Robots are replacing human workers in many sectors, including biology. The Functional Genomics Core at the UA provides robots and other equipment to allow researchers to collect large amounts of data that would be almost impossible through traditional methods.
Rajesh Khanna and May Khanna, a husband and wife research team and associate and assistant professors of pharmacology, respectively, are gearing up to run the FGC’s first compound screen for possible new pain drugs. In a compound screen, a chemical library is used to test different possible chemical compounds and their effect on a specific biological process, Rajesh Khanna said.
The chemical library has over 50,000 unique compounds. A robot will add each one of these compounds to a mixture of two purified proteins using robotic pipetting. Normally, these proteins interact in a way so that one protein changes the other to “activate” it, Rajesh Khanna said.
The Khannas are hoping to find a compound that can limit or prevent this interaction as a way to discover new pain-relieving drugs.
The interaction of the two proteins they are looking at adds a specific type of sodium channel to the cell, according to Rajesh Khanna. Like other ion channels, sodium channels are part of a system that sends messages between nerves and to the brain. For this specific channel, the message it helps send is perceived as pain.
People born without these channels are unable to feel pain. If a compound can prevent an increase in these channels through disrupting a protein interaction that normally adds channels into the membrane, then that compound could reduce the signaling of pain, or pain perception, Rajesh Khanna said.
Disrupting the interaction of the two proteins decreases the number of these channels in the membrane without rendering them non-functional. This equates to less pain with less chance of unwanted side effects, Rajesh Khanna said.
“It’s not blocking the channel directly but indirectly in a manner that may be useful,” Rajesh Khanna said.
May Khanna said that right now, they do not know what type of compound would be a good candidate to interfere with the protein interaction, but they do have 50,000 possible options to try.
Dealing with this much data and programming the machines require enormous amounts of logistics, according to Matthew Kaplan, an associate staff scientist and the facilities manager of the FGC. The compound screen requires “a year’s worth of troubleshooting up front,” Kaplan said. Instead of taking a year, the robot allows the researchers to screen all 50,000 compounds in just over two weeks.
Rajesh Khanna compared it to a chef cooking a meal for a large group of people. Everything must be choreographed to perfection, in the correct place and figured out far in advance. Except, instead of a gastronomic delight, the screen yields promising compounds that might mitigate pain.
Common chemical features between successful compounds can then be combined by chemists “like pieces of a jigsaw puzzle” to create more efficient compounds or modify the compounds to work better as drugs, May Khanna said.
However, the compound screen is only the first step of many. The compounds will then be put through more testing to determine if they will work in a live cell, in an animal model and maybe, finally, in humans, Rajesh Khanna said.
Big data, robotics, chemistry and biology all marry together in this process of drug discovery. As Kaplan said, “It’s a different way to do science.
_______________
Follow Amy Nippert on Twitter @DailyWildcat
