DNA with Six Helices, Robots Help COVID-19 Testing & Gene Expression Controlled with Light (#7)

Plus: David Baker receives 2021 Breakthrough Prize, some Cas proteins are more specific than others, and CRISPR diagnoses sick apples.

🧬Featured Research

DNA Double Helix? Nah. Give Me Six!

DNA, the molecular blueprint of life, also moonlights as an origami artist. By carefully choosing a collection of DNA sequences, scientists can coax the strands to bend and fold into complex arrangements at a nanoscopic scale. Lulu Qian, at Caltech, even used DNA origami to create “the world’s smallest Mona Lisa” in 2017. But DNA nanostructures have thus far been limited in scale. A new paper from Hao Yan’s group at Arizona State University has created a “six-helix bundle DNA origami nanostructure”, called meta-DNA, that can be used to construct larger, three-dimensional structures. The work was published in Nature Chemistry. Read the ASU press release.

Apples Get Sick, Too. Can CRISPR Provide the Diagnosis? (Open Access)

China produces nearly half of the world’s apples, which are subjected to an onslaught of viral pathogens. Those viruses have all sorts of fun names, like the “apple stem grooving virus” and the “apple scar skin viroid”. Fending off these viruses, and saving an orchard, demands early detection. That’s why Xianbo Zheng’s lab at Henan Agricultural University developed a CRISPR/Cas12-based system that can detect as few as 250 copies of certain viruses on an apple tree leaf, and return results in less than an hour.

Here’s a riddle for you: If an apple a day keeps the doctor away, what do apples eat to stave off illness?

Using Robots to Automate SARS-CoV-2 Testing (Open Access)

When I studied at Imperial College, my dream was to use the Biofoundry. A full room, humming with robots, was surely the cure for my monotonous experiments. But, alas, it has been put to better use. In a Nature Communications article out this week, Paul Freemont’s group reports a “reagent-agnostic automated SARS-CoV-2 testing platform”. In other words, the Biofoundry was used to perform RNA extractions, RT-qPCR, and CRISPR-based detection methods for the virus. It was even tested on patient samples, installed in NHS diagnostic centers, and will purportedly increase “testing capacity by 1000 samples per day”.

Massive CRISPR Experiment Proves Not All Cas Proteins Are Equal

When designing a gene editing (or base editing) experiment, it’s important to pick the right protein. Each Cas enzyme has its quirks—they differ in size and specificity, for example—but these differences are rarely quantified. Thankfully, Ilya Finkelstein’s lab at UT-Austin have published a paper, in Nature Biotechnology, that can help delineate the finer differences between Cas enzymes. In a massively parallel experiment, they benchmarked the cleavage and binding specificity for five SpCas9 variants and AsCas12a with “over 10,000 targets containing mismatches, insertions and deletions relative to the guide RNA”. The result? A better understanding of how mismatches between gRNA and DNA target alter the performance of a Cas protein (for example, “Engineered Cas9s, especially Cas9-HF1, dramatically increased cleavage specificity but not binding specificity compared to wtCas9.”)

Gene Expression Controlled with Light

Why use chemicals to control gene expression in a cell when you could use photons instead? Chemicals stick around for a long time; gene expression becomes “leaky”. Photons, on the other hand, can be easily tweaked, spatially controlled, and turned on and off (at the speed of light). To bring light-controlled gene expression to bacteria, the Avalos lab at Princeton has “developed a series of circuits for optogenetic regulation of the lac operon”, which they call OptoLAC, “to control gene expression from various [chemical] promoters using only blue light.” The study was published in Nature Chemical Biology.


🧫 Rapid-Fire Highlights

More research & reviews worth your time

Bacteria are incredibly resilient; when E. coli’s entire isoleucine biosynthesis pathway was deleted, cells rerouted existing pathways to circumvent the challenge (eLife). Open Access.

A new computational method uses Illumina reads to detect contaminations in plasmids. Checking DNA constructs before they enter cells could save days of experimental troubleshooting (Nucleic Acids Research). Open Access.

Inducible promoters were used to build simple genetic circuits that can measure metabolic burden “as it relates to RNAP resource partitioning” (Nucleic Acids Research). Open Access.

An “underdominance” gene drive was used to create fruit flies that cannot mate with one another—they are, technically, a new species (Nature Communications). Open Access.

41 inducible anti-repressors, responsive to fructose and D-ribose, have been created. They were then used to build NOT logical controls, including NOT, NOR, NAND, and XNOR, in E. coli cells (Nature Communications). Open Access.

Hemoglobin carries oxygen through the bloodstream; a new review outlines how microbes can be used to biosynthesize hemoglobin and meet a global demand (Trends in Biotechnology).

Cyanobacteria were engineered to produce trehalose, a sugar, directly from carbon dioxide. Further, the addition of a trehalose transporter (taken from an insect) enabled the cells to export 97% of the trehalose produced (Metabolic Engineering).

A biosensor in plants was used to quantify the uptake of sugar through SWEET transporters (what an amazing name) (bioRxiv). Open Access.

A feedback loop, built from pyruvate-responsive genetic circuits, was used to control the central metabolism of Bacillus subtilis. The circuit detects pyruvate and adjusts its actions accordingly. When implemented in cells, it more than doubled the production of glucaric acid (Nature Chemical Biology).

A CRISPR toolkit developed for yeast, featuring dCas9 and a variety of activation and repression domains, can be used to quickly design and perform CRISPR experiments (Scientific Reports). Open Access.

By building a genome from scratch, scientists can ask—and answer—a slew of fundamental, biological questions. A new review takes a look at what the assembly of Yeast 2.0 has helped reveal (Current Opinion in Systems Biology).

ADARs are proteins that bind to double-stranded RNA. A new preprint used a deep mutational scan to create ADARs for more specific RNA editing (bioRxiv). Open Access.

A new library of meganuclease-based transcription factors, created by mutations in critical regions of these proteins, was used to build genetic circuits in mammalian cells (ACS Synthetic Biology).


📰 #SynBio in the News


🐦Science Threads on Twitter

Imperial’s DNA Foundry is being used to test patients for SARS-CoV-2, as featured in this newsletter. Michael Crone, lead author on that study, explains more in this Twitter thread. 👇


I noticed, after writing this newsletter, that four of the five featured research items are from the Nature family of journals. While these journals do publish high-quality work, synthetic biology research does not (or, at least, should not) operate in an ivory bubble. I will work harder, in the future, to highlight research from more varied sources. As always, I welcome your feedback via direct Twitter message or comment. If you enjoy this newsletter, please share it with a friend.

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A version of these newsletters is posted on bioeconomy.xyz and my website, hiniko.io. Reach me with tips and feedback via Twitter direct message at @NikoMcCarty.