Category: Uncategorized

June/July Newsreel

Hi folks! We haven’t been updating the blog in awhile, but we’re back to give you some updates in the world of synthetic biology (with links)!

Policy/Popular News

  • Last Week Tonight covered CRISPR gene editing in a recent episode. With interviews from Jennifer Doudna, George Church, and Kevin Esvelt, we think it’s a pretty good watch.
  • The FDA approved golden rice!
  • Controversially, the EU now includes gene-edited crops and animals under the umbrella of GMOs (which previously only meant organisms with recombinant/foreign DNA inserted). This will lead to more regulations of gene-editing in Europe and have a huge impact on research there.

Industry News

  • Here’s an article about the rise of Oxford Nanopore and how Illumina is burying their head in the sand about it.
  • Programmable, enzymatic synthesis of DNA from scratch is finally becoming a reality! Keasling lab just published a proof-of-concept paper demonstrating one method, and startup DNAscript reports that their enzymatic oligo synthesis has reached 50 nucleotides!
  • Our Lanzatech neighbors over in Skokie have launched their first waste gas to ethanol plant in China! If you don’t know, they use Clostridium autoethanogenum to convert carbon monoxide to ethanol and eventually other useful products.

Gene Editing

  • Lots of CRISPR news recently. First, in June, a paper in Nature Medicine claimed that CRISPR activates the p53-mediated DNA damage repair system in human tissues, which is a pretty big problem. Also, a paper in Nature Biotech in July by Allen Bradley claims CRISPR causes much larger off-target deletions (several kilobases!) than previously thought. Do these claims hold up? Will they apply to the upgraded CRISPR enzyme variants, which are engineered to greatly reduce off-target effects and perform editing without introducing double strand breaks? Time will tell.

Research

  • I think this paper is super cool. The Anderson lab used circular RNAs to reduce degradation and improve protein yields from translation by 800% more than unprotected mRNA and 50% more than mRNA protected from degradation by other methods.
  • Northwestern synbio alert! Here’s an update from a Mrksich/Jewett/DeLisa lab collaboration. One-pot cell-free synthesis of glycoproteins!
  • Selenoproteins are cool! The Ellington lab evolved some recoded E. coli strains to incorporate selenocysteine into proteins to form diselenide bonds, which are more stable than disulfide bonds.
  • There are SEVEN, count ’em, seven papers out about advances with SCRaMbLE, gene shuffling/duplicating/deleting capability installed by the synthetic yeast genome project, Sc2.0. Here, here, here, here, here, here, and here.

 

 

Synbio Newsreel, January 2018 (pretty late)

Hi folks! Sorry we haven’t updated in a while but we’re back with more synthetic biology news! Here’s some of what we talked about at our January meeting.

Podcast news- we have a great new episode of the GeneMods Podcast in case you missed it! Here’s a SoundCloud link, but you can also find it wherever you get your pods by searching “GeneMods” (and be sure to subscribe!). We have decided to split up the news and interview sections so we can bring you more content. This month, Isaac Larkin and Adam Silverman square off and answer Jordan Harrison’s questions–we will likely rotate who’s competing on each episode.

There was some great pop-sci attention to synthetic biology in the news in January/late December:

  • Here’s a great article in the New York Times about David Baker’s designed, “artisanal” proteins.
  • I’m generally a fan of The Atlantic’s science writing. This article talks about a new method of eliminating primer bias in sequencing 16S rRNA to identify new microbes. (We’ve only sequenced about .0002 percent of the microbial diversity on Earth.)

In policy news, the FDA issued a somewhat stern warning to biohackers in a press release emphasizing that the sale of untested, self-administered gene therapy kits is illegal.

And finally, here’s some research news:

  • A team led by Farren Isaacs got MAGE working in yeast for the first time.
  • Oxford Nanopore directly sequenced RNA without needing reverse transcription.
  • Uh oh. A preprint from the Porteus group claims CRISPR provokes an immune response in humans.
  • Here’s a cool paper about using biochemically-altered indigo as a greener, less toxic dye for garments.
  • Mike Jewett and Chris Voigt wrote a commentary in Nature Chemical Biology about needing an orthogonal framework for central dogma (with a lot of computer analogies) to solve the problems of transferring biological “programs” between organisms and reworking central dogma processes themselves in a way that doesn’t upset the balance of the whole system.

