By 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.