Cells in the human body have numerous chemical processes taking place all the time. When these go wrong, it can lead to disease. However, the chemical environment within cells has not been well understood. Yamuna Krishnan, Louis Block Professor of Chemistry and the College, and her team found a way to look inside organelles (small compartments within cells that perform specific functions) and to measure levels of ions or of sodium, potassium, and other elements. This precision approach could lead to earlier diagnoses and more effective medical treatments.
One hundred thirty-five years went by between the first measurement of ions in an acidic organelle called the lysosome and the second—Krishnan’s. The chemistry of cells had gone unexplored for so long because of how complicated it is to measure (not just detect) the chemical composition within a tiny organelle inside a living body. Not knowing ahead of time what kind of chemical environment they will encounter or what acidity levels—which interfere with ion sensing technology—scientists have to design around a lot of uncertainty.
Before Krishnan, no one had used DNA. The scientists in her lab twist minuscule strands of DNA together to engineer nanodevices that provide measurements of the chemicals inside cells. The unique structure of DNA enables Krishnan to build a range of functionalities into each device—like mechanisms to provide quantitative readouts of specific ions and a pH correction factor to protect against acidity—an improvement over existing protein imaging technology.
This ability to profile specific parts of cells will provide new insights into disease. For example, current research in neurodegenerative diseases like Alzheimer’s and Parkinson’s suggests that the plaques believed for many years to be the cause of the disease form because lysosomes, an organelle that breaks down waste in cells, are not functioning properly. Krishnan’s work can shed light on how these diseases operate at the cellular level.
The method she has established also allows more targeted drug delivery than was previously possible. The therapeutics company Macrologic, which Krishnan cofounded, leverages her DNA nanodevice technology to deliver drugs to a specific organelle within a specific cell type.
Among the numerous awards Krishnan has received for her groundbreaking research are the Infosys Prize in 2017 and the Director’s Pioneer Award from the National Institutes of Health in 2022. She was named a member of the American Association for the Advancement of Sciences in 2020.
“This is a technology that originates in the physical sciences, but all its applications are in biology and medical science,” says Krishnan. And the University of Chicago, where she joined the faculty in 2014, “was one of the few places on earth that has this borderless and barrierless movement across these two spaces.” She keeps in view the hope that her work will transform medicine: “That we can diagnose diseases much earlier than they are diagnosed today, that we can treat disease that we cannot treat today.”