That’s all for now, we’ll see you at the next meeting!

Syn Bio Newsreel, December 2017 (a lot late)

Hi everyone, while we’re doing a backlog of blog posts, here’s the news from December! Enjoy!

GeneMods Podcast

-In this month’s podcast, we interview Karmella Haynes about her lab’s work in chromatin engineering to control gene expression. You won’t want to miss it!

Blogs and Community News

-The iGEM Jamboree was a huge success! Read here about the winners, particularly first place Vilnius’ on a novel way of regulating plasmid copy number in cells. Also, check out PLOS SynBio Community for a judge’s first-hand account of the competition.

-SynBioBeta reports on “Five Wild Biotech Products That Will Touch Our Lives in the Near Future”. We’re ready for you, cow-free cow milk and post-animal burgers. Mushroom lamps…maybe not.

Policy and Bioethics

–        In MIT’s Technology Review, Emily Mullen outlines all the CRISPR clinical trials set to happen in the US in 2018. CRISPR Therapeutics, the company founded by Doudna, Charpentier, et. al., will aim to use the genome editing technology to treat sickle cell anemia.

Industry and Funding

–        With its latest 275 million dollars in venture capital, Ginkgo Bioworks is now the first synthetic biology “unicorn” valued over a billion dollars.

–        An economic analysis of the feasibility of microbe-brewed spider silk reveals that E. coli­-sourced protein could one day get as cheap as $23/kg. That same mass requires more than 5,000 silkworms to produce.

–        Also speaking of spider silk, Wired frequently has some good syn bio coverage; here’s an article about Bolt Threads’s 100 spider silk beanies (which sold out immediately).

Cell-Free Synthetic Biology

–        PURE Express is great, but purifying each of the individual components for transcription and translation means that it carries a heavy price tag. This month, a group has published on engineering synthetic microbial communities that specialize in producing each of the components in bulk, greatly speeding up the purification process and, hopefully, tamping down that price tag.

  –        Then again, if you do want to mess around with messy extract systems (and who wouldn’t?), Jim Swartz and Jeffrey Varner have pre-published a useful summary on BioRxiv for independent sequence-specific modelling of transcription and translation in cell-free conditions.

Biomolecular Engineering

–        In the culmination of 20 years of effort, Floyd Romesberg’s group at Scripps has managed to create a strain of E. coli that can stably maintain a pair of unnatural nucleotides (labelled “X” and “Y”) in a plasmid and transcribe and translate them into a protein containing a nonstandard amino acid. A follow-up paper in JACS reveals that the mutations can be stably inherited on the bacterial chromosome.

–        There are protein scaffolds, DNA scaffolds, RNA scaffolds, but how about lipids? A new paper out of the Silver lab shows that you can colocalize metabolic enzymes to synthetic lipid assemblies to enhance yield of indigo.

Gene Circuits

–        Liu et. al. discuss just how tricky it is to get copy number right to prevent metabolic burden when expressing even simple AND gene circuits in E. coli. Can RNA-seq be a useful diagnostic tool to help?

–        Not sure about the acronyms, but the concept is pretty dang cool; Stanley Qi’s lab has reworked their previous Tango system to design ChaCha, a way of fusing diverse G-protein coupled receptors to a functional output based on dCas9 repression of a target gene.

–        The Smolke lab has applied miRNA switching to a real therapeutic target: T-cell proliferation. Adding a small molecule drug turns on cytokine signaling pathways. Read about it here:

De novo Protein Design

–        Enzyme design just keeps getting better and better; this month, Nature Communications reports the design of 4 alpha-helix bundles for a highly active and promiscuous oxidoreductase.

–        Not to be outdone, David Baker’s Nature paper of the month involves the engineering of a synthetic viral capsid that encapsulates its own DNA. These capsids had similar packaging efficiency to adenoviruses commonly used for gene delivery. Crazy stuff.

Build-a-Bear… with DNA???

