The November meeting’s main event was a presentation and discussion led by Quentin Dudley about the merits of photosynthetic cyanobacteria as a platform for synthetic biology applications. Watch the video below!
Lots of news this month. We’ll post a link to the video version of the newsreel later this week. Enjoy!
Synbio community news
- NASA sequences DNA, in space! They’re up to 1 billion bases and counting. Oxford Nanopore is awesome as always.
- DIY Bio labs all over the world are trying to print biomaterials. This article in Makezine is a good summary of their progress.
- Dominic Berry wrote a guest post on PLOS SynBio about studying the evolution of the synthetic biology community. From it, I learned about Engineering Life, a sociological study of synthetic biology labs in the UK, which runs an absolutely fascinating blog about historian’s perspectives on synbio research and policy.
- GEN surveys the protein engineering field, highlighting recent successes in computational design and directed evolution.
- NSF announces $24 million plan to build a “blue sky” bioengineering center at UCSF.
- The White House announces a major update to how biotechnology is regulated, the first such update since 1992. SynBioBeta has the summary.
- DARPA announces an initiative to develop tools for preventing or reversing gene editing. Digital Rights Management for the genome?
- Most Floridians want to use sterile GM mosquitos to combat Zika. Certainly better than South Carolina’s response.
- Ecologists in Hawaii want to use sterile mosquitos (and are open to deploying gene drives) to protect native bird species from the avian malaria that is wiping them out. Now, Kevin Esvelt and others debate whether and how to use gene drives to protect endangered species at the International Union for the Conservation of Nature.
- NIH announces $20 million in prizes for groups that develop rapid diagnostics of antibiotic-resistant infections.
- Informative review on Motherboard of the history of bioweapons development/use/policy, and of contemporary bioerror (not terror) near-misses. Aaron Dy correctly points out, however, that while the article uses this historical review to discuss the threat of genetically modified bioweapons, all of the past cases involved unmodified pathogens.
- Oxford Nanopore settles Illumina’s lawsuit over protein nanopore patents.
- Ginkgo Bioworks announces partnership with Arthur Daniels Midland, the Chicago-based food conglomerate.
- Monsanto licenses CRISPR from the Broad Institute—but is forbidden from using it for gene drives.
- Nice profile of Ginkgo Biosciences and its history in MIT News.
- The judges in biotech patent cases generally aren’t scientists. The Wall Street Journal proposes a separate patent court staffed by scientific experts to remedy this.
- 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.
- SynbiCITE, the UK’s synbio industry organization, produces Nature Knows Best, a 24 minute documentary about industrial synbio applications in the UK. Enjoyed the Hall of the Mountain King soundtrack!
- Jennifer Doudna sits down with Dan Rather for a 40 minute conversation on CRISPR and her own backstory, filmed by iBiology.
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!
- Howarth lab generates more stable proteins by making them circular, ligating the N and C terminus using their SpyTag-SpyCatcher system.
- Mishler and Barrick labs develop a fast, cheap platform for evaluating non-standard amino acid incorporation using fluorescent proteins in recoded E. coli. Hopefully this will lead to improved synthetic tRNA/tRNA synthetase pairs!
- Baker lab is really on a roll! This month they accurately design small, stable, constrained peptides (similar to the peptides in snake/scorpion venom). They can incorporate D-amino acids and cyclic peptides, too. Summary of the research article here.
- The Coming Age of de-novo Protein Design is a review of advances in, well, you know.
- Simmel lab debuts a rationally designed transmembrane channel made of DNA.
- Pollard lab makes TALE construction easier with a Gibson Assembly-based protocol.
- Chang lab develops a genetic circuit which decouples E. coli growth from production of desired metabolite, leading to higher growth and yields.
- Selling lab builds a bistable genetic circuit using a Lactose/IPTG importer under control of a Lac repressor.
- Bhatia lab at MIT controls CRISPR with light, by chemically sequestering the guide RNAs until UV light shines on them. There’s also a summary in MIT News.
- Fairly comprehensive review of synthetic biology opportunities in plant 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
- Powering enzymatic nitrogen fixation using light and cadmium sulfide nanorods? Pretty cool. Legume Laboratory has a summary article.
- Bibby lab rewires cyanobacterial photosynthesis to increase efficiency and degrade a pesticide. EurekAlert has the summary.
- Collins lab shows that their freeze-dried, cell-free (FD-CF) paper platform can produce vaccine antigens, antimicrobial peptides and even small molecule therapeutics.
- Huang lab builds Salmonella strain which accumulates in tumors and secretes angiogenic inhibitor proteins.
