SynBio Newsreel, April 2017

Blogs and community news

Policy and Bioethics

  • In an about-face, the FDA has approved 23andMe to supply users with information about their risks for various diseases. Previously, 23andMe was only allowed to provide information on diseases the users might be carriers for.
  • Researchers are taking more seriously the idea that humans will need to be genetically modified in order to colonize Mars and the rest of the solar system.
  • In the future, will some forms of gene editing be required? Intriguing article in The Atlantic draws comparisons between the prosecution of Christian Scientist parents for the avoidable deaths of their children, and a potential future in which parents are held accountable for not editing deadly diseases out of their children’s genomes.

Industry and Funding

  • At their London conference, SynBioBeta founder John Cumbers announces a new synthetic biology venture fund in partnership with Data Collective. If you need money for your synbio startup, now there’s one more place to apply.
  • The biohacking project to build a glowing plant has run out of money and had to stop. They’re still working on making a fragrant moss, however.

Books, Videos, Podcasts

  • Drew Endy’s keynote at SynBioBeta London was something else. No one can accuse him of not dreaming big.
  • The Naked Scientists (perhaps my favorite general science podcast) devote an episode to organs-on-chips. And if you don’t like listening, you can read the transcript.

Biosecurity

  • The SB7.0 conference is offering a Biosecurity Fellowship. Only a 1 page application, but it’s due on April 28th, so apply fast!
  • Labs are trying to use CRISPR as an antibiotic, delivered via bacteriophage to chop up the pathogenic bacteria’s DNA. It’s an interesting idea, but I wonder: if you’ve found a phage to deliver CRISPR into target bacteria, why not just use the phage to kill the bacteria?

Now, on to the research papers! Fewer than most months; I’ll try to find more in May.

Detection and Genetic circuits

  • Belkin et al. can find landmines from a distance with E. coli, in a field trial. Summary in The Guardian (though the paper is really short, so a summary is almost unnecessary).
  • Gottenberg et al. reveal SHERLOCK, a CRISPR/C2c2-dependent strategy to detect minuscule concentrations of specific RNA and DNA sequences. Summary in MIT News.

Therapeutic synbio

SynBio Newsreel, March 2017

Lots of things happened in March!

Blogs and community news

  • Aaron Dy discusses how the bionic leaves being developed in Pam Silver’s lab could aid in the colonization of Mars.
  • Daniela Quagliela interviews the founders of UK synbio company Synthace about Antha, the high-level programming language they developed to speed up and simplify automated bioengineering protocols.
  • Indiebio’s blog now has interviews with most of their portfolio companies. A great place to find synbio companies doing cool work!
  • Policy and Bioethics
  • Induced pluripotent human stem cells can now be patterned to generate structures that look a lot like early embryos. These synthetic human entities with embryo-like features (SHEEFs) will force us to rethink the decades-old rules surrounding human embryo research.
  • In ever greater numbers, parents are starting foundations and companies to develop gene therapies for the rare diseases that afflict their children.

Industry and Funding

  • Forbes profiles Craig Venter—what he’s done, what he’s doing, and what he hopes to do in the future.
  • eGenesis raises $38 million to engineer pigs that can serve as organ donors to humans.
  • Wired profiles two startups—Venomyx and VenomAB—that are trying to make cheap, recombinant snake antivenom. But will their approach be able to tackle antivenom’s distribution challenges?
  • Twist raises an extra $33 million to expand its gene synthesis, and DNA data storage and pharmaceutical discovery strategies.
  • If February was a great month for Broad in the CRISPR patent fight, March looks a bit tougher. The European Patent Office granted a broad (not Broad) CRISPR patent to University of California and University of Vienna (Doudna and Charpentier’s institutions), for developing the single guide RNA to guide Cas9.

Books, Videos, Podcasts

  • Radiolab devotes an entire episode to an update about CRISPR and gene drives, including interviews with Jennifer Doudna, Kevin Esvelt and the best (well, only) audio representation of a bacterial CRISPR repeat I’ve ever heard.
  • George Church gave an hour-long talk to the Innovative Genomics Institute. Worth watching!

