression from different genome loci under a variety of growth conditions in E. coli.
  • Do you ever find yourself torn between designing your genetic pathway by composition, or by optimization? Do you have no idea what ‘design by composition’ or ‘design by optimization’ are? Well, a new paper from Tanevski et al. could help solve both those problems. They report a way to combine libraries of standardized parts with mathematical models of the desired behavior of a genetic circuit, make a bunch of possible compositions of parts to satisfy the desired behavior, and rank/optimize those compositions.

Tissue engineering

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