SynBio Newsreel, July 2017

A day may come when I break these into several smaller posts. But it is not this day!

Biohacking is coming to Chicago!

  • Excited to announce the launch of ChiTownBio, a community biohacking/DIYbio organization. Our mission is to put the knowledge, skills, and tools of biotechnology into the hands of all Chicagoans who want to explore the living world and use it to benefit our community. Our kickoff event will be hosted at the Empirical Brewery on Wednesday August 9th at 7 pm. We will, among other things, make a DNAquiri, a cocktail that extracts and makes visible the DNA in strawberries.

Podcasts

  • The GeneMods podcast has new episodes! This month, we had a fascinating conversation with professor Julius Lucks about engineering RNA, and learned about lots of new synbio developments in the news quiz. We also recorded an extra episode about synthetic biology in science fiction.
  • GeneMods isn’t the only group talking about synbio on SoundCloud! I’ve reposted a bunch of synbio-related podcast episodes onto the GeneMods channel. Two of my favorites: an interview with NASA astrobiologist/bioengineer/badass Lynn Rothschild, and a conversation with CoderDojo founder and SOSV partner Bill Liao about a tech investor’s perspective on biohacking.

Videos

Books

  • Synthetic: How Life Got Made, by Sophia Roosth, is a first-person account of the birth of synthetic biology, as well as an anthropological analysis and critique of the field. The chapter on biohacking and DIYbio is particularly good. Great read.
  • Last month, before I had the chance to read it, I recommended A Crack in Creation, by Jennifer Doudna and her former student Samuel Sternberg. Now I’ve read it, and I recommend it even more. The context it provides on the history of genetic modification, gene therapy, and the discovery of CRISPR is very useful, but my favorite parts are the last few chapters, where Doudna talks about the future, and how her own views have evolved on germline gene editing.

Blogs and Community News

  • Favorite new magazine: Neo.life. A Medium-based publication started by Jane Metcalfe (one of the founders of Wired!), it focuses on engineering biology, mainly from a health and human augmentation perspective. Their book reviews and recommendations in particular are outstanding.
  • My favorite science writer, Ed Yong, covered a lot of synthetic biology this month. He wrote about yeast biosensors to quickly and cheaply detect cholera; Kevin Esvelt’s efforts to employ gene drives to improve human health, protect endangered species, and change the way science is done; and on how Seth Shipman wrote a digital image and a GIF into the DNA of living bacteria by repurposing the memory part of the CRISPR immune system.
  • Newsweek ran a cover story about synthetic biology in academia and industry. A good one to send to your friends and family members who wonder what synthetic biology is all about.

Policy and Bioethics

  • The MIT Technology Review is reporting that human embryos have been edited with CRISPR in the US for the first time, by the lab of Shoukrat Mitalipov in Oregon. Moreover, it sounds like the new work has overcome technical hurdles related to editing efficiency and off-target cleavage. Rubicon, crossed.
  • An editorial in the Baltimore Sun by Gigi Gronvall argues that the US must redouble its investment in synthetic biology and biotechnology, in order to maintain its edge in the 21st century world economy.
  • This thought-provoking essay on Biopunk and Subverting Biopolitics from Heather Dewey-Hagborg, Simone Brown and Joerg Blumtritt is definitely worth reading.
  • The convergence of conservation and synthetic biology continues. The Audubon Society published an in-depth article exploring the potential of gene drives for protecting endangered bird species.

Biosecurity

  • Since FBI special agent Scott Mahloch is coming to talk to GeneMods, here’s a profile of his boss Ed You by the always-excellent Antonio Regalado.
  • The Pentagon has partnered with the National Academy of Sciences to review the threat posed and policy around synthetic biology research. What are they worried about? Among other things, stuff happening in Canada:
  • Not cool, Canada. A team at the University of Alberta lead by David Evans synthesized a horsepox virus (a relative of smallpox) from scratch for about $100,000 and 6 months of work. The purpose of this research was to learn to synthesize poxviruses as a possible way to kill cancer tumors, but it has prompted concern and discussion of dual-use in synthetic biology.
  • Not new news, but worth reading: this decade-old Technology Review article about the Soviet Union’s bioweapons development program, and the way the biosecurity community grapples with its implications. Particularly poignant given how precipitously the price, time and skill required for the molbio techniques described continue to fall.
  • DARPA just awarded grants from its Safe Genes program to seven teams. The awardees will attempt to develop technologies to make gene editing ‘safer’ by reducing, stopping, or reversing unwanted/dangerous edits. Particularly excited to see Kevin Esvelt’s team get funding to study self-limiting gene drives.

Industry and Funding

  • DuPont Pioneer has secured exclusive rights to agricultural use of Emmanuel Charpentier’s CRISPR IP, via a license from ERS genomics. However, it’s not clear how ‘exclusive’ these exclusive rights are, since Monsanto has already non-exclusively licensed CRISPR for agriculture from the Broad institute. Perhaps DuPont now owns all rights in Europe, while it will need to share with Monsanto in the US?
  • Google is getting into the engineered mosquito business. Alphabet subsidiary Verily has announced plans to grow and release (in California!) 20 million male mosquitos infected and sterilized with Wolbachia, a bacterium which prevents the bugs from producing viable offspring.
  • Speaking of mosquitoes, Oxitec has just signed a contract to release its genetically sterilized ‘Friendly Aedes’ mosquitoes in Brazil.
  • Maxx Chatsko writes that at current prices, it would cost ~$2 billion to make a 1 terabyte DNA-powered data server. Microsoft and others are betting on massive cost reductions in the next decade or two.
  • Gene therapy may get a lot cheaper and more mobile, thanks to Jennifer Adair.
  • Baker lab spinout company Arzeda just raised $12 million to grow its de-novo enzyme design business.