Biosecurity

  • Bill Gates publishes an op-ed arguing that bioterrorism is a serious threat to global security, and that to counter this threat we must strengthen public health infrastructure in the developing world, increase our ability to rapidly generate new vaccines, openly share health/epidemiological data between countries, and ‘prepare for pandemics the way the military prepares for war.’ Interestingly, these steps are very similar to the global health goals his foundation has been pursuing for a while, just repackaged to emphasize the economic and security arguments for them. Perhaps this reframing will persuade the current US government to maintain or increase spending on global health?

Now, on to the research papers!

Genetic circuits

  • If most synbio takes steps toward making biology easier to engineer, Weinberg et al. just took a giant leap. They use recombinase-based genetic circuits to reliably build over 100 complex logic gates in mammalian cells, including a 6-input AND gate, and even adder and subtracter modules. It’s like Endy lab’s reliable, stable genetic programs in E. coli—but bigger, and in mammals! Summary in Wired.

Biomolecule engineering

  • Running out of colors to paint your cells for fluorescent imaging? Frances Arnold’s lab has your back. Herwig and Rice et al. engineered an opsin protein to accept a synthetic chromophore, so that it now fluoresces brightly in the infrared. Works in both bacteria and mammalian cells, too.
  • Bedbrook and Rice et al. from Arnold lab also take aim at engineering new light-activated ion channels for optogenetics, using recombination of diverse channelrhodopsin sequences to generate new proteins with distinct expression, localization, and light-induced activation patterns.
  • Praetorius and Dietz report DNA origami, with TAL effector staples!

Computational biology

  • Data storage in DNA just got much more feasible. Erlich and Zielinski combine fountain codes (a robust encoding strategy from mobile video streaming applications) and automated, iterative oligo sequence optimization to store 72 MB of data in easily sequenced DNA. They achieve unprecedented retrieval fidelity (100%), lossless copying capacity (a quadrillion replications), and storage density (250 petabytes per gram), approaching the theoretical limit for data storage in DNA.

Gene Drives and CRISPR (also, preprints are cool)

  • One of the primary ethical challenges confronting gene drives is that, even if the population of one region supports drive use, the drive could easily spread to areas where people don’t want it. In a new preprint, Min et al. from Kevin Esvelt’s lab propose a technical solution to this problem of universal consent: a daisy quorum gene drive. This system combines the limited spread of a daisy chain gene drive with a genetic ‘quorum sensing’ capability, so that after the daisy drive runs out of gas, the drive modifications are only stable in regions where most of the target organisms have already been modified. This architecture also enables a second gene drive to revert a modified population to the wild genotype, increasing the potential reversibility of gene drives.
  • Efficient editing with CRISPR is a challenge, so it would be great if you could just select for the cells that have been edited. Well, now you can! Agudelo et al. report on Biorxiv a method to select for edited cells by co-delivering guide RNAs which generate toxin-resistant mutations in a sodium/potassium pump gene.

The strains, they are a changin’

  • Saccaromyces cerevisiae 2.0, the yeast with a synthetic genome, is more than halfway complete. 7 articles detailing Boeke and company’s progress appeared simultaneously in Science. Pretty frickin’ cool.

SynBio Newsreel, February 2017

I’ll put the videos up here as well once they upload. Enjoy!

Blogs and community news

  • PLOS Synbio has an excellent interview with Christina Agapakis, creative director at Ginkgo.
  • STAT profiles Jeantine Lunshof, the bioethicist embedded in George Church’s lab who makes sure they don’t rush too quickly into ethically questionable research.
  • SynBioBeta highlights five women CEOs of synbio companies.
  • Keith Robison of OmicsOmics has an excellent perspective piece on Gen9’s acquisition by Ginkgo and the challenges of the high throughput DNA synthesis business, with a bonus appearance by Gen9 CEO Kevin Munnelly in the comments section.
  • Bioscentric argues that synthetic biology can bridge the coming ‘protein gap’ (disparity between available supply of protein and demand for it by global middle class) by engineering plant-based meat substitutes to taste and feel more like the real thing.

