Merritt Maduke
Stanford University
Biophysical Journal Editor, Channels, Transporters, and Receptors
What are you currently working on that excites you?
In general, I love it when a student or postdoc discovers something I had not envisioned. This happened with Anna Koster, a recently graduated chemistry PhD student who wanted to develop small-molecule tools for studying the CLC-2 voltage-gated chloride channel. CLC-2 is expressed broadly in the central nervous system, but in contrast to the potassium, sodium, and calcium-selective voltage-gated channels, little is known about how it contributes to brain function. I told Anna that while it would be great to have a specific small-molecule CLC-2 inhibitor, it wouldn’t be a good thesis project because I didn’t have any good ideas on how to succeed. Fortunately, Anna persisted. Starting with a low-micromolar “hit” compound identified in a small screen, Anna conducted a methodical study of structure-function relationships and developed a novel compound with 17 nM potency against CLC-2 and >1000-fold selectivity over other chloride channels. This project, initiated and driven by Anna, has been a rewarding collaboration between colleagues in chemistry, neurology, and computer science (Justin Du Bois, John Huguenard, and Ron Dror laboratories). We are currently following up on Anna’s work by performing biophysical studies to understand the molecular basis for the inhibitor specificity and physiological studies to investigate CLC-2 function in the brain.
At a cocktail party of non-scientists, how would you explain what you do?
My postdoc mentor used to joke that the science we are interested in is so nerdy that its main benefit to society is that it keeps us off the street. While I am a proud card-carrying nerd, I am also passionate about the value to society of the nerdy details illuminated by our research. At a cocktail party (when invited), I like to proclaim that every biomedical breakthrough of the past century was made possible by the hard work of nerdy scientists who just wanted to understand how the world works. When I explain that I am interested in how humans and other animals generate electrical signals, I find that most people are also truly curious about these things. It is so energizing!