Medicine has saved and improved the lives of countless people, a legacy that is continued in the physiology and neurobiology labs at the University of Connecticut today. Researchers, including undergraduate students, are working to understand how the human body functions in order to provide the building blocks for future treatments.
As an undergraduate student, Kevin Duignan, now a second year graduate student, said he stumbled upon Anastasios Tzingounis’ lab during an introduction to undergraduate research course. As he set up the “the rig,” he said undergraduate research was overwhelming at first because of his superficial understanding of the lab’s work, which involves the development of seizures and epilepsy.
“The best way to learn is dedicating several hours a day to it,” Duignan said while filtering a solution through a small tube and into a bath designed to mimic the brain’s internal environment. “There are a lot of different parts and procedures and a lot of that just takes practice. The understanding comes over time and it slowly clicks piece by piece over a semester or two.”
“The rig” on which Duignan works is a large structure with an attached microscope used for electrophysiology, the study of the flow of charged particles, called ions, in the body.
Duignan and other researchers in the lab use electrodes connected to mechanical arms to run electricity through individual brain cells on “the rig” in order to understand how conduits imbedded in the membranes of neurons, called ion channels, play a role in the development of seizures and epilepsy.
There are over 60 ion channels in the body, some that excite neurons and some that quiet them down, but the lab is focused on potassium ion channels, which are notable because they act as regulators of electrical signals. Tzingounis’s lab studies a specific group of channels called KCNQ potassium channels.
“They keep everything in check,” Tzingounis said.
As ions pass through these conduits, they create electric currents that allow different parts of the brain and body to communicate. Seizures and epilepsy occur when these currents become abnormal.
When mutations alter the DNA code responsible for the channels, they begin to lose proper function, potentially causing seizures. Mutations in potassium ion channels, unlike others, cause especially severe disorders, Tzingounis said.
“Currently we are using genetics and pharmacology to understand what is the function of these channels, how we can engage them, and what happens when they go wrong using mice as a model system,” he said.
In addition to electrophysiology, the lab uses imaging techniques to visualize the brain’s electrical signals after certain types of cells are engineered to lack potassium ion channels. The gene for the channel of interest is “knocked out” and the researchers observe how the network of electrical signals is altered.
“Think about watching a TV screen, but only having access to one pixel,” Tzingounis said. “This actually gives you another layer and shows you how the pixels interact with each other to create an image.”
While potassium ion channels play a big role in how the brain functions and the development of seizures and epilepsy, they are also found throughout body and could affect breathing, said Joannam Hawryluk, a graduate student in the lab.
“When people think about the body, they think of something going wrong in one place, but not how that affects the whole system,” Hawryluk said.
Today, Retigabine is given to patients to reduce seizures by opening potassium channels, which reduces the chance of nerve cells having sudden excitation events. The issue, Hawryluk said, is that potassium channels are found in many parts of the body and the drug often causes skin and digestive problems.
In the lab, Hawryluk studies KCNQ potassium channels and the drugs that affect them. She said her day-to-day routine starts with brain slices from mice and moves to electrophysiology and imaging.
With the guidance of Hawryluk and Duignan, Elizabeth Rodier, a fourth -emester biology major, is learning how to use “the rig.” This is her second week in the lab.
Lauren Colburn, a sixth-semester physiology and neurobiology major, may have been in the lab longer than Rodier but she said she understands getting into research at UConn could be a daunting task for undergraduates.
“My biggest advice is to be persistent and don't give up if a professor says there's no room in the lab. You have to ask a lot of professors,” Colburn said. “And eventually it will be very worthwhile and worth working for.”
Diler Haji is a campus correspondent for The Daily Campus and can be reached via email at firstname.lastname@example.org.