–        December was a great month for DNA origami. First, we found out about a simple way to make mg-scale amount of DNA in standard 1L lab fermenters using phage and self-cleaving DNA sequences interwoven between arbitrary DNA sequences. Then, Peng Yin’s group showed that gigadalton-scale assemblies of 10,000 DNA parts can be achieved by using 13-nucleotide binding domains. What was the first thing they chose to make? A teddy bear, of course.

SynBio Newsreel, September 2017

GeneMods Podcast

  • We interviewed Drew Endy about the Biobricks Foundation’s 10K Genes project, an unprecedented initiative to synthesize 10,000 genetic parts and and make them all freely available to the public. Biotechnology and synthetic biology will be changed forever by this project. Interview also available on iTunes and Stitcher.

Blogs and Community News

  • SynBioBeta is next month, and Vinod Khosla and George Church will give a fireside talk about the intersection of AI and syn bio which should hopefully be online. Watch this space.
  • It’s Everyone’s Favorite Science Writer Ed Yong, with a cool article about kakapos–large parrots from New Zealand–and how they are the first species on Earth where every single individual has had their genome sequenced (granted there are only 153 of them).

Policy and Bioethics

  • Not a good month for Craig Venter in general: Synthetic Genomics is being sued for gender discrimination after some very off-color remarks made to a female exec–follows up from a similar incident in July at the Salk.
  • SynBioBeta, OTOH, is proudly parading the female representation in execs in the syn bio space at their October conference…

Biosecurity

  • The National Academies of Sciences, Engineering, and Medicine has a report out about security concerns in synthetic biology.

Industry and Funding

  • Novartis’ CAR-T cell therapy got approval from the FDA, but it costs $475,000, raising the question of how patients will pay for it and other similar therapies. The same NYT writer even contrasts it with the shrinking cost for other cancer treatments.
  • IndieBio, an incubator for synthetic biology startups, is graduating its fifth class of new companies. Here is a list of all the participants.
  • Here’s a Wired article about Gingko Bioworks teaming up with Bayer to make nitrogen-fixing bacteria that can colonize the roots of any plants, aka living fertilizer. Super cool!
  • Provenance Biofabrics has teamed up with Dr. Zev Gartner at UCSF in the goal to make synthetic leather using self-directed assembly of recombinant collagen. SynBioBeta has the full story.
  • Looking to make some cash? Michael Santoli at CNBC points out that the life sciences subsector of the S&P (incl. ThermoFisher, Illumina, Agilent, etc.) is outperforming FANG (Facebook, Amazon, Netflix, Google/Alphabet), 41% gain on the year compared to 36%. Take that, tech industry!
  • Eligo Biosciences gets a $20 million investment to pursue genome editing microbiome therapeutics.

 

Now, on to the research papers!

 

Cell-Free SynBio

  • The Jewett lab has a nice review paper out about engineering ribosomes.
  • The Coleman lab demonstrates production of an outer membrane protein from a mice-infecting strain of chlamydia to serve as a precursor for vaccine development. 1.5 mg/mL in a bacterial lysate…not too shabby!
  • If you want a synthetic minimal cell, you need a way to make phospholipids from fatty acids. Exterkate et. al. use just eight reconstituted and purified membrane enzymes to achieve continuous production of phosphoethanolamine and phosphatidylglycerol.
  • Lots of cell-free work in making protein biologics: check out the expression of antibodies and ScFvs membrane proteins in CHO lysates, plus on demand manufacture and purification in 1 day.

Biomolecule Engineering

  • Speaking of the Jewett lab, check out this book chapter in Methods in Enzymology with all you ever wanted to learn about engineering OSTs, ft. Jazzy and Jess!
  • It seems like every month progress accelerates in Baker lab’s work building proteins from scratch. This month, they designed, synthesized and characterized over 10,000 small proteins to bind to an influenza coat protein and botulinum toxin. They found hyper-stable designs that nullify botox toxicity and protect mice against influenza infections. Incredibly, these little proteins didn’t provoke an immune response in the mice, perhaps because they’re so stable that proteases can’t chew them up into fragments that the adaptive immune system can grab and recognize. Insanely cool.
  • A pretty neat review in Nature Drug Discovery on applications of directed evolution for making biosensors and identifying better binders or producers.
  • Remember Hal Alper’s talk about high-throughput evolution of secretory phenotypes in droplets using riboswitches as reporters? Well, it just got published in Nature Comm.

