Sleep-Related Epilepsy

What biomedical issue did you address in your research, and what did your studies find?

My graduate work aimed to identify some of the underlying factors that trigger sleep-related epilepsy. In particular, I was interested in mutations that alter membrane proteins of neurons. The mutations affect the way neurons communicate with each other, tipping the balance between nerve cell excitation and inhibition. This imbalance produces seizures. My research asked: How does a specific mutation affect the function of the membrane proteins — specifically the ion channels known as acetylcholine receptors, or AChRs — that relay communication between neurons? And how can we use these findings to explain the mechanism that causes sleep-related hyperkinetic seizures?

Embedded in the membranes of cells, AChRs are cylindrical proteins with openings on both sides, like a straw. The channel stays closed most of the time unless it is activated by a ligand that prompts it to widen, resulting in the excitation of the cell. The opening and closing behavior can be monitored by the electrical signal it produces. I used a technique called single-channel patch clamp electrophysiology, which detects the opening and closing of the channel, and measured it in real time at the speed of microseconds.

I found that the epilepsy-causing mutation prolongs by 11-fold the time the AChR spends in the open state, explaining how nerve cell excitation would increase and trigger a seizure. We also found that the mutation of the receptor occurs at a region that modulates function. After pinpointing the molecular regions of the receptor responsible for the open-to-close transitions, we modified the regions and successfully mitigated the enhanced activation. We also identified a region that tunes receptor opening and closing through specific properties of amino acid residues. Collectively, the findings pave the way for targeted therapies against sleep-related epilepsy disease.

How did Mayo help you grow as a scientist and as a thinker?

As a Ph.D. student, you become an expert learner — and you realize there's a lot out there that you don't yet know! Mayo helped me grow as a critical thinker. I especially appreciated the discussion-based courses in the first years of grad school. Some classes incorporate journal clubs that involve dissecting a research article, asking questions such as: What additional experiments could have been done to support the work, or what new hypotheses could be generated from the findings? Conducting research at Mayo is special. The collaborative culture between the medical and research fields reminds you to always consider the significance of your work in solving current or future biomedical challenges.

What motivates you?

I am passionate about problem-solving and love the discovery part of science. Those first few moments when you are the first person to know something new are very exciting. My ultimate goal is to apply myself toward improving people's health through contributions in medical and pharmaceutical sciences.