This Week in Synthetic Biology #1

A self-healing biomaterial from squid, base editor structure solved, and more!

Good morning.

A growing number of companies and laboratories are implementing genetic engineering (via CRISPR and other means) into their work, leading to an explosion of publications and news articles on the field.

In academic news, researchers at UCLA and UCSB received a $23.7 million grant from the NSF to study biologically based polymers. Meanwhile, the founder and CEO of Faber Futures, a biodesign lab, talked about fashion, synthetic biology, and how clothes can be created using bacteria, in an interview with HIGHSNOBIETY. Grow by Ginkgo published an interview with Jeantine Lunshof about xenobots.

The San Francisco Chroniclewrote about Atum, a Bay Area biotechnology company that pivoted, during the coronavirus pandemic, to help address a need for the manufacturing of synthetic genes and proteins. Another company that makes DNA (albeit using an advanced method), in France, expanded their Series B funding to $89MDNA Script uses enzymes to synthesize DNA, and will soon release a bench-top machine, called a DNA printer, that can literally print DNA on-site, in under a day.

Chemistry World ran a piece about the scientific quest to develop ‘foldamers’, self-folding molecules that could one day be used to develop more targeted therapies and study how RNA and proteins fold in living cells.

Finally, a Scientific American article discussed research on the thousands of hormones found in plants, and how engineers could tweak them to improve crop yield. In OneZero, here on Medium, a new article discussed the cows that have been genetically engineered to produce mostly male offspring.


A slew of peer-reviewed research results were published this week, including a high-resolution of a base editor protein (used for targeted genetic engineering applications) and a machine learning model that can shut down CRISPR in its tracks.

Self-Healing Material Made from Squid Teeth Protein
A joint effort from the Sitti and Demirel labs, of the Max Planck Institute for Intelligent Systems and Penn State University, respectively, have developed a biosynthetic, self-healing material using proteins found in squid teeth. Published in the prestigious journal, Nature Materials¹, the material can heal itself in about one second, far faster than previous self-healing materials used in soft robotics. The study was picked up by several news outlets and organizations, including the U.S. Army and The Times.

Structure of DNA Base Pair Editor, ABE8e, is Resolved
At UC-Berkeley, the Doudna laboratory published a 3.2-angstrom resolution structure of the ABE8e base editor bound to DNA in the journal Science². ABE8e can convert A•T base pairs in the genomes of living cells to G•C, at a rate much faster than previous base editors. This base editing protein was originally created by the Liu lab at Cambridge’s Broad Institute. To read more about the high-resolution ABE8e structure, check out the UC-Berkeley press release.

Anti-CRISPR Proteins Designed Using Machine Learning
The Koonin lab at the National Center for Biotechnology Information (NCBI), in Bethesda, Maryland, used machine learning to design anti-CRISPR proteins, molecules that can inactivate CRISPR-associated proteins, which may have applications in turning off unwanted, genetic edits in living cells. The study was published in Nature Communications³.

A New Tool for Tracing Cellular Lineages
An exciting area of research in synthetic biology in the last few years has been lineage tracing, in which researchers “trace” the genetic ancestry of each cell in an organism. In principle, one could watch a handful of cells develop into a fully-fledged animal, and determine where each of the cells in the fingers, toes, and tongue came from. Now, researchers at the Research Institute of Molecular Pathology, in Vienna, have developed an improved lineage tracing tool, called CaTCH, which uses a modified form of CRISPR to both identify, and isolate, extremely rare cell clones from the millions of cells in a population. The work was published in Nature Biotechnology.

Tracking Gene Levels in Living Cells
group at the University of Pennsylvania developed a method called MemorySeq which uses RNA sequencing to identify “slowly fluctuating gene expression states in rare single cells”. Published in the journal Cell, the method could possibly be used to quantify “non-genetic heritability” of cellular states.

Controlling Neoantigens in Mice; Applications for Studying Cancer
Researchers at Yale and MIT have figured out a way to induce the expression of neoantigens — antigens that have not been previously recognized by a person’s immune system, often from a mutation in a tumor — in living mice. The method, called NINJA, was published in Nature Biotechnology and could help scientists study how T-cells, a type of immune cell, behave during organ transplantation, autoimmune diseases, and cancer.


New preprints, posted on bioRxiv, are provided in abbreviated form.

Domino: reconstructing intercellular signaling dynamics with transcription factor activation in model biomaterial environments by Cherry, C. et al.

Combinatorial CRISPR screening reveals functional buffering in autophagy by Diehl, V. et al.

De novo designed receptor transmembrane domains enhance CAR-T cell cytotoxicity and attenuate cytokine release by Elazar, A. et al.

Testing theoretical minimal genomes using whole-cell models by Rees-Garbutt, J. et al.

Engineering DNA templated nonribosomal peptide synthesis by Huang, H., Stephan, P. and Kries, H.

Mapping the Functional Landscape of the Receptor Binding Domain of T7 Bacteriophage by Deep Mutational Scanning by Huss, P. et al.

Environmental fluctuations reshape an unexpected diversity-disturbance relationship in a microbial community by Mancuso, C.P. et al.

A Wearable Optical Microfibrous Biomaterial with Encapsulated Nanosensors Enables Wireless Monitoring of Oxidative Stress by Safaee, M.M. et al.

Optimized gene expression from bacterial chromosome by high-throughput integration and screening by Saleski, T.E. et al.

The E. coli Cas1/2 endonuclease complex reduces CRISPR/Cascade guide array stability by Ye, Z. et al.


References

  1. Pena-Francesch, A., Jung, H., Demirel, M.C. et al. Biosynthetic self-healing materials for soft machines. Nat. Mater. (2020). https://doi.org/10.1038/s41563-020-0736-2.

  2. Lapinaite, A., Knott, G.J. et al. DNA capture by a CRISPR-Cas9–guided adenine base editor. Science (2020). Vol. 369, Issue 6503, pp. 566–571. https://doi.org/10.1126/science.abb1390

  3. Gussow, A.B., Park, A.E., Borges, A.L. et al. Machine-learning approach expands the repertoire of anti-CRISPR protein families. Nat Commun.11, 3784 (2020). https://doi.org/10.1038/s41467-020-17652-0

  4. Umkehrer, C., Holstein, F., Formenti, L. et al. Isolating live cell clones from barcoded populations using CRISPRa-inducible reporters. Nat Biotechnol (2020). https://doi.org/10.1038/s41587-020-0614-0

  5. Shaffer, S.M., Emert, B.L. et al. Memory Sequencing Reveals Heritable Single-Cell Gene Expression Programs Associated with Distinct Cellular Behaviors. Cell (2020). https://doi.org/10.1016/j.cell.2020.07.003

  6. Damo, M., Fitzgerald, B., Lu, Y. et al. Inducible de novo expression of neoantigens in tumor cells and mice. Nat Biotechnol (2020). https://doi.org/10.1038/s41587-020-0613-1


This Week in Synthetic Biology is published every Friday, and covers the latest peer-reviewed research, preprints, and other news in the field. A version of these newsletters is also posted on Medium and hiniko.io. By Niko McCarty.