- Quick mini-review of the ways synthetic biology is being used to diagnose disease.
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.
We have more of a newsletter than a newsreel this month, since there’s no summary video. However, that was because we devoted our entire monthly meeting to a thought-provoking critique and discussion of the Human Genome Project-Write, led by Professor Laurie Zoloth. With that said, enjoy the newsreeletter!
Synbio community news:
- Steven Burgess steps down as managing editor at the PLOS SynBio Community. His parting review is typically excellent.
- Great piece on Oxitec’s sterile mosquitos, and the human challenge of testing them in Key West.
- NIH reconsiders its moratorium on human-animal chimera research.
- A PBS article on using CRISPR in grapes turns into a remarkably comprehensive overview of the opportunities and challenges in editing agricultural plants.
- Is NgAgo’s gene editing reproducible? Jury’s still out, but preliminary evidence isn’t good.
- DARPA launches an Engineered Living Materials initiative, with the goal of designing biomaterials that grow into the shape of whatever structure/component. Open for proposals through September!
- Interesting warning about over-hyping technology: a piece on embryonic stem cells and the challenges of treating disease with them.
- If you’re in New York and want to build stuff with bio, you can now take a crash course in making custom biomaterials, put on by New York’s Genspace DIYbio lab.
- If you find yourself in Cambridge, check out Cafe Synthetique, the local synbio salon. Sounds like a GeneMods sister organization!
- Cool profile in STAT of David Baker and co.’s plans to solve problems in the world (mostly diseases, in this piece) with computationally designed proteins.
- Highlights from the 2016 BioDesign Challenge (from last month, but good enough to post anyway).
- Engineered Cas9 with lower off-target effects goes commercial: high-fidelity Cas9 variant from Joung Lab licensed to Editas.
- Total cost of CRISPR patent fight exceeds $20 million and counting.
- DOD gives Ginkgo $2 million to develop probiotic vaccine for traveler’s diarrhea.
Books and Longreads
- I just discovered BioCoder, a quarterly newsletter about synthetic biology from technology media company O’Reilly Media, and I’m really enjoying it.
- Carl Zimmer gets his genome sequenced and analyzed by some of the best researchers in the field. A Game of Genomes chronicles his adventure. A must-read.
- Ed Yong’s fantastic book about the microbes that precede, surround, live on, and comprise us, I Contain Multitudes, came out. I cannot recommend enough that you get your hands (or ears, it’s on Audible!) on this book.
Now, onto the research papers!
- Easily and quickly sensing the presence of small molecules is one of the rate-limiting challenges in metabolic engineering. Now, Savage Lab reports rapid construction of metabolite biosensors using domain insertion profiling.
- Baker Lab does it again, reporting rationally designed, two-component, 120 subunit, icosahedral protein complexes.
- Electrochemical gradients across membranes fundamentally underly pretty much all biological energy production. Fotiadis Lab has now engineered a photo-switchable, light-driven proton pump.
- A Lu Lab collaboration programs yeast and builds a mini bioreactor to produce single doses of multiple biological therapeutics on command.
- A Joung Lab collaboration relaxes Staphylococcus aureus Cas9’s PAM specificity, expanding the sites this smaller programmable nuclease can target.
- It’s been a bumper crop month for making molecular recordings in the genomes of cells. Science published three papers (summarized here): Church Lab reported molecular recordings produced using the actual CRISPR parts of CRISPR (as opposed to Cas9); Lu Lab used recombinases to build state machines in living cells; and a collaboration between Shendure and Schier Labs used Cas9 to record the differentiation and trace the lineage of all the cells in a zebrafish. Then, Lu Lab developed a method to continuously record the presence of Cas9 in human cells using a self-targeting guide RNA.
- Jewett Lab takes a step toward easier natural product mining by expressing non-ribosomal peptide synthetases and producing small-molecule peptides in a cell-free lysate system.
Building biology to understand it
- A massively recoded, 57-codon E. coli? Not quite yet, but Church Lab computationally designs the genome, synthesizes all the parts, and makes progress assembling and testing them.
- Venter Institute edits and interrogates bacterial ribosome genes, on a synthetic bacterial genome in yeast. GenomeWeb has a nice summary if you don’t have time to read the whole paper.
- Review article in ACS SynBio argues that mammalian artificial chromosomes (MACs) are the way of the future.
There was a lot of news this month. Enjoy!
- The Communicating Science Convention (ComSciCon) in Chicago is coming up! If you’re in Chicago on Saturday August 6, I highly recommend you attend the keynote, where Emily Graslie will talk about how she and her team at the Field Museum engage with the public about science online.
