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

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

SynBio Newsreel, September

Lots of news this month. We’ll post a link to the video version of the newsreel later this week. Enjoy!

Synbio community news

Biosecurity

Industry news

Longreads

  • The snakebite crisis is escalating. Synbio could help—but it needs to avoid distracting from lower-tech initiatives, like scaling antivenom production in Africa and giving farmers boots.
  • A thought-provoking history of DNA data storage, which also outlines the challenges and opportunities ahead for the field.
  • In-depth analysis of the medical/pharmaceutical biotech investment ecosystem, from Brady Huggett.
  • Freeman Dyson writes an inspiring vision of biology’s place in space exploration.
  • The Summer 2016 edition of BioCoder is out (free PDF download if you register). Read it if you’re interested in DIYBio and synthetic biology from the perspective of hackers and makers.

Video

Non-synbio blog of the month

  • Genotopia is Professor Nathaniel Comfort’s blog about bio, genetics, medicine, history, and hype in biotech. His recent trilogy of posts about going to Yellowstone hot springs to study the origin of life is definitely worth reading.

Now, on to the research papers!

Biomolecule engineering

Genetic circuits

CRISPR/gene editing

Metabolic engineering

Building biology to understand it

  • Yizhi Cai and Roy Walker summarize the results from the Fifth Annual Sc2.0 meeting, providing updates on the Synthetic Yeast Genome Project, and renewed debates about the Human Genome Project-Write.
  • Review article argues that synbio could help to predict new biochemical innovations life may experience in the next few billion years. It’s an interesting perspective through which to view the field, and discusses cool work on improving photosynthesis and rewiring central carbon metabolism.

Autotrophs and agriculture

Therapeutic synbio

The strains, they are a changin’

    • A team led by Dan Gibson engineers Vibrio natriegens, which grows 2-3 times faster than E. coli, into a platform for plasmid cloning and protein expression. The design-build-test cycle in biology is about to get significantly faster.