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TECHNOLOGY FEATURE
23 January 2023
Seven technologies to watch in 2023
Nature’s pick of tools and techniques that are poised to have an outsized impact on science in the coming year.
Michael Eisenstein
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A NASA engineer examines JWST mirror segments at NASA's Marshall Space Flight Center.
The James Webb Space Telescope’s 6.5-metre primary mirror (6 of 18 segments shown) can detect objects billions of light years away. Credit: NASA/MSFC/David Higginbotham
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From protein sequencing to electron microscopy, and from archaeology to astronomy, here are seven technologies that are likely to shake up science in the year ahead.
Single-molecule protein sequencing
The proteome represents the complete set of proteins made by a cell or organism, and can be deeply informative about health and disease, but it remains challenging to characterize.
Proteins are assembled from a larger alphabet of building blocks relative to nucleic acids, with roughly 20 naturally occurring amino acids (compared with the four nucleotides that form molecules such as DNA and messenger RNA); this results in much greater chemical diversity. Some are present in the cell as just a few molecules — and, unlike nucleic acids, proteins cannot be amplified, meaning protein-analysis methods must work with whatever material is available.
Most proteomic analyses use mass spectrometry, a technique that profiles mixtures of proteins on the basis of their mass and charge. These profiles can quantify thousands of proteins simultaneously, but the molecules detected cannot always be identified unambiguously, and low-abundance proteins in a mixture are often overlooked. Now, single-molecule technologies that can sequence many, if not all, of the proteins in a sample could be on the horizon — many of them analogous to the techniques used for DNA.
Edward Marcotte, a biochemist at the University of Texas at Austin, is pursuing one such approach, known as fluorosequencing1. Marcotte’s technique, reported in 2018, is based on a stepwise chemical process in which individual amino acids are fluorescently labelled and then sheared off one by one from the end of a surface-coupled protein as a camera captures the resulting fluorescent signal. “We could label the proteins with different fluorescent dyes and then watch molecule by molecule as we cut them away,” Marcotte explains. Last year, researchers at Quantum-Si, a biotechnology firm in Guilford, Connecticut, described an alternative to fluorosequencing that uses fluorescently labelled ‘binder’ proteins to recognize specific sequences of amino acids (or polypeptides) at the ends of proteins2.
(Top) Natural embryo at embryonic day e8.5, (bottom) synthetic embryo at day 8 of development.
Researchers can now make synthetic embryos in the laboratory (bottom) that resemble natural, eight-day-old embryos (top).Credit: Magdalena Zernicka-Goetz Laboratory
Other researchers are developing techniques that emulate nanopore-based DNA sequencing, profiling polypeptides on the basis of the changes they induce in an electric current as they pass through tiny channels. Biophysicist Cees Dekker at Delft University of Technology in the Netherlands and his colleagues demonstrated one such approach in 2021 using nanopores made of protein, and were able to discriminate between individual amino acids in a polypeptide passing through the pore3. And at the Technion — Israel Institute of Technology in Haifa, biomedical engineer Amit Meller’s team is investigating solid-state nanopore devices manufactured from silicon-based materials that could enable high-throughput analyses of many individual protein molecules at once. “You might be able to look at maybe tens of thousands or even millions of nanopores simultaneously,” he says.
Although single-molecule protein sequencing is only a proof of concept at present, commercialization is coming fast. Quantum-Si has announced plans to ship first-generation instruments this year, for example, and Meller notes that a protein-sequencing conference in Delft in November 2022 featured a discussion panel dedicated to start-ups in this space. “It reminds me a lot of the early days before next-generation DNA sequencing,” he says.
Marcotte, who co-founded the protein- sequencing company Erisyon in Austin, Texas, is bullish. “It’s not really a question of whether it will work,” he says, “but how soon it will be in people’s hands.”
James Webb Space Telescope
Astronomers began last year on the edges of their collective seats. After a design and construction process lasting more than two decades, NASA — in collaboration with the European and Canadian space agencies — successfully launched the James Webb Space Telescope (JWST) into orbit on 25 December 2021. The world had to stand by for nearly seven months as the instrument unfolded and oriented itself for its first round of observations.
It was worth the wait. Matt Mountain, an astronomer at the Space Telescope Science Institute in Baltimore, Maryland, who is a telescope scientist for JWST, says the initial images exceeded his lofty expectations. “There’s actually no empty sky — it’s just galaxies everywhere,” he says. “Theoretically, we knew it, but to see it, the emotional impact is very different.”
JWST was designed to pick up where the Hubble Space Telescope left off. Hubble generated stunning views of the Universe, but had blind spots: ancient stars and galaxies with light signatures in the infrared range were essentially invisible to it. Rectifying that required an instrument with the sensitivity to detect incredibly faint infrared signals originating billions of light years away.
The final design for JWST incorporates an array of 18 perfectly smooth beryllium mirrors that, when fully unfolded, has a diameter of 6.5 metres. So precisely engineered are those mirrors, says Mountain, that “if you stretched a segment out over the United States, no bump could be more than a couple of inches [high].” These are coupled with state-of-the-art near- and mid-infrared detectors.
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