SynBio Newsreel, November

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

Synbio community news

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

Industry news

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

Now, on to the research papers!

Biomolecule engineering

CRISPR/gene editing

SynBio Newsreel, October

Synbio community news

  • So, SynBioBeta (San Francisco) happened. SynBioBeta summarized the achievements and announcements from the synbio industry, while Aaron Dy of PLOS SynBio wrote a typically excellent perspective piece of the broader issues and intellectual currents running through the synbio industry’s largest conference.
  • My favorite science writer, Ed Yong, wrote a piece on the freeze-dried sensing and production systems pioneered by Collins lab. And there’s even a quote from new Northwestern professor Danielle Tullman-Ercek in there!
  • The Department of Energy’s Bioenergy Technologies Office (BETO) announces a $35 million advanced biofoundry centered at Lawrence Livermore National Laboratory.
  • If Elon Musk wants to colonize Mars, he’s going to need biotechnology. The Motley Fool’s Maxx Chatsko explains why.
  • Tobi Ogunnaike at SingularityHub looks ahead to the questions and challenges that face the field of DNA data storage.
  • BBC Horizons devotes an entire show to synthetic biology. Craig Venter, Christina Smolke, Amyris and IndieBio all feature.

Synbio profiles

Industry news

  • Venture capital interest in synbio continues to rapidly grow. Last year, synthetic biology companies raised half a billion dollars, and it looks like that trend is going to continue. Zymergen, the west coast’s answer to Ginkgo Bioworks, raised a $130 million Series B round. (Zymergen also happens to run a really excellent Medium account that links to several in-depth posts about their data-driven approach and vision for synbio). IndieBio announced its 4th class, including companies tackling the antivenin shortage and the cost of high throughput biotech equipmentNew VC firm Fifty Years, founded to fund companies that will help the world meet the UN’s Sustainable Development Goals, is particularly interested in synthetic biology. And buried in this fascinating profile of Y Combinator head Sam Altman is a reference to his plans to build a synthetic biology unit within the research arm of YC.
  • Oxford Nanopore continues to be awesome. Their MinION sequencer is already cool (its current capabilities are summarized nicely here), but it looks like their whole platform will get even more exciting soon. In a technical update (full video here), they announce impressive upgrades in sequencing on the MinION, and a number of truly exciting future projects. Is a gigabase-per-second sequencer possible? Will GATTACA-like portable sequencers soon be everywhere? I wouldn’t bet against it in the next decade.
  • Jason Kelly, CEO of Ginkgo, argues that synbio companies need to both specialize more and collaborate more, rather than trying to do everything in-house. Also, Xconomy tours and profiles Ginkgo, highlighting their recent deals with Amyris and Genomatica.
  • Speaking of Amyris, they and Synthetic Genomics, two of the oldest synbio companies, are pivoting away from biofuels and towards biopharmaceuticals. It’s a smart move given the margins in pharma, but also a sobering acknowledgment that economically competitive and renewable biofuels are a long way off.
  • Egelie et al. comprehensively survey the CRISPR patent landscape, which is quickly starting to look very thicket-y.
  • Startup 20n writes a blog post about how deep learning algorithms can simplify and speed up high-throughput metabolomic analysis and facilitate strain engineering.

Books and Longreads

  • I read (actually, listened to) Siddartha Mukherjee’s The Gene: An Intimate History this month, and I cannot recommend it enough. Mukherjee takes the reader/listener all the way from ancient Greek theories of inheritance, though the discovery of evolution and the rise of eugenics, to the molecular biology and biotech revolutions, to the Human Genome Project and the sequencing revolution, and right up to the current state of the art in gene diagnosis and editing, all while centering the book around his own family’s struggles with mental illness. The best nonfiction book I’ve read since I Contain Multitudes.
  • Springer published a Synthetic DNA protocols book. Highlights include a 6 hour cloning protocol and instructions for de novo gene synthesis and error correction from oligonucleotide arrays. Worth checking out!

Biosecurity

  • In order to prevent secretive/unsafe research on CRISPR gene drives, Kevin Esvelt floats the idea of using his patents to force scientists to publish open plans and protocols for gene drive research. The article also includes a 20 minute talk from Esvelt that summarizes current projects to develop and deploy gene drives to treat diseases in the world.

Now, on to the research papers!

Biomolecule engineering

  • Giessen and Silver turn a phage capsid into a highly stable bacterial microcompartment which concentrates enzymes of interest, is stable for a week at room temperature and increases indigo synthesis in E. coli by 60%.
  • Hartig lab modifies Twister ribozymes into a relatively modular, programmable system for controlling gene expression, developing sensor/switches that activate or repress gene expression in the presence of small molecule inputs in both E. coli and yeast.

Genetic circuits

  • The repressilator gets a major upgrade: by deleting a protein degradation gene and adding binding sites for one of the repressors, Potvin-Trottier et al. make the original repressilator circuit oscillate robustly and synchronously over more than 60 generations.
  • The discovery of new and useful enzymes from genome databases remains one of synbio’s rate limiting challenges. Genee et al. have developed a modular, riboswitch-based system to select importers of specific molecules from a library of uncharacterized bacterial importers.

