This Week in Synthetic Biology #2

Engineered T-cells controlled with ultrasound, genetic circuits designed for yeast, a chemically-controlled gene drive, and more.

Good morning. This week…

Undark considered how gene editing could make meatier cows, STAT hosted a virtual CRISPR event with Alexis Thompson and David Liu, Massive Science drew parallels between cultivated meat and Tesla Roadsters, and researchers at the University of New England sexed chickens from feather DNA.

Meanwhile, an article in The Ecologist mentioned that the UK government is “considering the deregulation of genome-edited organisms in agriculture”. A press release from the University of Oregon highlighted the new Plesa lab and DropSynth 2.0, WIRED published a “CRISPR guide,” and Axios spoke with Jennifer Doudna about CRISPR and coronavirus diagnostics.

In industry news, Carisma can proceed with a Phase 1 trial after all-clear for engineered macrophage immunotherapy, Ginkgo announced their 2020 creative residents, and Genetic Engineering & Biotechnology News published a piece on companies using base editors, exonucleases, and other gene-editing tools.

In coronavirus testing news, UC Davis scientists received a $1.2M NIH grant to “create mice that are susceptible to the COVID-19 virus,” Oxford Nanopore launched LamPORE, and Ginkgo, Mammoth, and others were among winners of $250M NIH award to scale up COVID-19 testing.

This week in research…

Controlling Engineered T-cells with Ultrasound

In the latest work from the Shapiro lab at Caltech, published in ACS Synthetic Biology, T-cells with engineered heat shock promoters were controlled “with brief pulses of heat delivered by focused ultrasound,” inducing them to release cytokines and target tumor cells.

Automated Genetic Circuit Design for Yeast

At MIT, the Voigt lab has constructed nine NOT/NOR gates, with a 400-fold dynamic range, in S. cerevisiae. With these gates in hand, they then used Cello 2.0, a software to design genetic circuits, to “build circuits with up to 11 regulatory proteins.” The study could dramatically simplify circuit design for eukaryotic synthetic biology, and was published in Nature Microbiology.

Automated Cell Culture System with DIY Hardware (Open Access)

With some printed circuit boards and off-the-shelf components, costing about $300, a team at Oxford has created a cell culture automation system with several useful features; the device can measure and record cell growth, and the seven-color LEDs can be used to measure multiple fluorescent proteins in parallel, or for optogenetics. The system, called Chi.Bio, was published in PLoS Biology.

For more on this study, check out my interview with the lead author, Dr. Harrison Steel.

Phase Separation in Human Cells with “Designer” Disordered Proteins

The Chilkoti lab at Duke University has designed a set of artificial, intrinsically disordered proteins (IDPs) that can be used to engineer intracellular condensates in living cells. In a new study, published in Nature Chemistry, they show that the behavior of the engineered condensates are predictable, and can be tuned by controlling the mass and structure of the IDPs. Chilkoti said in a Duke press release that this study “provides very simple engineering principles to program this behavior [intracellular condensates] within a cell.”

Chemicals Stymie CRISPR Gene Drives

At Yonsei University, in Seoul, South Korea, the Kim lab has developed a chemical method to control CRISPR-based gene drives in Drosophila fruit flies. Using a site-specific recombinase induced by a chemical, called RU486, they demonstrate a gene drive removal rate of 7-12% in each generation. The work was published in ACS Synthetic Biology.

More research…

A bimodular PKS platform that expands the biological design space by Zargar, A. et al. in Metabolic Engineering.

A microgravity responsive synthetic genetic device in Escherichia coli by Mukhopadhyay, S. and Bagh, S. in Biosensors and Bioelectronics.

A novel strategy for creating a new system of third‐generation hybrid rice technology using a cytoplasmic sterility gene and a genic male‐sterile gene by Song, S. et al. in Plant Biotechnology Journal. (Open Access)

A protein-independent fluorescent RNA aptamer reporter system for plant genetic engineering by Bai, J. et al. in Nature Communications. (Open Access)

Bidirectional titration of yeast gene expression using a pooled CRISPR guide RNA approach by Bowman, E.K. et al. in PNAS.

CRISPR-assisted multiplex base editing system in Pseudomonas putida KT2440 by Sun, J. et al. in Frontiers in Bioengineering and Biotechnology. (Open Access)

Display of lead-binding proteins on Escherichia coli surface for lead bioremediation by Jia, X., Li, Y., Xu, T. and Wu, K. in Biotechnology and Bioengineering.

DNA targeting and interference by a bacterial Argonaute nuclease by Kuzmenko, A. et al. in Nature.

Engineering Escherichia coli towards de novo production of gatekeeper (2S)-flavanones: naringenin, pinocembrin, eriodictyol and homoeriodictyol by Dunstan, M.S. et al. in Synthetic Biology. (Open Access)

Engineering the carotenoid biosynthetic pathway in Rhodothermus marinus for lycopene production by Kristjansdottir, T. et al. in Metabolic Engineering Communications. (Open Access)

Integrated pipeline for the accelerated discovery of antiviral antibody therapeutics by Gilchuk, P. et al. in Nature Biomedical Engineering. (Open Access)

Mixing and matching methylotrophic enzymes to design a novel methanol utilization pathway in E. coli by De Simone, A. et al. in Metabolic Engineering.

