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CRISPR & Cane Toads Take Center Stage in New Yorker Article

In the January 18 issue of The New Yorker, Elizabeth Kolbert (Pulitzer Prize-winning author of ‘The Sixth Extinction’) discusses how CRISPR and gene drives can be used to eradicate invasive species, or bring species back from extinction (CRISPR and the Splice to Survive). The highlight of the story, at least for me, was its discussion of an ongoing Australian effort to mitigate the looming threats caused by an invasive amphibian.

Towards the start of the article, Kolbert recounts a trip to the BSL-4 Australian Animal Health Laboratory, outside Melbourne. Inside, Mark Tizard and Caitlin Cooper are devising new strategies to rid Australia of Rhinella marina, or cane toads. …

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☀️ Good morning

Omne ignotum pro magnifico est.

The Quest to Shrink Genomes

The synthetic yeast project is an international effort to build the world’s first synthetic, eukaryotic genome. Each chromosome in Saccharomyces cerevisiae is being chemically-synthesized in labs across the world. And along the way, each chromosome is receiving some bonus features, including short DNA sequences flanking each gene that enable genes to be cut out and randomly rearranged, or “scrambled”, around the genome.

For a new study, published in Genome Biology, researchers at the Shenzhen Institute of Synthetic Biology and Manchester Institute of Biotechnology “scrambled” the left arm of chromosome 12, called synXIIL, using those added DNA sequences. The chromosome was “rearranged” several times, and the team found that 39 out of 65 nonessential genes essentially dropped out after scrambling, and could be removed completely. The project is still ongoing, and the international consortium plan to meet up and put all their chromosomes together. When that happens, perhaps they could use this method to shrink down the genome en masse. Open access. …

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The Lab Leak Idea Returns

The biggest story this week was the New York magazine cover story, touting the theory that the coronavirus was made in, and leaked from, a Wuhan laboratory (Link to story). It was followed, a few days later, by a Forbes report stating that China had denied entry for an international team aiming to study the origins of SARS-CoV-2.

The New York article focuses largely on gain-of-function studies, and how they might be associated with the emergence of SARS-CoV-2. The article is labeled as investigative journalism but, in my opinion, should not qualify as such. Much of its details were previously known and covered by the Washington Post and others. Multiple sources quoted in the article state that there’s no evidence one way or the other (lab leak vs. ‘natural’) but, nonetheless, the author makes his biases clearly known. …

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☀️ Good morning

And a happy new year to you. I hope that this newsletter, sent on the first workday of the new year (I know, yuck), will help round in these hopeful days. It includes some of my favorite bits of research and reviews from the last few weeks.

Phage Genome in a Test Tube

A few weeks back, I wrote an article about a brilliant study from Greg Lohman’s lab at New England Biolabs. In PLOS ONE, his group reported that they could “stitch together” 35 unique pieces of DNA, in a single tube. …

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The Protein Folding Problem…Solved?

DeepMind, based in beautiful London, not far from King’s Cross, announced that their artificial intelligence program, called AlphaFold, had provided “a solution to a 50-year-old grand challenge in biology,” namely, protein folding. That claim is based on results from the 14th Critical Assessment of protein Structure Prediction, or CASP, challenge. The AlphaFold team measured the accuracy of their AI’s predictions via a Global Distance Test, or GDT, that ranges from 0–100.

“In simple terms, GDT can be approximately thought of as the percentage of amino acid residues (beads in the protein chain) within a threshold distance from the correct position,” wrote the AlphaFold team on their blog. “According to Professor Moult, a score of around 90 GDT is informally considered to be competitive with results obtained from experimental methods.” AlphaFold achieved a median score of 92.4 …

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This Thanksgiving, I’m grateful to you, my readers. In the convoluted chaos of the internet, I know that you could be reading many things. Thank you for reading this. Reach out on Twitter with feedback and questions.

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DNA Cloning Goes Full-Auto

It’s midnight in the lab. All your co-workers have gone home. You’re alone at the bench, fearful that a security guard will arrive at any moment and kick you out. …

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A Gene Therapy, Tested on Dogs, Has Issues

For CRISPR-based gene therapies to work, you first need to squeeze a Cas protein and guide RNAs into a teeny tiny virus. Then, that packaged virus — bearing its gene-editing payload — has to be inserted into the body.

The most common “delivery vehicle” for gene therapies are AAVs, or adeno-associated viruses. Long considered to be extremely safe, a new study, the most in-depth of its kind, is shedding new light on their long-term efficacy.

Researchers injected nine dogs with hemophilia A, a type of bleeding disorder, with an AAV “payload”. Then, they followed the dogs over a period of ten years. The gene therapy was extremely effective. The nine treated dogs, together, only had seven bleeding episodes during the study period. Eleven untreated dogs with hemophilia, by comparison, had about twelve bleeding episodes each — every single year. …

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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. …