Cell-free synbio

  • Some familiar names here! Jessica Perez, Jessica Stark and Mike Jewett review the state of the art in cell-free protein synthesis.
  • Krinsky et al. report a method to generate crude cell-free lysate in less than an hour.

CRISPR/gene editing

The strains, they are a changin’

  • Bryn Adams argues in ACS Synthetic Biology that we need new platform organisms beyond the molecular biology models of yesteryear, like E. coli and S. cerevisiae. Adams’s most interesting argument (to me) is that extremophiles are better platforms because their growth conditions can be the only selection marker needed to prevent contamination.

Metabolic engineering

  • Synthesis from CO2 and sunlight (well, actually fluorescent lamps): Woo lab engineers cyanobacteria to produce amorphadiene, a precursor for the antimalarial drug artemisinin.
  • How do you grow giant batches of bioproductive microbes without antibiotics, and avoid culture contamination? Use an extremophile! Chen lab engineers halophilic, alkaliniphilic Halomonas bacterium to produce protein surfactant PhaP. It’s Bryn Adams’s perspective piece in action!
  • Professors from Waginengin University in the Netherlands review the progress and potential of microbial autotrophs to produce useful chemicals. Key point for me: plants are less energetically efficient than cyanobacteria/microalgae, and cyanobacteria/microalgae are less efficient than chemolithoautotrophs hooked up to solar panels and water splitting catalysts. However, energetic efficiency and productivity are very different things.
  • Borkowski et al. argue in a review that the metabolic load of genetic circuits on cells should be as important a design consideration as circuit performance.

Computational biology

  • Northwestern’s own Leonard lab improves quantitative biology by developing a modeling strategy for predicting how DNA replication and gene copy number affect expression from different genome loci under a variety of growth conditions in E. coli.
  • Do you ever find yourself torn between designing your genetic pathway by composition, or by optimization? Do you have no idea what ‘design by composition’ or ‘design by optimization’ are? Well, a new paper from Tanevski et al. could help solve both those problems. They report a way to combine libraries of standardized parts with mathematical models of the desired behavior of a genetic circuit, make a bunch of possible compositions of parts to satisfy the desired behavior, and rank/optimize those compositions.

Tissue engineering

SynBio Newsreel, September

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

Synbio community news

Biosecurity

Industry news

Longreads

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

Video

Non-synbio blog of the month

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

Now, on to the research papers!

Biomolecule engineering

Genetic circuits

CRISPR/gene editing

Metabolic engineering

Building biology to understand it

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

Autotrophs and agriculture

Therapeutic synbio

The strains, they are a changin’

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

SynBio Newsreel, August

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:

Industry news:

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!

Protein engineering:

Genetic circuits:

CRISPR/Gene Editing:

Metabolic Engineering

Building biology to understand it

SynBio Newsreel, July

There was a lot of news this month. Enjoy!

Northwestern News:

  • 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.

Protein engineering:

Genetic circuits:

CRISPR/Gene Editing:

Computational/Bioinformatics

  • 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

Industry news:

Synbio community news:

Cool iGEM projects

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!

Human Genome Project: Write

On May 10th, a group of scientists led by George Church met in a closed-door, invitation only session to discuss the possibility of synthesizing the human genome. The intent was to publish a proposal outlining the need for human genome synthesis. That perspective piece was recently published in Science, and now has its own website. Among the goals and applications for human genome synthesis are:

 

  • To drive demand for large-scale DNA synthesis, and thus lower costs
  • To understand basic biology by re-creating noncoding DNA regions
  • To construct specific genotypes to study disease
  • To construct artificial chromosomes with all-included developmental pathways (minimal human cells, anyone?)
  • For gene therapy applications: improve safety by removing viral and cancer susceptibility, etc.
  • To recoding human cells for safety and biocontainment in manufacturing
  • To create a homozygous “pan-human” reference genome for drug testing

Drew Endy was invited but chose not to attend, instead exposing the meeting to the public and co-authoring an opinion piece on the ethics of human genome synthesis with our own Laurie Zoloth. Concerns raised in their piece include:

  • The secrecy and lack of public dialog severely damage public trust
  • The individuals involved have a financial conflict of interest
  • A non-human model organism genome synthesis project can provide the same demand to fuel low-cost DNA synthesis
  • No ethical analysis has been undertaken
  • A large potential for unintended consequences, especially on funding for the entire field of synthetic biology

What do you think? Join the discussion below!

GeneMods Connect! A networking event

We’re excited to announce our first networking event, GeneMods Connect! This event is intended as a time to socialize with other members of the GeneMods community, share about your research interests, and find potential connections or collaborations. RSVP soon using the form below. Space is limited to 30 participants.

 

Thursday, May 12        5-7pm        Pancoe Cafe

Light dinner provided      Alcoholic beverages provided

 

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!