Genetic Circuits

  • Kubiak et al. created a synthetic circuit to unlink environmental stressors such as DNA damage from stress responses in the bacterial SOS gene network.
  • The Bennett lab at Rice shows that if you put two transcriptional circuits in series, the time to respond is the sum of the times for each individual circuits. In case you ever wanted to know how long lac operon induction takes, this one’s for you.
  • Rodrigo et. al. do some elegant work to engineer cascades and feedback loops using only RNA toehold switches to make hybridization networks.

Computational Biology

  • Craig Venter and friends published a paper in PNAS claiming to identify people’s faces using whole genome sequencing, which was almost immediately panned through BioRxiv…and Twitter. This is the kind of thing preprints are for!
  • Seventeen years later, and we’re still arguing about the repressilator. Some math from Imperial College, London shows that it can be redesigned for independent modulation of frequency and amplitude. (Does it work? Who knows!)

CRISPR and Gene Editing

  • Here’s a cool paper about using CRISPR to make better reporters by editing endogenous genes with luminescent peptide tags.
  • Engineering herpes simplex viruses--what could possibly go wrong? Turns out, a lot…unless you put the pieces together in 11 strains of yeast. Could be a really helpful technique in future viral gene delivery applications.

Therapeutic SynBio

  • These researchers used an engineered strain of E. coli with a genetic toggle switch as a tool to study infection and response to antibiotics in mice.
  • The Haynes lab has a cool paper up on BioRxiv about engineering synthetic mammalian transcription factors to upregulate silenced tumor suppressor genes in breast cancer cell lines. (Extra awesome because we just interviewed her for the podcast!)
  • A new RNA-targeting Cas9 is perfect for preventing the repeat expansion of microsat sequences in diseases like Huntington’s and MD–and it can be packaged into adenoviral vectors, too!

The Strains, They Are A-Changin’

  • Genome engineering on Corynebacterium glutamicum: some industrial biologists in Germany report deletions of 13% of the genome of the organism without impacting growth rate, making it an even better chassis for making amino acids.

Other

The Kaufman lab used a synthetic biology approach to make mutant H3 histone heterodimers to study exactly what histone modifications are required for transcriptional regulation.

Syn Bio Newsreel, August 2017 (kinda late)

Blogs and Community News

  • There was understandably a flurry of blog posts after the big CRISPR embryo editing news in July. Here is a very good one from James Kath, formerly of the Jewett lab, about how editing embryos with CRISPR has no real advantage over pre-implantation genetic diagnosis.
  • You may have seen this New York Times quiz, “Can Gene Editing Really Do That?” This is a great one to share with friends and family.
  • Contribute to the 10K genes project! Drew Endy and the BioBricks Foundation are partnering with Twist Biosciences to make 10,000 crowd-sourced genes publicly available and free. You can find out more information and suggest genes to order on their Reddit page.

Biosecurity

  • Apparently, researchers at the University of Washington made a computer virus out of DNA that launched when the DNA was sequenced. Interesting security implications…

Industry and Funding

  • Synthetic Genomics made a “digital-to-biological converter”…a kind of sequence to DNA to protein fax machine. This was the first time this has been done automatically only with computers and no humans. It has fairly typical applications like printing on-demand personalized medicines, but Craig Venter thinks it could be used to transmit biological information between planets!
  • After 25 years, AquaBounty Technologies has finally started to sell its genetically-modified salmon in Canada. It grows twice as fast as regular salmon, and is the first genetically-modified animal to be sold on the open market for food consumption. (It was the first animal to be approved for consumption back in 2015.)
  • More food news–Impossible Foods, the meat substitute syn bio company, is running into trouble getting soy leghemoglobin, the ingredient that allegedly makes their burgers taste like meat, approved by the FDA.

Now, on to the research papers!

Cell-Free SynBio

  • Jeff Hasty’s lab has a new system for rapid preparation of cell-free lysates from various bacteria.
  •  Tom Ellis’s lab developed a cell-free assay and computational model to predict the growth burden on E. coli cells for a variety of different proteins.