Policy and Bioethics

  • The National Academy of Science’s report on the ethics of human embryo editing, a year in the making, argues for cautious use of germline editing, for diseases which have no “reasonable” therapeutic alternatives, and following much more research into safety and efficacy. Notably, while the report advocated against genome editing to enhance embryos ‘at this time,’ it rejected the argument that genetic enhancement would be likely to significantly increase societal inequality. This comes after the American College of Medical Genetics urged against clinical editing of embryo genomes, at least until further ethical and technical issues are addressed. NAS’s report seems to be running a little ahead of public sentiment, according to a recent Pew poll which showed a majority of Americans are more worried than enthusiastic about genome-edited babies.
  • The FDA curbs a biohacker’s plans to use CRISPR correct a genetic disease carried by purebred dalmatians. He may just do it anyway, though.
  • India doesn’t have an official government policy on synthetic biology, but that’s about to change.

Industry and Funding

  • The patent for using CRISPR in eukaryotes belongs to the Broad institute, according to the Patent and Trademark Office. Expect UC Berkeley to appeal, but this is a major blow to their legal claim that gene editing with CRISPR in eukaryotes is an obvious extension of Doudna and Charpentier’s work in vitro and in bacteria. Berkeley professor and soon-to-be Senate candidate Michael Eisen wrote a scathing critique of the decision, and of University patent rights generally.
  • Meanwhile, the Innovative Genomics Institute (run by UC Berkeley and UCSF) intends to invest $125 million into gene editing research on crops and microbiomes. That’s a lot of CRISPR!
  • IndieBio graduates its fourth class of startups (full demo day video here). Among them are companies specializing in DNA data storage, enzyme engineering, high-throughput embryo editing, and microfluidic cell culture devices.
  • A year later, Twist Bioscience responds to Agilent’s lawsuit alleging IP theft.
  • You can now buy CRISPR-Cpf1 for gene editing from IDT.

Books, Longreads, Podcasts

  • Society needs to prepare for The End of Sex (for reproductive purposes), according to the book of the same name written by Stanford Law professor Hank Greely. Greely predicts this shift will be causes by the convergence of two technologies, in vitro generation of gametes from induced pluripotent stem cells and pre-implantation genetic diagnosis (PGD). These technologies will soon combine into a simple procedure called Easy PGD that enables parents to generate thousands of zygotes in vitro, implanting only those which have been sequenced, screened and edited to prevent genetic disorders (and, potentially, select for non-disease traits). The book provides a good overview of the scientific progress on both technologies, and extensively explores the legal, ethical and social implications of Easy PGD. I highly recommend it.

Biosecurity

  • Devang Mehta argues in an excellent PLOS Synbio post that biosecurity threats from DIY biohackers are overblown (for now), while threats from state actors are potentially more serious.
  • Former Ventria Biosciences employee Weiqiang Zhang is convicted of attempting to steal a genetically modified rice strain.

Now, on to the research papers!

Biomolecule engineering

  • Pu et al. use continuous, directed evolution to build a split RNA polymerase whose activity is dependent on the dimerization of modular protein-protein and small molecule binding domains. Basically, constructing a genetic sensing/actuation circuit from two interacting or molecule-binding protein domains just got a lot easier. Really cool.
  • Does Baker lab just publish a Science paper every month at this point? Marcos et al. have figured out how to build proteins from scratch with surface cavities structured around distorted beta sheets.
  • The last restriction enzyme you’ll ever buy? Enghiad and Zhao use a thermostable, DNA-guided nuclease called PfAgo to generate artificial restriction enzymes which can cleave any sequence while leaving sticky ends of any sequence at the cut sites. Summary in GEN.
  • Quagliela et al. use Golden Gate cloning to combine multiple different mutagenesis strategies in a single protein engineering library.

