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.

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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, 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.

April Newsreel (a lot late)

As long as I’m posting the May links, the April links should go up too. Enjoy!

–Isaac

Research articles:

  1. Synthetic mammalian gene circuits
  2. Expanding DNA Polymerase function
  3. Synthetic biochemistry module produces valuable chemicals from glucose
  4. Programming IPSC differentiation with a genetic circuit
  5. Cellular device for liver protection
  6. Rapid and efficient incorporation of long DNA fragments into E. coli genomes
  7. A step towards rational dynamic control of gene expression
  8. Research Highlight: A minimal synthetic cell.
  9. Research highlight: Automated genetic circuit design.

Non-research stuff

  1. ComSciCon is awesome! Chicago meeting’s in August, come to the keynote.
  2. The Foundry (DNA factory) Opens in the UK
  3. Perspective article on biosafety in DIY bio communities
  4. Oxford Nanopore responds to Illumina lawsuit
  5. Tech Museum Synthetic Biology Exhibit
  6. GM Mushroom escapes US Regulations
  7. Sean Parker starts $250 million cancer immunotherapy institute

May Newsreel (a little late)

Here are all the links from the May meeting’s newsreel. Enjoy!

—Isaac

Non-research articles:

1. Gen9 and Arzeda sign DNA synthesis deal. In related news, Twist Bioscience partners with Microsoft on DNA data storage. But how big is the synthetic DNA market? Rob Carlson’s perspective.

2. Synthetic biology tackles the antivenin shortage.

3. DIY bio lab in Brooklyn gets a profile in The Guardian.

Research articles:

4. Modeling competition between genes for expression machinery.

5. De novo design of protein structures which associate via hydrogen bond networks (as opposed to hydrophobic effects).

6. DNA nanostructures encoded and self-assembled in living bacteria.

7. Computationally designed protein enables biomineralization of cadmium chloride nanocrystal.

8. Moss assembles DNA in vivo (like yeast!).

9. Targeted isolation and cloning of 100 kb microbe genome fragments through Cas9-assisted technique.

10. DNA-guided genome editing with Natronobacter gregoryi Argonaute (NgAgo)—comparable in vitro editing to Cas9, but uses guide DNA rather than RNA, and doesn’t require a PAM sequence!

Synthetic Biology Sources: Where to Start

Just after the grand opening of Northwestern’s new Center for Synthetic Biology, I got an email from a research assistant professor with a background in physics who was excited about synbio and wanted to know how to get up to speed on the field. What follows is a modified version of the email I sent him, which comprises most of the resources I’ve found and have used online to learn about synthetic biology. This post is by no means comprehensive (the list of important labs is especially incomplete, and probably merits its own post), but hopefully this is a useful starting point for anyone interested in learning more about the field.

List of Synthetic Biology Resources

1. There are a lot of really excellent presentations on Youtube which provide broad overviews of synthetic biology and background about where the field came from. Here are a few of them, which I’ve tried to arrange from most accessible to most academic/wonky:

2. For more in-depth background training in cell/molecular biology:

3. There are a bunch of excellent review articles for the field that link out to lots of seminal synbio papers. Here are some of them:

4. This special issue of Nature on systems and synthetic biology, while ~5 years old, is filled with important papers and perspectives, both contemporary with its publishing (2010) and reviewing the highlights of the field from 2000-2010. I particularly recommend the News and Views articles in it for a quick summary of where the field has gone and is going.

5. There are several labs whose research I recommend searching for/keeping abreast of, as they are important for various areas of synthetic biology:

  • Michael Elowitz, Caltech
  • Jim Collins, MIT
  • Christopher Voigt, MIT
  • Drew Endy, Stanford
  • Pam Silver, Harvard
  • David Baker, UW Seattle
  • George Church, Harvard
  • Christina Smolke, Stanford
  • Jay Keasling, UC Berkeley
  • Jennifer Doudna, UC Berkeley
  • Feng Zhang, MIT
  • John Dueber, UC Berkeley
  • Martin Fussenegger, ETH Zurich
  • Tom Ellis, Imperial College London
  • Ron Weiss, MIT

Synthetic Biology professors at Northwestern:

6. If you’re interested in learning about the policy/industry/economic aspects of synthetic biology, I recommend Rob Carlson’s book Biology is Technology, a lot of which is available online through that link for free. Carlson is generally a good source of realistic predictions about the field’s future. I also recommend his blog, Synthesis.

7. Speaking of blogs, here are a few other blogs/news sources I’ve found that regularly feature news/commentary about synthetic biology: 

  • PLOS SynBio (a blog completely devoted to synthetic biology/the synbio community)
  • Genome Web (mostly genomics, but lots of stuff on the synthetic biology industry)
  • Holman’s Biotech IP Blog (all about biotech and the law; had an excellent series recently on why DNA should be protected by copyright, not patents)
  • Trade Secrets (Nature’s biotech blog)
  • GetSynBio (good source for companies that provide synthetic biology services)

8. Carlson’s not the only person writing policy pieces on the field. Synberc (the Synthetic Biology Engineering Research Center, one of the first/biggest synbio organizations) maintains a list of white papers which discuss and argue about how the research, commercialization and regulation of synthetic biology should proceed. They make for very interesting reading.

9.  Here are a few journals that regularly publish synthetic biology research:

10. Finally, to keep up with current developments in synthetic biology, I recommend setting an auto-search on PubMed and Google News for synthetic biology. I wrote an article recently about how to do this. I actually think this is a more efficient way to find new research/developments in synthetic biology than reading particular journals.

What did I miss?

I’m planning to update/revise this post as new and better resources come to my attention. If you think I left something obvious off, let me know in the comments!