CRISPR and Gene Editing

  • Chunyu Han and colleagues officially retracted their paper in Nature Biotechnology that claimed to show NgAgo can be used as a gene-editing tool, because no one can replicate these findings. Here is Nature’s justification.
  • What is this? A CRISPR for ants?!  Two research teams independently edited two different ant species for the first time and knocked out their ability to smell pheromones,  completely changing their behavior to be less hive-mind and more individualistic.

Genetic Circuits

  • A group of researchers including Pam Silver and James Collins created a complex genetic logic circuit using ribocomputing devices.
  • The Golden lab at the University of California San Diego developed some cool synthetic NOT gate circuits in cyanobacteria. Good to have some more tools for cyanobacterial engineering.

Therapeutic Syn Bio

  • (Also CRISPR) Researchers inactivated all of the porcine endogenous retroviruses, or PERVs (oof, bad acronym), in a pig cell line toward the eventual goal of preventing transmission of these retroviruses during xenotransplantation of pig organs into humans.

 

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.

SynBio Newsreel, June 2017

GeneMods has a podcast now!

  • For the first episode, we interviewed Professor Danielle Tullman-Ercek about synthetic biology in space. We also run through some of the May newsreel, gameshow-style!

Other Podcasts

  • In Our Time, the BBC’s history podcast, devotes a whole episode to enzymes: how they were discovered, why they’re amazing, and what we use them for. Well worth a listen.

Videos

  • Josiah Zayner, biohacker extraordinaire, gave a riveting opening presentation at the Festival of Genomics in San Diego. Three thoughts after watching it: I want to know how he built a fully furnished lab for only $5000; I want to see the data confirming that he’s been able to genetically modify his skin cells; and I really felt iffy about the part where he implied that he was helping a guy treat his wife’s cancer.

Books

  • I just read (well, listened to) Change Agent, a new thriller by Daniel Suarez set in a biotech dystopia. An interpol officer in charge of hunting black market embryo editors in Southeast Asia gets dosed with a Change Agent, and finds his appearance and DNA fingerprint transformed into that of the very kingpin he has been chasing. It’s a richly imagined world and a fun read for anyone interested in synbio. The ‘mirror man’ assassin is my favorite character–you’ll have to read it to find out why!
  • Haven’t read the whole thing yet, but the first chapter of Cory Doctorow’s new scifi/spec-fic novel Walkaway opens with a party serving genemod fluorescent beer (which is already a thing, thanks to Josiah Zayner). On my reading list!
  • John Cumbers of SynBioBeta is teaming up with Karl Schmieder to write What’s Your Bio Strategy, a book about the massive advances in bioengineering and the synthetic biology entrepreneurs these advances are enabling. The book isn’t available yet but the site linked above contains numerous excerpts, comprising interviews with leaders in the synbio industry. One to watch for!

Big Conferences

  • SB7.0, the 7th iteration of the largest meeting in the field, took place in Singapore. There haven’t been a lot of recaps posted online, but I’m sure there will be more in July. The most exciting announcement I saw came from bionet, the organization Drew Endy helped start to facilitate the open sharing and modification of biological molecules, tools and protocols. The Biobricks Foundation is partnering with Twist Bioscience to synthesize and share, free of charge, 10,000 genes with the entire synthetic biology community. This unprecedented biotechnological commons will be available to anyone to use, modify, share and sell through the bionet license. Which 10,000 genes? You decide! Bionet will create a forum through which the whole synbio community can advocate for parts to go into the commons (perhaps through this subreddit). You can bet that GeneMods will do what it can to help build this new resource. I can’t wait to get started.
  • Busy month for synbio conferences! The week after SB7.0 in Singapore, Vancouver hosted the Synthetic Biology: Engineering Evolution and Design (SEED) conference. Many GeneMods members attended, and this month’s meeting includes a recap of their favorite SEED talks.
  • CRISPR 2017 happened in Big Sky, Montana. Michael Chao wrote a good overview in Nature Microbiology. The conference apparently featured positive mouse data from Locus and Eligo Biosciences, two companies trying to redirect CRISPR to kill antibiotic-resistant bacteria.

Blogs and Community News

  • The always-excellent Daniela Quagliela over at PLOS Synbio interviewed Julie Legault, the founder and CEO of bioengineering-in-a-box company Amino Labs.