Multiplexed optical sensors in arrayed islands of cells for multimodal recordings of cellular physiology by Werley, C.A. et al. in Nature Communications. (Open Access)

Noise suppression by stochastic delays in negatively autoregulated gene expression by Smith, M. and Singh, A. Abstract for the 2020 American Control Conference.

Rapid method for generating designer algal mitochondrial genomes by Cochrane, R.R. et al. in Algal Research.

Rational design and implementation of a chemically inducible heterotrimerization system by Wu, H.D. et al. in Nature Methods.

Rational discovery of molecular glue degraders via scalable chemical profiling by Mayor-Ruiz, C. et al. in Nature Chemical Biology. For more, read the News & Views piece on this article.

Scarcity of cellular resources decreases the robustness of toggle switches to noise by Gyorgy, A. Abstract for the 2020 American Control Conference.

Tailoring cyanobacteria as a new platform for highly efficient synthesis of astaxanthin by Diao, J. et al. in Metabolic Engineering.

The Synthetic Biology Open Language (SBOL) Version 3: Simplified data exchange for bioengineering by McLaughlin, J.A. et al. in Frontiers in Bioengineering and Biotechnology.

This week in reviews…

Advances on systems metabolic engineering of Bacillus subtilis as a chassis cell by Xiang, M., Kang, Q. and Zhang, D. in Synthetic and Systems Biotechnology. (Open Access)

Bacterial cellulose: From production optimization to new applications by Fernandes, I.A.A. et al. in Macromolecules.

Harnessing cells to deliver nanoparticle drugs to treat cancer by Singh, B. and Mitragotri, S. in Biotechnology Advances.

Production of plant natural products through engineered Yarrowia lipolytica by Muhammad, A. et al. in Biotechnology Advances.

Sequencing enabling design and learning in synthetic biology by Gilliot, P. and Gorochowski, T.E. in Current Opinion in Chemical Biology.

This week in preprints…

A MATLAB toolbox for modeling genetic circuits in cell-free systems by Singhal, V. et al. bioRxiv.

An efficient vector-based CRISPR/Cas9 system in an Oreochromis mossambicus cell line using endogenous promoters by Hamar, J.C. and Kültz D. bioRxiv.

A novel prokaryotic CRISPR-Cas12a based tool for programmable transcriptional activation and repression by Schilling, C., Koffas, M.A., Sieber, V. and Schmid, J. bioRxiv.

Base-edited CAR T cells for combinational therapy against T cell malignancies by Georgiadis, C. et al. bioRxiv.

BioCRNpyler: Compiling chemical reaction networks from biomolecular parts in diverse contexts by Poole, W. et al. bioRxiv.

Cheetah: a computational toolkit for cybergenetic control by Pedone, E. et al. bioRxiv.

CRISPR interference as low burden logic inverters in synthetic circuits: characterization and tuning by Bellato, M. et al. bioRxiv.

CRISPR Turbo Accelerated Knock Out (CRISPy TAKO) for rapid in vivo screening of gene function by Plasil, S.L., Seth, A. and Homanics, G.E. bioRxiv.

De novo design of picomolar SARS-CoV-2 miniprotein inhibitors by Cao, L. et al. bioRxiv.

Distinguishing critical, beneficial, neutral and harmful mutations uncovered in the directed evolution of a yeast membrane receptor by Adeniran, A. and Tyo, K.E.J. bioRxiv.

Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi by Adolfi, A. et al. bioRxiv.

Engineered ACE2 receptor traps potently neutralize SARS-CoV-2 by Glasgow, A. et al. bioRxiv.

Generative probabilistic biological sequence models that account for mutational variability by Weinstein, E.N. and Marks, D.S. bioRxiv.

Genetically-encoded fluorescent biosensor for rapid detection of protein expression by Eason, M.G. et al. bioRxiv.

MASSpy: Building, simulating, and visualizing dynamic biological models in Python using mass action kinetics by Haiman, Z.B. et al. bioRxiv.

Minicells as a potential chassis for engineering lineage-agnostic organisms by Wei, E., Jackson-Smith, A. and Endy, D. bioRxiv.

Precise genome engineering in Drosophila using prime editing by Bosch, J.A., Birchak, G. and Perrimon, N. bioRxiv.

Predator: A novel method for targeted protein degradation by Liu, C. et al. bioRxiv.

SARS-CoV-2 detection with de novo designed synthetic riboregulators by Koksaldi, I.C. et al. medRxiv.

Scalable metabolic pathway analysis by Øyås, O. and Stelling, J. bioRxiv.

Swab-Seq: A high-throughput platform for massively scaled up SARS-CoV-2 testing by Bloom, J.S. et al. medRxiv.

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

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