January 6, 2026
Jeremy Sykes
Some of the deepest mysteries of biological function still remain locked in the microscopic world of the cell. Though much has been learned about how our internal organs form and function, individual cells each have their own internal organs, and scientists only have a minimal understanding of what these bizarre cellular inhabitants do.
“We are only scratching the surface of biology,” said Yamuna Krishnan, Louis Block Professor of Chemistry at the University of Chicago, in Nature Chemical Biology.
So Krishnan started creating nanodevices to look more deeply into those cells—providing new information to scientists studying neurodegenerative diseases. These nanodevices aren’t the swarms of tiny machines you see depicted in film, television, and social media. Instead, they are biological, formed from the basis for all life on Earth, DNA.
Unlocking Cellular Secrets
If you look at a cell closely, you’ll see a cell wall and cell membrane around the perimeter. Inside, you’ll see a nucleus, with a nucleolus in its center, perhaps some ribosomes and mitochondria floating about in a chemical soup called cytoplasm. Different cells have different structures in them, referred to in a general sense as organelles.
Most studies and FDA-approved drugs are focused on two major classes of protein, which exist on the outer cell surface membrane.
“That’s only about 2-5% of the total cell membrane,” Krishnan said. “The total membrane presence inside the cell is much larger, and the remaining membrane is from organelles and… we don’t know exactly what they do.”
Take lysosomes, for example. The lysosome is the end-product of endocytosis—when a cell engulfs external materials by enclosing them in a membrane and brings them inside. Previous research has determined that lysosomal abnormalities play a role in several neurodegenerative diseases, including Alzheimer's and Parkinson’s diseases.
“It’s the hardest organelle to probe because it is extremely acidic. It interferes with almost every ion sensing technology,” said Krishnan. “But it’s involved in a lot of things, like genetic defects.”
Recently, Krishnan’s University of Chicago laboratory developed a nanodevice to gain access to the lysosome. Krishnan’s nanodevices include small DNA duplexes that are only about 35 kiloDaltons and can reveal the defects in lysosomes. Each duplex is made up of only 3 to 4 DNA strands, but each strand carries a specific functionality relevant to whatever test is being conducted.
Neurological disorders are generally tricky to diagnose. Often, patients are forced to endure a raft of testing, some of which can be quite invasive, or in the case of imaging, may involve the use of radiation. Moreover, Krishnan said, some patients may already be living with Parkinson’s disease for ten years or more by the time they receive a confirmed diagnosis.
Nanodevice testing like Krishnan’s has the potential to make such diagnoses much more quickly. And if biological assay testing can move that diagnosis even a few years earlier, doctors and researchers will have much more time to combat the effects and to search for ways to ameliorate or reverse the damage.
Chemistry at the core
Biological tests aside—at the root of all intracellular movements is chemistry. Krishnan completed her Ph.D. in Chemistry at the Indian Institute of Science and performed her post-graduate work at Cambridge University. Krishnan was at Cambridge when Shankar Balasubramanian created what would become known as next generation DNA sequencing. That process made DNA sequencing many times speedier and less expensive and changed how labs worldwide experimented with DNA.
From Cambridge, Krishnan went back to India briefly, where she had a lab at the National Center for Biological Sciences. It was there that she developed her first prototype assay.
She came to the University of Chicago in 2014.
“Chicago has a fantastic medical school and research program right next to each other,” she said. “I felt that I needed to be in an environment where I could use chemistry to explore the full potential of what I had built.”
Recognizing a need for targeted assay testing, Krishnan patented her findings and began to explore the idea of a biotech startup. In 2018, she began Esya Labs. The company name was borrowed from a word in Sanskrit, meaning to probe, or medically examine, which is very appropriate for Krishnan’s line of biological markers.
The company has pioneered a way to create and market nearly a dozen biological sensors used for medical diagnosis. These sensors are various chemicals that are enclosed within walls of sculpted DNA, that, when put in contact with the cell sample, are consumed through a normal process called phagocytosis or endocytosis—eating and drinking for cellular life—necessary for each cell to perform its function and repair itself.
Once the chemicals (or sometimes DNA) have been ingested and are brought into the cell, their contents interact with the cell’s organelles. Sometimes various “dyes” are used that can be viewed with fluorescence microscopes—determining the volume of certain cell components by staining the cell contents with color perceived by the microscope.
The second part of the analysis is accomplished by comparing healthy cells’ chemistry with the cell samples, whether they are infected, diseased, or just damaged—the comparison to healthy cellular apparatuses is invaluable to working towards understanding.
Krishnan’s startup has taken off, thanks to grants funded by the Michael J. Fox Foundation for Parkinson’s Research and the Gates Foundation’s “Alzheimer's Disease Diagnostic Funding.” Esya now has proven products in market that can test subjects with just a few cells.
“If you are looking at languages,” Krishnan said, “then DNA itself is a very ancient language.” It’s a language that has built her DNA nanodevices and which are, at this very minute, probing the mysteries of the cell.
Yamuna Krishnan has been the recipient of many honors, including the Louis Block Professorship at the University of Chicago in 2024, the Director’s Pioneer Award from the National Institute of Health in 2022 and the Infosys Prize for Physical Sciences in 2017. Her work was also recognized in 2013 by the Shanti Swarup Bhatnagar Award, one of the most significant Indian science awards attainable. Krishnan visits Ashoka University every year to give talks to their undergraduates and sometimes school children via the Lodha Genius Programme. In her spare moments, Krishnan can be found at the pool, finding some alone time by swimming a few laps and concentrating on her technique.