Genetic circuits and Metabolic Engineering

  • Gupta et al. apply quorum sensing to metabolic engineering, constructing strains of E. coli that switch off essential glycolytic enzymes when they reach a high enough density, thereby increasing the output of chosen metabolites derived from central carbon metabolism. Summary in MIT News.
  • Engelen et al. augment the field of DNA-based computing by debuting antibody-templated strand exchange, a process by which antibodies initiate the strand displacement reactions of peptide-functionalized DNA strands. They show how antibodies and their cognate antigens can now be used as inputs for DNA computing circuits.
  • Wearable computing is cool, but how about wearable, living computing? Liu et al. use a printed silicone/hydrogel combination material to construct simple wearable devices into which engineered E. coli can be embedded and subsequently sense small molecules on the surface of the skin.
  • Want to learn more about optogenetic control of gene expression in budding yeast? Then this review by Salinas et al. is for you.

Photosynthetic Synbio

  • Higo et al. build RNA-based, small molecule-inducible genetic circuits in cyanobacteria, thereby adding a modular and portable tool to the sparse cyanobacterias toolbox.
  • Song et al. show that new, fast-growing cyanobacterium UTEX 2793 can be engineered to produce more sucrose and glycogen than any strain before it. This is actually a paper from last year that got caught in my NCBI crawler, but it was relevant to Quentin’s November presentation so I thought it was worth adding.

Computational biology

  • Model and build biology to understand it! Moreno-Fenoll et al. explore how microbial communities that rely on commonly produced resources can survive the emergence of ‘cheaters,’ which consume the common resource without producing it. The show through mathematical modeling and engineering a synthetic microbial community with ‘cheater’ and ‘cooperator’ strains of E. coli that spatial division of the community into many random sub-populations promotes recovery of the cooperators after a cheater-induced population crash.

The strains, they are a changin’

  • Agmon et al. generate biocontained yeast by placing several essential genes under small molecule-inducible promoters, such that the strains won’t grow in the absence of, for instance, estradiol. They also demonstrate a strategy to dope in ‘decoy’ small molecules which don’t affect cell viability but make it harder for biopirates to figure out which small molecules are required to make the strains grow.
  • Two papers on improving the expansion of the genetic code, both from UT Austin labs! First, Monk et al. showcase a dual fluorescent protein reporter which can rapidly quantify the activity and specificity of non-standard amino acid (nsAA) incorporation by orthogonal tRNAs, and also an evolved, faster growing variant of the amber-codon-lacking recoded E. coli strain developed in Church lab. Maranhao and Ellington simultaneously debuted a new positive/negative selection strategy to develop more active and specific orthogonal tRNAs. They also show that non-recoded E. coli expressing their improved tRNAs grow faster than strains expressing the original tRNAs (recoded E. coli grows the same either way).

Therapeutic synbio

The CRISPR Patent Battle

For this month’s main presentation, Albert Xue gave a comprehensive and entertaining overview of the patent interference proceedings between UC Berkeley and the Broad Institute over the patents for using CRISPR to edit eukaryotic genomes. Watch below, and feel free to comment if you have additional insights/opinions about this patent battle.

SynBio Newsreel, January 2017

Happy new year, synbio community! And also happy first anniversary of this blog, approximately. Joe Muldoon gave an excellent summary of the newsreel at today’s meeting; watch below, and then continue to the full linkstorm!

Synbio community news

Synbio profiles

  • Ginkgo Bioworks co-founder Tom Knight appears in Forbes. Main takeaway: it’s never too late to go back to school and learn a new field.

Industry news

  • Editas licenses CRISPR-Cpf1 exclusively from the Broad institute for therapeutic applications, and non-exclusively to Monsanto for agricultural applications. Meanwhile the Doudna-Charpentier CRISPR teams have pooled their resources, with Intellia, Caribou, CRISPR Therapeutics and ERS Genomics all signing a mutual patent sharing and protection agreement.
  • Oh snap! Ginkgo Bioworks acquires Gen9. This insightful Boston Globe commentary explains that the acquisition happened in large part because Gen9 ran out of funding in the cutthroat DNA synthesis market. Meanwhile, it looks like Ginkgo is trying to become the first vertically integrated synbio company. What will this mean for Twist Bioscience, now that their largest customer has bought its own DNA synthesis company?

