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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