Industry and Funding

Now, on to the research papers!

Small, Cheap, and Open

  • Microfluidics are going open-source. Kong et al. debut Metafluidics, a site for sharing and modding designs and synthesis protocols for microfluidic devices, such as the controller/mixer part they use to assemble genetic elements at much smaller scale than pipetting would allow. It’s halfway between Github and Thingiverse, and aimed specifically at shrinking and democratizing the hardware required for synthetic biology. Summary in MIT News.

Build More Biohackers!

  • An article in Nature Biotech argues for increased high school participation in iGEM, and tracks the growth of and lessons learned from Canadian high school iGEM teams. and similar competitions (BIOMOD? BioTreks? News to me).

Who Needs Cells?

Biomolecule Engineering

  • Another tour-de-force Baker lab collaboration: Strauch et al. designed a protein inhibitor of influenza that matches both the geometry and the binding pockets in hemagglutinin, and which can protect mice from influenza the day before or after exposure. Summary in Science.
  • Northwestern alert! Alam et al. design a split fluorescent RNA aptamer that lights up in cells expressing both halves of the aptamer, and can be tagged onto other RNA sequences.

Genetic Circuits

Computational Biology

  • Want to build genomes from scratch, but not a programmer? Then Genome Partitioner, a new web tool from Christen et al. for breaking huge DNA constructs into synthesizable chunks, might be right for you.
  • Want to massively engineer existing genomes? Try Millstone, a web-based toolset from Goodman et al. for designing MAGE experiments in any microbe with a reference genome.
  • Design and build (highly symmetric) biomolecules from scratch with ISAMBARD! Nice open source tool from Wood et al.

CRISPR and Gene Editing

  • Pineda et al. have a very useful review of the challenges facing CRISPR gene editing therapies, and the approaches to solve them.

The Strains, They Are A-Changin’

Metabolic Engineering

Useful Parts Galore

  • Rapidly explore vast genetic design spaces with Woodruff et al.’s new Registry in a Tube: a strategy to make giant pools of standard, barcoded genetic parts, which can then be rapidly extracted and combinatorially assembled into an enormous number of composite devices.
  • What if you want to assemble all your parts-in-a-tube, but don’t want to buy restriction enzymes or Gibson master mix? Liang et al. have a solution: a twin-primer assembly method that requires only DNA primers (with overhangs) and polymerase for PCR.
  • Did you know gut fungi digest lignocellulose using massive complexes of carbohydrate binding and degrading enzymes called cellulosomes? I didn’t. But now Haitjema et al. have figured out a minimal set of genes for scaffolding and assembling fungal cellulosome enzymes. Watch out, cellulosic biomass!

GeneMods has a podcast now!

Excited to announce that the first episode of the GeneMods podcast, Synbio in Spaaaace!, is now live! Jordan Harrison and I interviewed Professor Danielle Tullman-Ercek about synthetic biology in space. We also run through some of the May newsreel, gameshow-style. Hope you all like it!

We’re just starting this thing so we’d love to know what you liked, things you’d change, or topics you want us to explore in future episodes. If you have feedback, you can reach us here or on the GeneMods Twitter account. Looking forward to hearing from you!

SynBio Newsreel, May 2017

 Want to write about synbio?

  • There are three online publications (that I know of) that cater specifically to essays/articles about synthetic biology/biohacking: BioCoder, the PLOS Synthetic Biology blog, and the GeneMods blog. BioCoder has an open call for submissions to its June newsletter, while PLOS SynBio and GeneMods welcome guest writers.

The Means of Production

  • How do you turn more people into scientists? Make it cheaper to do science. How do you make it cheaper to do science? Teach people to build their own equipment. An excellent essay on The Conversation analyzes the intersection of citizen science and the Open Hardware movement, which seeks to develop free manuals for cheaply building all sorts of useful (often scientific) equipment. I particularly liked how the essay argued that making instruments cheaper changes the kinds of experiments people can conduct—science becomes something that can be performed by and for the specific benefit of small, local communities.