Now, on to the research papers!

Building Life From the Bottom Up

  • Life runs on proton gradients across cell membranes. Now, Ritzmann et al. have built a minimal system for generating these gradients, by fusing GFP to a light-driven proton pump, so that the pumps insert directionally into vesicles and can then pump protons into them.
  • Adding new letters to the code of life has unexpected applications. Kimoto and Hirao show that two hydrophobic, unnatural DNA bases, Ds and Px, can be copied and read with high fidelity, and that primers with Ds bases can sensitively detect single base mismatches in DNA sequences in a qPCR assay.

Biomolecule Engineering

  • Baker lab is getting even better at building proteins from scratch. This month, Rocklin et al. take advantage of high throughput DNA synthesis and a clever stability assay to synthesize and characterize the stability of thousands of small de novo designed proteins. With this giant dataset, they are able to iteratively improve their protein design algorithms. Where before fewer than 1 in 10 designs folded properly, by the end of this study almost half of all their new proteins fold as designed. Tour de force. Summary in phys.org.
  • Baker lab aren’t the only ones designing useful proteins! Terada et al. have built a three-lobed protein (and named it ‘Mitsuba’) which binds tightly and specifically to cancer cells expressing a sugar molecule called globotriose.
  • Folliard et al. have made better, more modular riboswitches that display consistent performance even when the gene they’re regulating is swapped out.

Genetic Circuits

  • Zong et al. are getting really good at programming genetic circuits. By developing libraries of insulated minimal promoter and operator sequences, they were able to reliably and rapidly build bacterial genetic circuits that performed almost exactly as modeled in the computer. Biology has rarely looked more like an engineering discipline than it does in this paper.
  • Gene circuits based on…chewing up plasmids? Baumgart et al. show that you can build a stable genetic oscillator based on two plasmids, where one drives expression from the second, and the second expresses a nuclease that destroys most copies of the first plasmid. DNA copy number is now (at least in E. coli) a dial you can use to dynamically tune genetic circuit performance.
  • Genetic circuits that function in multiple species can be very difficult to build. Xiao et al. have achieved that for a nitrogen sensor, demonstrating ammonium detection and response in three species of bacteria.
  • Super cool supercoiling. Yeung et al. show that the supercoiling of DNA at one gene’s promoter can significantly affect the expression levels of a nearby gene. They then take advantage of this property to build a better genetic toggle switch.
  • Computational biology? No, this is biological computation. Chatterjee et al. have built spatially localized DNA-based logic gates using DNA origami and hairpins. Turns out DNA compuation run on a scaffold works 35 times faster at 50 times lower concentration than equivalent systems with freely diffusing components. Summary on the Microsoft Research Blog.

Computational Biology

  • Levin et al. use genomic databases to propose a genetic toolkit for modifying Symbiodinium, photosynthetic dinoflagellates that live in coral cells. No wet lab work here, but maybe the basis for some in the future.
  • Amazon wrote a blog series about how to use their AWS cloud computing platform to analyze genomes. They claim that if you bid on secondhand/spare compute capacity, you can analyze an entire genome for as little as $1.
  • In this era of big biological data, how can you efficiently find the right enzyme from the right organism to catalyze the right reaction to make the molecule you want? Swainston et al. are here to help: they’ve built biochem4j, a searchable meta-database that combines information on small molecules, reactions that make them, predicted enzyme function and enzyme taxonomy from the UniProt, KEGG and NCBI Taxonomy repositories.

CRISPR and Gene Editing

  • CRISPR isn’t all gene editing! Shipman et al. from George Church’s lab show that you can use the DNA acquisition parts of this bacterial immune system to write digital data, including a picture of a hand and a GIF of a horse, into the genomes of live bacterial populations.
  • Doudna lab found an anti-CRISPR protein called AcrIIA4 that is a natural phage inhibitor of CRISPR. It binds to the sgRNA-Cas9 complex at the region of Cas9 that normally engages the DNA protospacer adjacent motif, blocking DNA recognition. They also found that timed delivery of the protein into human cells reduced off-target effects!
  • Jung et al. are CHAMPs at analyzing CRISPR complexes! They’ve shown you can take a used Illumina flow cell and perform massively parallel analyses of the binding propensities of fluorescently labeled CRISPR machinery. This technique should easily generalize to analyzing other DNA-binding proteins as well.

Therapeutic SynBio

The Strains, They Are A-Changin’

  • Hashimoto et al. have isolated a gene from a notoriously hardy tardigrade (water bear), and shown that it makes human cells more resistant to DNA damage from X-rays and hydrogen peroxide. If you wanted to engineer microbes, algae or humans to thrive in a high-radiation environment (like space, or Mars), this might be a good gene to splice in. News summary here. (This is from 2016?)
  • It can be hard to make lots of human proteins in bacteria, because the human proteins will misfold. Reyes et al. have made it a little easier now, demonstrating that adding lots sucrose to the culture and inducing osmotic shock enhanced the folding and expression of a human protein in E. coli.

Plant Engineering

  • Want a quick, cheap and easy way to make a plant resist drought? Douse it with vinegar. Kim et al. tried modeling and engineering the drought response pathway in Arabidopsis, and found out that acetic acid alone can induce a protective drought response in unmodified plants. This trick works in wheat, maize and rice, too. Who needs gene editing, anyway?
  • Reed et al. show that you can (relatively) rapidly make gram-scale quantities of previously uncharacterized molecules by transiently expressing the biosynthesis enzymes in tobacco plants.
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