- Ellington lab engineers a proof-reading reverse transcriptase. This is awesome.
- Baker lab designs a super-stable 60-subunit protein icosahedron, with optional 60 to 120 GFP attached.
- Precise optogenetic control of gene expression in E. coli enabled by an engineered blue-light-dependent DNA binding protein.
- How do you improve photosynthesis? A review. Reminds me of this talk about plans to convert plants from C3 to C4 photosynthesis.
- Interesting paper on “smart” growth media systems with delayed-release nutrients, and simpler high-yield protein expression protocols.
- Control theory meets synthetic biology: an excellent and rigorous review on designing biological circuits which perform more robustly/predictably.
- Gene expression gets noisier/more stochastic in crowded macromolecular environments. Good thing to keep in mind when, say, prototyping genetic circuits with a dilute cell-free platform.
- Keasling lab engineers new acid-inducible promoters in yeast. 10-fold induction, and they get 10-fold higher production of lactic acid from them.
- Want to tune gene expression? Stick two promoters next to each other and start tweaking. Key phrase: RNA polymerase collision.
- In applied circuit news: Engineered Salmonella grow and explode in cyclic waves within tumors, increase survival in mouse cancer models. This paper also got a write-up in The Atlantic from my favorite science writer, Ed Yong.
- An integral feedback circuit, modeled and implemented in DNA.
- Rewiring native riboswitches to recognize new molecules. If you want to make new riboswitches, this article is a good place to start.
- Battle of the rationally designed transcriptional regulators: which performs better, dCas9 or TALEs? TALEs, as it turns out.
- Daisy chain gene drives proposed, which would only propagate a short. Esvelt also wrote a piece on Medium about daisy drives, informing the public about the idea.
- Cpf1 is more specific than Cas9, as determined by off-target cleavage tests in cells.
- A new biobrick assembly standard which uses Cpf1 digestion. Con: less efficient. Pro: don’t have to worry about restriction sites in your parts anymore.
- Church lab sequences and start building tools to engineer Vibrio natriegens, a saltwater bacterium that grows ~twice as fast as E. coli. Includes CRISPRi system for studying genes’ function.
- BioPartsDB: software that helps you design and build your own large DNA sequences from overlapping oligos.
- ATLAS of Biochemistry: an online map of all known and predicted metabolites, and all known and predicted enzymatic pathways to produce them.
Building biology to understand it
- Yeast engineered to be “multicellular” provide insight into the reason for the distinction between clonally reproducing germ cells and differentiated, non-dividing somatic cells.
- Synthorx gets $10 million Series B financing to expand the genetic code.
- CRISPR Therapeutics raises additional $38 million, bringing their total Series B financing to ~$140 million.
- AI Biosciences adapts a cheap 3D printer into a combination sample handler/ thermocycler.
- Microsoft and UW Seattle partner with Twist to store 200 MB of data, including an OK Go music video, in DNA.
Synbio community news:
- PLOS SynBio Community and EBRC’s Engineering Biology Times are great sources for synbio news.
- “Building with Biology:” reflections on SynBio outreach by Aaron Dy.
- Big picture post on why plant/photoautotroph synthetic biology matters. But, plant synbio isn’t easy. Remember glowing plant? 3 years on, it hasn’t delivered to its Kickstarter backers. MIT Technology Review discusses why.
- NSF awards a $300,000 grant for UPenn to develop synbio classes for high school students. It’s part of the NSF’s initiative to facilitate DIY technology.
- Slightly less controversial “Heroes of CRISPR” piece, about the grad students and post-docs who did the actual experiments.
- Chinese scientists to run first human CRISPR trial next month—a cancer immunotherapy treatment using Cas9-modified cells.
- Not to be outdone, American researchers at UPenn apply for a similar CRISPR cancer immunotherapy trial.
- De-extinction…while a species is still alive? How re-introducing dead alleles could help the black footed ferret.
- Nasa prepares for its first sequencing experiment in space. Oxford Nanopore is awesome.
Cool iGEM projects
- CosmoCrops—Co-culture cyanobacteria and B. subtilis. Cyanobacteria makes sugar, B. subtilis uses sugar to make other things (University of Copenhagen).
- Purdue iGEM team proposes to sequester phosphorus from wastewater and grow nano-wires in E. coli, and raises $3000 on experiment.com to do it.
- Our very own Northwestern iGEM team is tackling the non-viral delivery of Cas9 into bacteria by packaging into Outer Membrane Vesicles (OMVs).
Here are all the links from the May meeting’s newsreel. Enjoy!
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.