Blogs and Community News

Policy and Bioethics

  • GP-Write organized its second annual meeting. They’ve shifted away from immediately synthesizing a human genome, broadening the focus to large genomes generally. Funding remains a challenge, but one pilot project to synthesize a prototrophic human cell has received a $500,000 DARPA grant.
  • The FDA is seeking advice on how to regulate genome editing technologies, and has extended the public comment period through June 19. So if you have any valuable input (when, if ever, might genome edited plants/animals be riskier than those bred or engineered with older techniques? At what point does a small-time bioentrepreneur hacking a new plant/animal need to seek regulatory approval? Can they avoid oversight by using certain biosafety precautions or accepted model organisms?), let the FDA know!

Industry and Funding

  • I think this extended 2012 article about the rise and fall of Amyris is essential reading for anyone interested in the synbio industry. Many things to learn from the successes and mistakes of the first generation of synbio companies.
  • Hey, Open Hardware again! The open source liquid handler OpenTrons gets an upgrade: it can now do everything two times faster. Gotta get one of these for Northwestern!
  • The Economist publishes an enthusiastic essay about cell-free bioengineering. Worth a read to get a sense of all the companies operating in this space!
  • RebelBio, Ireland’s biotech accelerator, has launched its fourth class of startups, including an STD biosensor, a cell-free synbio kit, and microbial fuel cell that runs on wastewater.
  • DNA sequencing is coming to the classroom, courtesy of PlayDNA, a new startup that uses Oxford Nanopore’s MinION sequencer to teach middle schoolers about biology.

Books, Videos, Podcasts

  • Jennifer Doudna is (co-) writing a CRISPR book! Actually, she already wrote it, and it’s coming out in a month or so. The Curious Wavefunction offers an enthusiastic review and synopsis of the book, A Crack in Creation.
  • I just read (well, listened to) Life at the Speed of Light, by J. Craig Venter. It’s a short book packed with Venter’s thought-provoking perspectives about the nature of biology, the history of the life sciences, the Human Genome Project and his transition to synthetic genomics. It also provides entertaining insights into Venter’s personality—namely, that he’s a little obsessed with Nobel prizes, and isn’t above using his book to settle decades-old scores with doubters, competitors and the press.

 

Now, on to the research papers!

The Digital to Biological Converter

  • It’s finally happened: a team led by J. Craig Venter and Dan Gibson have built a digital to biological converter (DBC): a machine which, when fed a digital gene sequence (up to 6000 bases), will print, assemble, and express that gene sequence, all without a human touching it. They use their DBC to make GFP, antibody fragments, and influenza proteins for potential use in vaccine development. This is the first prototype and it’s bulky and expensive, but expect smaller, cheaper DBCs to start showing up in the coming years. This may be the beginning of the end for cloning DNA by hand.

Biomolecule Engineering

Genetic Circuits

Computational Biology

CRISPR and Gene Editing

  • NgAgo? Uh oh. Nature Biotechnology notes that no one can replicate 2016’s DNA-guided gene editing paper.
  • Harrington et al. in Doudna lab report a thermostable Cas9 with increased stability in human serum.

Therapeutic SynBio

The Strains, They Are A-Changin’

Not synbio, but cool

  • Olivia Judson developed an eloquent model of how life got better at exploiting energy over time. This is not technically synbio, but it’s very useful for thinking about how efficiently different organisms can grow/exploit energy.

Pore’s Law

  • Oxford Nanopore’s annual DNA sequencing conference, London Calling, was amazing. Nanopore sequencing is getting faster, cheaper, smaller, larger, more accurate, and higher throughput all at once. Other sequencing companies had better look out. If you want to quickly catch up on everything presented, James Hadfield of Enseqlopedia covered both Day 1 and Day 2 of the conference extensively. Keith Robison over at OmicsOmics had probably the most comprehensive summary and perspective on Clive Brown’s keynote about Oxford Nanopore’s progress and future plans.
  • My favorite nanopore sequencing preprint thus far: Jain et al. report the sequencing and de novo assembly of a human reference genome using only MinION nanopore sequencers. Best part: they tried sequencing extra-long DNA fragments and out popped an 885 kb single read—~1000 times longer than the best read you could get from Sanger sequencing.
  • If you want to really get in the weeds and understand how Oxford’s Nanopore sequencer works, this review on BioRxiv is worth a read.

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