Making aptamers with biology's help - C&EN Global Enterprise (ACS

Jan 23, 2017 - Scientists simulate evolution in the lab by introducing mutations iteratively into biomolecules such as nucleic acids and selecting for...
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NUCLEIC ACIDS

How does the universe store iron? A Japanese research team launched a rocket loaded with lasers and a nucleation chamber more than 300 km above Earth’s surface to investigate how the universe might stow its solid iron. Although the mission didn’t discover interstellar iron troves, the researchers did find one form the element is unlikely to take: pure iron granules (Sci. Adv. 2017, DOI: 10.1126/ sciadv.1601992). Iron-rich particles floating in the expanses between stars likely play a role in catalyzing the universe’s chemical evolution, but scientists are uncertain about the forms solid iron takes in interstellar space. Pure iron particles now seem an unlikely option, according to the research team led by Yuki Kimura of Hokkaido University. The team evaporated iron atoms within a nucleation chamber that allowed researchers to control temperature and pressure. Flying the chamber in parabolic patterns aboard a rocket allowed the team to emulate the microgravity of space. The famed “vomit comet” aircraft used to train astronauts relied on the same patterns, but rockets can counteract gravity’s tug for longer times. The team observed pure iron granules forming using a laser interferometer, but such events were exceedingly rare. Only about one in every hundred thousand iron collisions resulted in atoms sticking together and nucleating particles, the team reports. This low sticking probability surprises Bruce T. Draine, an astrophysicist at Princeton University, although he’s not sure how much the finding tells us about the forms interstellar iron does take. Draine and Kimura’s team think that iron atoms are most likely captured by existing particles, such as silicates and carbonaceous grains, floating through space.—MATT DAVENPORT

Making aptamers with biology’s help Scaffolds from riboswitches help aptamers work better in cells Scientists simulate evolution in the lab sors that worked inside and outside cells. by introducing mutations iteratively into “Till now there hasn’t been a robust set biomolecules such as nucleic acids and of design principles that one could use to selecting for desired properties. When quickly generate a diverse set of aptamcarrying this process out specifically on er-based biosensors that also fold properly RNA molecules, they can evolve the RNAs in cellular contexts,” says Herman O. Sinto bind specific small molecules. But many tim, who develops aptamer-based sensors of these so-called aptamers don’t bind at Purdue University. “Using aptamer folds well to their targets when put inside cells that have undergone extensive biological because they don’t fold into stable structures. “As we solved the structures of naturally occurring aptamers, we noticed they had much more complex secondary and tertiary structures” than versions made in the lab, says Robert T. Batey of the University of Colorado, Boulder. “So we decided to use these naturally occurring RNA folds as starting points” for producing more stable artificial aptamers. To prove their concept, Batey and coworkers used RNA seWhen Batey’s team evolved a guanine-riboswitch quences from naturally occuraptamer (left) into an aptamer that binds ring ribozymes and riboswitches 5-hydroxytryptophan (5HTP, right), only the as scaffolds to evolve aptamers ligand-binding pocket changed significantly. that bind amino acids and other small molecules used to make neurotransevolution as scaffolds and developing mitters (Nat. Chem. Biol. 2017, DOI: 10.1038/ methodologies to limit mutations of such nchembio.2278). The resulting aptamers scaffolds during the aptamer evolution and are selective for these precursor molecules selection process is a surprisingly simple over structurally similar amino acids and approach, yet it hadn’t been demonstrated the neurotransmitters themselves. until now.” One challenge, Batey says, was find“Given the great diversity of natural ing an enzyme that would not introduce riboswitch and ribozyme systems that mutations that disrupt the scaffolds. For have been characterized, this idea really instance, he says, the original reverse tranhas the potential to be transformative and scriptase the team tried quickly destroyed widely applicable to a whole host of small the scaffold by introducing mutations that molecule sensors and devices in the cell,” caused the RNAs to misfold. The team had says Maria DeRosa, who studies aptambetter luck with a recently discovered reer-based sensors and catalysts at Carleton verse transcriptase. University. To convert their aptamers into sensors, Ming Chen Hammond, who develops the researchers connected an evolved apRNA-based biosensors at the University tamer to a second fluorophore-binding apof California, Berkeley, says the study protamer. When the first aptamer binds its tar- vides a “master class” on how to make such get, the second aptamer is able to bind the novel aptamer sensors. “Many of us dream fluorophore, which emits light in response. of having our own riboswitch or biosensor A third piece—an attached transfer RNA for measuring any given metabolite in scaffold—stabilizes the structure in cells. cells,” she says. “This takes us a step closThe researchers characterized three sener.”—CELIA ARNAUD JANUARY 23, 2017 | CEN.ACS.ORG | C&EN

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CREDIT: NAT. CHEM. BIOL.

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