Books, Longreads, Podcasts

  • Nick Lane’s The Vital Question, which tackles the origins of both life and eukaryotes, is excellent. Fun fact from the book: multicellularity has independently evolved over 30 times, but endosymbiosis between prokaryotes (the origin of eukaryotes) has only given rise to complex cells once, as far as we know.
  • Clarkesworld Magazine’s podcast is just what any sci-fi fan could want—a new short story (~20-90 minutes), read into your ears, every week. Lots of synbio speculative fiction here; I particularly enjoyed a recent episode (text version here) about two friends who make counterfeit steaks in China using high-end cell culture.

And now onto the research articles!

The strains, they are a-changin’

Biomolecule engineering

Genetic circuits and Metabolic Engineering

  • To increase bioplastic production, He et al. engineer a genetic circuit that turns on only when high density (measured by quorum sensing) and stationary phase are reached.
  • Crocker et al. use TALE protein fused to activator and repressor domains to develop a fully synthetic transcriptional regulation system in fruit flies. They then use this platform to explore the function of the pioneer/transcriptional enhancer Zelda, and to determine the best genetic architecture for generating sharp boundaries at the intersection of two developmental signaling factor gradients.
  • Maurer et al. compare lab yeast with industrial yeast using quantitative trait loci (QTL) mapping, figure out the alleles which matter most for the industrial yeast’s productivity, and use CRISPR to put those alleles into lab yeast. The result is a lab yeast strain which outperforms the original industrial strain!

Plant Synbio

CRISPR/gene editing

  • Anti-CRISPR proteins discovered by Rauche et al. inhibit spCas9 activity, and may facilitate biocontainment and reduce off-target effects of CRISPR applications. GenomeWeb has the summary.
  • Two new, compact CRISPR systems, dubbed CasX and CasY, discovered in uncultured archaea by a team including Jennifer Doudna. Their biochemistry and potential for genome editing applications should follow shortly, so watch this space! GenomeWeb has the summary.
  • This is genetics on CRISPR. Peters et al. use an inducible CRISPRi library to produce a powerhouse study of essential gene knockdown and function in B. subtilis. One of those fun papers where the new results barely fit even in a Cell paper.

Computational biology

  • Obertorner et al. from the Joint Genome Institute debut BOOST, a web design program for genetic parts that can modify sequences to make them easier/cheaper for for DNA synthesis companies to build.
  • Gumulya and Gilliam present a really cool review of how sequence data from diverse evolutionary branches of life can be used to reconstruct approximate ‘ancestral’ enzymes, which are useful both for evolutionary biology and as starting points for protein engineering studies.

Engineering mammals

SynBio Newsreel, November

Hey look, we figured out how to embed video! Now you can watch a newsreel summary first, and then read any of the papers that sounded particularly interesting. There are fewer links this month because work in November+December was crazy, but rest assured the January newsreel will be just as exhaustive as usual!

Synbio community news

  • Who needs CRISPR gene drives when you have Wolbachia? Scientists have successfully engineered the microbe, which lives in insect cells and spreads to all female offspring (while killing males), to render mosquitos inhospitable to dengue virus.
  • The GP-Write white paper came out. STAT summarized it.
  • iGEM happened! Many cool things. Grand prize winner was Imperial College London’s team, which engineered different strains of E. coli to co-culture at different population ratios.
  • This year’s iGEM saw the launch of bionet, a P2P sharing platform for biological materials developed through the Biobricks foundation and a Drew Endy-led team.
  • The Wyss Institute’s work on replacing animal drug testing models with human organoids on chips gets a write-up in Wired.
  • UK researchers apply to perform field trials on wheat that has been modified to photosynthesize more efficiently, boosting yields 20% (in a greenhouse).

Industry news

  • The Guardian profiles BioAmber and Bolt Threads, two companies trying to develop yeast-based pipelines for succinic acid and spider silk fabrics, respectively.
  • PacBio sues Oxford Nanopore for infringing patents related to reading a single DNA molecule twice. OmicsOmics argues this lawsuit probably won’t damage Oxford Nanopore’s business, and is more an act of desperation from PacBio.

Now, on to the research papers!

Biomolecule engineering

CRISPR/gene editing