Heat-Protecting Gene in Corals & Human Cells Get an Upgrade…from Tardigrades
By: Niko Mccarty
Tags: Tech, Newsletter, News, Future, Science

NEWSLETTER

Heat-Protecting Gene in Corals & Human Cells Get an Upgrade…from Tardigrades

This Week in Synthetic Biology (Issue #15)

Underwater corals. Credit: Pexels on Pixabay

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Heating Breakthrough in Corals

As the earth heats, and the Great Barrier Reef melts away, scientists are scrambling for deeper insights into heat-tolerance in coral — specifically, which genes help corals cope with higher temperatures, and could gene editing be used to create heat-resistant variants?

A gene in fertilized coral eggs (Acropora millepora), called Heat Shock Transcription Factor 1 (HSF1), was mutated with CRISPR/Cas9. After one injection of the CRISPR/Cas9 components, 90% of the eggs carried mutations in that gene, causing drastic changes in how well the coral could handle heat later on. “The mutant larvae survived well at 27 °C but died rapidly at 34 °C,” the authors wrote. The higher temperature did not, however, cause any damage to normal, un-edited corals. The authors conclude, therefore, that HSF1 “plays an important protective role” in these stunning creatures. This study was published in PNAS. Link

Human Cells Upgraded with Tardigrade DNA

Astronauts and flight-attendants alike are bombarded with radiation. In one study, 1.2% of male flight attendants reported that they had melanoma, a rate nearly twice as high as the general population. Female flight attendants, similarly, have reported a skin cancer incidence that is four times higher than the general population. To protect these high-flying professionals, some scientists are turning to…tardigrades.

These little “sea bears” are so hardy that they can “survive up to 5kGy of ionizing radiation and also survive the vacuum of space,” according to the authors of a new preprint, posted on bioRxiv. For context, a typical abdominal x-ray is just 0.7 milligrays, or about 7 million times less radiation than tardigrades can withstand.

The researchers studied a damage suppressor protein from the tardigrades, called Dsup, that helps repair damage to DNA caused by ionizing radiation. They transplanted Dsup into human cells, grew the engineered cells in a dish, and found that the cells became more tolerant to apoptosis — or cell death — signals. The authors think that their “methods and tools provide evidence that the effects of the Dsup protein can be potentially utilized to mitigate such damage during spaceflight.” Link

A tardigrade swims by. Credit: GIF Maker/Giphy

Rapid Evolution Creates New TrpB Proteins

Creating proteins with new functions can, at least in the natural world, take hundreds or thousands of years of evolution. One protein begets another, through mutations, slowly unraveling a sea of new properties that help organisms adapt and survive in their environments.

But evolution can also be “jump-started” in the laboratory, and kicked into overdrive using relatively modern approaches called directed evolution. This technique — using evolution to design new proteins — earned Frances Arnold a share of the 2018 Nobel Prize in Chemistry.

In a new study, emanating from a collaboration between the labs of Chang Liu and Frances Arnold, a method for continuous, directed evolution, called OrthoRep, was used to create new variants of the tryptophan synthase β-subunit protein. This enzyme is important because it synthesizes L-tryptophan from indole and L-serine. Over 100 generations of the directed evolution experiment, the researchers created new TrpB enzymes that had higher activities, could use different indole analogs, or could work at different temperatures. This study was published in Nature Communications, and is open access. Link

Engineered Bacteria Respond to Inflammation Signals

Microbes that live in the human gut can be engineered to release medicines, or sense diseases. They are basically tiny, programmable doctors that could, one day, be used to treat all kinds of ailments.

In a new preprint, posted to bioRxiv, scientists at Caltech engineered E. coli Nissle cells with an AND logic gate that triggers a gene’s expression when two signals are present: tetrathionate (an inflammatory biomarker) and IPTG. The authors “report 4–6 fold induction with minimal leak when both signals are present.” These are interesting preliminary results, based on experiments done in flasks and tubes, and the next step will be to take these engineered cells, and see if they can actually sense inflammation inside of, say, a mouse gut. Link

Study Evaluates CRISPR-Cas Systems for RNA Editing

The gene-editing tool, CRISPR-Cas9, can be adapted to cut both DNA and RNA inside of living cells. Its utility for DNA-editing is well known, but RNA-editing applications have not been studied as carefully.

Catalytically inactive Cas9 — that is, Cas9 that cannot cut DNA, but can still recognize and bind to a genetic target — can be fused to a protein called ADAR (adenosine deaminases acting on RNA) to make single-letter changes in RNA. These dCas9-ADAR proteins can switch A to I, for example, but it turns out that they have some issues.

The researchers of a new study from the Yeo lab at UC San Diego say that the “Cas-based ADAR strategies have distinct transcriptome-wide off-target edits”. They also performed experiments to figure out how to best design guide RNAs to target a specific nucleotide in an RNA strand. They found that, even without a spacer sequence, Cas9-ADARs could still edit RNA. This study was published in Cell Reports, and is open access. Link