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The Crystal Jelly Unveils Its Brightest Protein Yet
Aequorea victoria, the crystal jelly, hovers in the waters off the coast of California. Decades ago, Osamu Shimomura noticed that these jellies emit a faint, green light. So he took pieces from one of them, did some experiments, and found the protein responsible for the glow. That protein—GFP—is now used in thousands of labs to light up the insides of microscopic cells. Shimomura shared the 2008 Nobel Prize for that work, along with Martin Chalfie and Roger Tsien, who died in 2016.
Now, it looks like the crystal jelly hasn’t given up all of its secrets just yet.
In a new study, nine previously unstudied proteins, also from Aequorea victoria and a related species, were reported. Several of the new fluorescent proteins have quirky characteristics, too. One of them is “the brightest GFP homolog yet characterized”, while another protein can respond to both UV and blue light. The scientists even found a couple of purple and blue-pigmented chromoproteins. The findings are further evidence that, in the darkness of the oceans, scores of mysteries remain to be discovered. This work was published Nov. 2 in the open-access journal PLoS Biology. Link
Will DNA Replace Grocery Store Barcodes?
A standard barcode—think grocery store rectangle, with black-and-white lines—contains 11 digits. Mixing up those digits in every possible way gives about 100 billion possible combinations. That’s a lot, but it’s not nearly as many combinations as what a barcode made from DNA could provide.
A new study, published in Nature Communications, reports a molecular, DNA tagging system that could become the future of barcodes. The DNA was dehydrated, which made it more stable, and the sequences were read out in just a few seconds with an Oxford Nanopore MinION, a small, portable DNA sequencer. To facilitate that speed, the authors came up with some clever ways to avoid complex, computational analysis of the DNA signals; they were able to read the barcodes directly from the raw sequence data. This study was published Nov. 3 and is open access. Link
Bacteria Produce Tyrian Purple Dye (From Sea Snails!)
As early as 1570 BC, the Phoenicians were dying fabrics with Tyrian purple. To make the dye required a process so intensive as to be nonsensical; as many as 250,000 sea snails (Bolinus brandaris) had to be smashed into goop to make just one ounce of dye. It was a color reserved for royalty, and literally worth more than its weight in gold.
Thank goodness, no more snails need to be smooshed to make Tyrian purple dye. Engineered E. coli bacteria can now make the dye’s predominant chemical, called 6,6'-dibromoindigo. To achieve this, scientists from Seoul National University added several genes to the bacteria; a tryptophan 6-halogenase gene, a tryptophanase gene and a flavin-containing monooxygenase. That’s a mouth garbling sentence, but I promise the result is easier to understand: the cells were able to produce 315 mg of 6,6'-dibromoindigo per liter in flasks, using tryptophan—an animo acid—as the chemical precursor. This work was published Nov. 2 in Nature Chemical Biology. Link
79 Different Cas9 Proteins Were Tested. Some Are Wicked Cool
Cas9 is maybe the most famous protein on earth. It’s like, the Kim Kardashian of the protein world. If there was a magazine for proteins, Cas9 would be on its cover. Oh wait, that already happened.
There’s a lot of different Cas9 proteins, but not all of them have been characterized. In a new study, scientists identified, and tested, 79 different Cas9 orthologs—proteins taken from different species, but that have the same function—and figured out how they recognize and cut DNA. Intriguingly, some of the Cas9 proteins only worked at specific temperatures; Cme2 Cas9, for example, “was only robustly active from ~30 °C to 55 °C suggesting the possibility of temperature-controlled DNA search and modification.” This study was published Nov. 2 in Nature Communications, and is open access. Link
CRISPR Shuts Down Fertilized Eggs
I didn’t know about the birds and the bees until my parents sat me down and told me. But if you’re wondering, a typical pregnancy starts like this: a fertilized egg latches on to the endometrium in the uterus. That activates a flood of genes to turn “on”, including one called leukemia inhibitory factor, or LIF. A new study has figured out a way to cut off fertility—with CRISPR—by targeting LIF and switching it “off”. The reason this is cool is because, well, the CRISPR-Cas9 system is photoactivatable, meaning it can be switched on with an LED.