5. De novo design of protein structures which associate via hydrogen bond networks (as opposed to hydrophobic effects).
8. Moss assembles DNA in vivo (like yeast!).
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!
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:
- Synthetic biology: what should we be vibrating about? – Drew Endy. (2014)
- Future Biology – J. Craig Venter. (2011)
- The Future of Human Genomics and Synthetic Biology – George Church. (2014)
- Introduction to Synthetic Biology and Metabolic Engineering – Kristala Prather. (2014)
- Programming Living Bacteria – Christopher Voigt. (2016)
- Synthetic Biology: From Parts to Modules to Therapeutic Systems – Ron Weiss. (2015)
2. For more in-depth background training in cell/molecular biology:
- OpenWetWare (which is also a fantastic source for molecular biology protocols and synthetic biology labs) hosts links to a bunch of open online courses in basic cell biology, biochemistry, and genetics, and a whole page devoted to open online synthetic biology courses.
- EdX has a series of excellent open courses on molecular bio, computational/quantitative bio, synbio, and biological manufacturing.
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:
- Foundations for engineering biology. (2005)
- Build life to understand it. (2010)
- Synthetic biology: applications come of age. (2010)
- A brief history of synthetic biology. (2014)
- Integrating biological redesign: where synthetic biology came from and where it needs to go. (2014)
- The new frontier of genome engineering with CRISPR-Cas9. (2014)
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:
- Mike Jewett
- Josh Leonard
- Keith Tyo
- Neda Bagheri
- Milan Mrksich
- Danielle Tullman-Ercek (starting 07/2016)
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:
- Nature Biotechnology
- ACS Synthetic Biology
- Frontiers in Bioengineering and Biotechnology
- Systems and Synthetic Biology
- Metabolic Engineering (focused on one particular sub/twin field, obviously)
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!
If you’re reading this, you’re probably quite interested in synthetic biology. The synbio community is diverse and widely distributed, and I have yet to find a single site which efficiently aggregates all the content that a synthetic biologist might want to read. We started GeneMods in part to pool our collective eyeballs and better keep abreast of developments in synbio research, policy and industry. In that spirit, here is the first post in a series about where to find synthetic biology content on the web.
Automated Search is Your Friend
If you’re lazy like me, the quickest and most powerful way to find articles on synthetic biology is to let your computer do the searching for you. Automated searches save you a bunch of googling, and bring news sources you might never have otherwise discovered right into your email inbox. I recommend using an automated PubMed search to find research articles, and a weekly Google Alert to find both synbio news and the sites that publish it.
Automated PubMed Search
This is a really easy and flexible way to get a ton of primary literature. It takes literally five steps:
- Register for a PubMed/NCBI account. All it takes is an email address, username and password.
- Go to PubMed, and search “synthetic biology” (include the quotes) while signed in on your account.
- Click the “Create alert” button right under the search bar.
- Adjust the number/frequency/date settings to your liking. I set mine to email me the abstracts and links to 10 synbio articles every Saturday morning. Yay weekend reading!
- Save your settings, and adjust them later by clicking the “My NCBI” button at top right and editing your Saved Searches.
If all goes well, you should start receiving emails from “My NCBI” which summarize recently published synthetic biology research.
Google is pretty good at finding stuff, and Google Alerts are a simple way to have Google bring that stuff to your inbox. I particularly like Google Alerts because they show me articles from sites I wouldn’t have otherwise found, some of which have since become my favorite sources of synbio news and essays. Setting up a Google Alert also takes only five steps:
- Sign into your Google/Gmail account.
- Go to google.com/alerts.
- Type “synthetic biology” into the search bar.
- Click “Show options” and adjust the number/frequency/language settings to your liking. I set mine to receive the best results in English from any region once a week.
- Save your Alert, and adjust them later by going back to google.com/alerts.
You should start receiving emails from Google Alerts containing titles, links and the first few lines of synbio news articles from around the web.
There’s a Whole World Out There!
I’ve outlined two simple and useful automated searches, but these are by no means the only or the best ways to find synbio content online. I like to think of them as starting points: with these searches, you can start to figure out which journals and labs publish the papers you like, and which sites publish articles you enjoy reading. From there, you can subscribe to weekly newsletters or RSS feeds for the sites you really like, set up further PubMed searches to flag articles from your favorite lab or sub-field, and google your favorite authors to find their blogs. In future posts I’ll outline some of the best sources of synbio content I’ve found through these further searches. In the meantime, I hope I’ve made it a little easier to explore the world of synthetic biology.
Special thanks to Drew Endy for first showing me how to set these searches up.