Yamuna Krishnan, who turned 39 last week, celebrated her birthday in style. The Bangalore-based researcher gifted the world a tool that could play at being a detective within a living cell and help scientists develop the best treatment for a disease.

Building on their earlier work, Krishnan and her students at the National Centre for Biological Sciences (NCBS) in Bangalore demonstrated that two or more extremely tiny DNA devices can be despatched inside a cell to report on goings-on within. The NCBS scientists first created such nanodevices in 2009 by cooking and cooling commercially available DNA strands. But in the latest work, which appeared in Nature Nanotechnology recently, they successfully sent not just one but two DNA nanomachines inside a living cell. And these tiny devices, which are 14 nanometres (nm) long and 2nm in diameter, helped the scientists accurately measure the pH values of subcellular locations where they were parked.

The pH value is a measure of a liquid’s acidic or alkaline nature. While the pH value of pure water is 7, a pH value of 1 would mean highly acidic and 14 most alkaline. “The pH value is a good correlate. It not only reports on the location of the protein inside the cell but also gives a measure of the environment around it. Acidity is an indicator of how well things are going. So, measuring the pH can tell you whether a cell is absolutely normal or under the weather,” says Krishnan.

“These DNA-based nanomachines are pretty easy to make. One needs to take the same amount of two different DNA strands in a solution or in normal water with a little bit of potassium chloride and mix. Uniform heating to 90 degrees and subsequent cooling over three hours make these nanodevices ready,” says Souvik Modi, first author of the paper, who is currently pursuing his postdoctoral studies at University College London.

Living cells are amazingly organised. They have several compartments at definite locations doing specific jobs. The pH value of each of these sub cellular compartments is different, depending on its function. For instance, the pH value of lysosomes — where waste materials and cellular debris are broken down — is 5.0, whereas in mitochondria — the power producers in a cell — the normal pH is 7.8.

“DNA nanodevices can be made to latch onto specific proteins. At any point in time, it is possible to know where these proteins are as the nanodevices work like some sort of molecular GPS,” says Krishnan. Also, they can let scientists know the pH of the location. “If the pH is found to be different from normal, we know something is amiss,” she adds.

Having more than one nanodevice inside a cell helps give a better picture of the situation. “It is like when two reporters report from different locations in a city where a disaster has struck. It helps in getting a deeper understanding of the problem,” explains Krishnan.

Souvik Modi (top) and Yamuna Krishnan

The application potential of the technique is humongous. It can be a great tool for drug discoverers. “Suppose we have many candidate drug molecules that need to be tested against, say, a viral infection or a bacterial infection. If we know which protein is the target of the drug molecule, a DNA nanomachine can be latched onto the protein. Whichever drug molecule brings the pH back to normal would be the potential candidate,” says Krishnan, who has been working on DNA-based nanodevices since 2005.

Is it difficult to identify which protein should be the target, since a cell has tens of thousands of proteins? “Don’t the cops easily identify suspects after a crime is committed in a city where millions live? Similarly, scientists can identify which proteins should be monitored,” replies Krishnan.

The NCBS scientist is liberal in doling out credit to her students for this significant piece of work. “This was made possible because of the interdisciplinary nature of our team. We have people with varied specialisations such as chemistry, mechanical engineering, genetics and biotechnology collaborating for this research,” says Krishnan who is a chemist specialising in nucleic acids.

“This may give us the next generation probes for sensing intracellular signals,” says Satyajit Mayor, a NCBS scientist who is not directly involved in this study.