The scientists, from Keio University in Tokyo, think that their work could prove useful in basic science research that probes the molecular signals underpinning this process. The study was published Nov. 2 in the journal PNAS, and is open access. Link
🧫 Rapid-Fire Highlights
More research & reviews worth your time
- Antibodies can be targeted to the Receptor Binding Domain of SARS-CoV-2, the virus that causes COVID-19, to block the virus from entering cells. But antibodies are hard to make. A new preprint describes a cell-free platform—internal ‘goo’ extracted from cells—that can be used to quickly produce antibodies. The method was eventually used to identify more than 800 “predicted binder families”, or antibody structures that might be able to bind to, and inhibit, the coronavirus. bioRxiv (Open Access). Link
- A new review discusses the tools available to design and create ‘designer’ proteins. The title of the article has a weird, political uprising vibe: “Arming Yourself for The In Silico Protein Design Revolution.” Trends in Biotechnology. Link
- It turns out that S. cerevisiae—Baker’s yeast—have metabolic pathways that can be used to metabolize methanol. Those findings emerged from a new study that used laboratory evolution (in which scientists selectively passage cells, over time) and carbon-13 to trace metabolites through yeast cells. Nature Communications (Open Access). Link
- A beautiful review takes a deeper look at how molecular signals can be used to create synthetic, multicellular systems. The authors also discuss feedback loops, chemical messaging systems, and other fun synthetic biology topics. Current Opinion in Systems Biology (Open Access). Link
- New tools to perform “multiplex” genome editing—in which multiple genes are targeted, and modified, at once—have been reported for wheat. If anyone uses this on wheat, and bakes a loaf of bread, please send me your recipe (and a sample). Plant Biotechnology Journal. Link
- By mixing Cas9 with Cre-lox (a classic gene editing system, which has long been used to create engineered mice for medical studies), many different bacterial species can be precisely engineered. In this study, authors used the system to engineer four different species. PLoS One (Open Access). Link
- A new gene drive for Anopheles stephensi mosquitoes was reported by the James lab. This one targets and disrupts a mosquito gene required for survival, as well as a gene involved in eye color. Read the writeup from the lead author, which describes it far better than I could do in ~100 words. Nature Communications (Open Access). Link
- Engineered cells are stressed out, and for good reason. Some scientist, towering over a bench, has introduced all this foreign DNA and said, “Go on, take this! And make something with it.” The cell is, understandably, placed in a precarious position, teetering between a normal existence and a call to manufacture some new, foreign protein. Now, a new study helps alleviate that stress. By using quorum sensing signals and genetic circuits, scientists were able to redistribute cellular resources in a pathway agnostic way. The method could prove useful for all sorts of metabolic engineering projects. Nature Communications (Open Access). Link
- A genetic circuit—containing just 7,700 bases of DNA—was delivered, by virus, to bladder cells. The circuit can differentiate cancer cells from non-cancer cells, using a “miniaturized” genetic logic gate. Nature Communications (Open Access). Link
- Working in a lab means collecting reams of data. Notebooks, computer files, and printouts of PCR experiments. That disorganized data, applied to something that requires a lot of troubleshooting (like building a genetic circuit that works as expected), slows down progress. Now, a new data management system can help organize all that data. bioRxiv (Open Access). Link
- To keep a genetically-modified organism (GMOs—gasp!) from leaving the lab, some labs have been hard at-work developing “biocontainment” systems; molecular checks and balances that can make a cell’s life outside of its flask untenable. A new study uses fluoride to keep engineered yeast in check. Without fluoride around, the engineered yeast behave identically to their non-engineered cousins. But when fluoride is present in the environment, the “biocontained” yeasts slow their growth. That means that, were a yeast to escape down the drain, it may swiftly meet its demise in the public water system. Nature Communications (Open Access). Link
- By decoupling a cell’s normal processes from its engineered functions—like producing a recombinant protein—noncanonical amino acids can be incorporated into proteins at higher yields. ACS Synthetic Biology. Link
- A new study has reported a coupled pair of engineered bacterial strains (E. coli) that repress each other; that “mutual inhibition”, alone, was enough to “produce stable domains of gene expression in response to dynamic morphogen gradients”. Nature Communications (Open Access). Link
- All mammals—and yeasts and worms, too—have something called an “unfolded protein response” that kicks on when a cell gets stressed out, and triggers a response that moves around resources in the cell to manage that stress. A new study reports several different biosensors that can detect and measure the unfolded protein response, including one genetic biosensor that is just 98 bases in length. Using that sensor, the authors “demonstrate its ability to accurately discriminate between cells expressing different heterologous proteins and at varying production levels.” bioRxiv (Open Access). Link
📰 #SynBio in the News
- I wrote an article, with Suzy Beeler, about our published work in eLife, and how our group at Caltech is working to “decipher the language of genomes”. Check it out. Caltech Letters. Link
- A gene therapy trial for Angelman syndrome, “a rare genetic condition related to autism”, was halted after two participants temporarily became unable to walk. Spectrum. Link
- Academic outlooks look increasingly bleak for many scientists. That’s why some researchers are carving out their own self-employed niches. Bioeconomy.xyz. Link
- London-based LabGenius, a company that uses robots and AI to design new materials and drugs, was featured in an article by Jeremy Kahn. Fortune. Link
- Henrietta Lacks’ cells, taken during an operation without her or her family’s knowledge, have been used to develop cancer treatments and make vaccines. Only now are giant corporations atoning for the ethical violations that enabled that work. Future Human. Link
- Basic science alert: Spider silk is cool, and scientists continue to unravel its “gloopy” secrets. Learn how silk gets made inside of a spider’s glands. New York Times. Link
- Ginkgo Bioworks released their second edition of “Grow”, a magazine that focuses on synthetic biology. This issue is all about Beauty. Grow By Ginkgo. Link
- A weekly news roundup, focused on “everything bringing humans closer to a food-secure future”, highlights a company that is making synthetic honey, and a seed bank for CRISPR-modified seeds. Future Human. Link
- CRISPR may not be ready—in some scenarios—for editing human embryos. Emily Mullin reports on two recent preprints; in one, which aimed “to fix a mutation in a gene called EYS”, an entire chromosome was inadvertently deleted. Future Human. Link
- Guide RNAs come in many different flavors. A new technology feature, by Vivien Marx, explains. Nature Methods. Link
- An article featuring companies like Octarine Bio and Hyasynth explores synthetic biology for cannabinoids. Labiotech.eu. Link
- PerkinElmer bought Horizon Discovery, one of the leading CRISPR therapy companies, for $383 million. Fierce Biotech. Link
🐦 Tweet of the Week
It’s been a stressful week. So instead of thinking about science, why not sit back, relax, and have a refreshing beer made from “CRISPR-edited yeast”? 👇