Home/ Opinion / Online-views/  Those incredible DNA machines

Yamuna Krishnan is a popular speaker. Over the last five years, she has delivered lectures at scientific conferences and universities in Singapore, France, Germany, China, Israel, the UK, the US, Japan, Brazil and Mexico. In India, she shares her knowledge far and wide, from Shillong to Bhopal, with scientists and school students.

For someone with such a wide view of the world, the topic of her lectures is small, infinitesimally small—about 2 nanometres, or about 30,000 times thinner than a human hair. That’s the width of her subject matter: DNA.

DNA is the blueprint for life on earth, but as her work—and that of counterparts at the world’s best scientific institutes—reveals, it is time to regard the unmistakable double helix as a brick, construction material to build new devices to improve the quality of the life it created.

Krishnan, 39, is one of eight men and women honoured with this year’s Shanti Swarup Bhatnagar prize, awarded to Indian scientists under 45 years of age. In the weeks to come, Frontier Mail will tell you what these scientists do and why it is important.

A lean, lithe woman who runs 5km every day and swims for an hour when she can, Krishnan originally wanted to be an architect, a desire derailed at the Women’s Christian College, Chennai, when her maths marks were lesser than needed. Chemistry was “a compromise", one that served her well. “It was probably the best bend-in-the-road that ever happened to me," she wrote in an essay for the Indian Academy of Sciences. “It turned out that what seemed Hebrew to most was dazzlingly clear to me. I understood the language of molecules and reactions as if I had known it all along."

The new language revealed to Krishnan took her down a new path. With students at the laboratory she runs at the National Centre for Biological Sciences (NCBS) in Bangalore, she is creating a new genetic vocabulary to rewrite DNA. There are few in India who do what she does.

Krishnan, who did her doctorate at the Indian Institute of Science (IISc) and post-doctoral work at the University of Cambridge, UK, has shown how DNA can be artificially woven into longer strands, like a weaver’s tapestry, or a child’s matchstick house. “Just in the way we make architectures on the macro scale with matchsticks and fevicol, we can do the same with DNA," Krishnan tells me over email from Boston, where she has just given two lectures. Much like using fingers to assemble matchsticks, Krishnan uses chemicals called enzymes to manipulate strips, or sequences, of DNA to create nanoscale architecture: new structures smaller than 100 nanometres, invisible to the human eye. These DNA sequences can be copied, cut or pasted to create nanoscale machines of living matter. In contrast with non-biological options, DNA devices are biocompatible (unlikely to trigger the body’s immune system) and biodegradable (they can disintegrate harmlessly once their work).

This May, in a paper published in the journal Nature Nanotechnology, Krishnan and her team demonstrated for the first time how two nanomachines constructed from DNA could test acidity in two different places inside a living cell, an advance from running a single DNA nanomachine at a time. Abnormal cellular acidity is a marker for many diseases, and the use of DNA devices promises tools for future probes or disease therapies.

The remit of such research is wide. Nanoscale medical devices could, for instance, mimic viruses and introduce drugs directly into diseased cells. A chemical signal could prompt them to release their drugs—when and where needed.

“I see DNA architectures as wonderful probes to interrogate living systems to understand more about how cells function," says Krishnan, who as a child grew sugar and salt crystals and dissected flowers and frogs—with kitchen knives. She imagines custom probes to screen “scores and scores" of chemicals for drug-like activity. They could even be used to arrange interesting inorganic particles in precise, new ways to push the frontiers of physics and create new materials.

As a building material, DNA follows an inherent logic in the way it can be manipulated, fitted and refitted. There is a reasonably extensive library of molecular tools that allow DNA to be chopped and changed at ever-decreasing costs.

Lengths of DNA can be fitted together to form simple nets or more complex structures, using large molecules called nucleic acids, which work particularly well as scaffolding. This is how Krishnan’s group built the I-switch, a precursor to their nanomachine.

The I-switch comprises two rods of DNA, hinged, and tipped with a fluorescent compound. In cellular areas of higher acidity, the hinge closes and the edges glow red; in lesser acidity, it stays open, and the edges glow green—as it did when inserted into an earthworm. Her team has also built an icosahedron of DNA, a three-dimensional structure with 20 faces (in other words, bounded by 20 equilateral triangles). It looks other-worldly and beautiful in its extra-small world, but it has a serious purpose—to carry drugs into the cell. Why is it so complex? So it can carry more cargo and withstand degradation along the way.

As with so much in science today, the knowledge for DNA devices comes from the intersection of many disciplines, something that Krishnan learned early on at who studied at the IISc and Cambridge, where she “grew up" among physicists, engineers, computer scientists, biologists, chemists and mathematicians. “It helped me learn how to communicate with them in language we can both understand," she says. “This is important later when we realise that we cannot solve big problems with one discipline alone, or by yourself."

There is much testing and discovery ahead for Krishnan, her students and international collaborators. DNA devices are at an early stage of development. An equivalent might be the early 1950s, just before the first silicon transistor was commercialized. The demand for Krishnan’s speaking talents will not end any time soon.

Samar Halarnkar is a Bangalore-based journalist. This is a fortnightly column that explores the cutting edge of science and technology. Comments are welcome at frontiermail@livemint.com.

To read Samar Halarnkar’s previous columns, go to www.livemint.com/frontiermail

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Updated: 10 Jan 2014, 01:35 PM IST
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