Isabelle Baconguis graduated from the University of Pennsylvania with a B.A. in Biochemistry.  She remained at PENN for two years studying glutamate receptors. Interested in ion channel physiology, she joined the Neuroscience Graduate Program at OHSU and joined Dr. Eric Gouaux’s lab in the Vollum Institute. During her doctoral research at the Vollum Institute, she studied acid sensing ion channels (ASICs), members of the superfamily of amiloride-sensitive and Na⁺-selective trimeric ion channels. Using a combination of x-ray crystallography and electrophysiology, she exploited toxin-dependent modulation of ASIC function to elaborate molecular mechanisms of gating, selectivity and ion channel block. As a recipient of the NIH Director’s Early Independence Award, part of High-Risk High-Reward Program, Isabelle skipped postdoctoral training to immediately pursue her research program of understanding water and salt balance using structural techniques initially focusing on the epithelial sodium channels (ENaC). She joined the Vollum Institute as the inaugural Vollum fellow in 2013 and was promoted to assistant scientist in 2016.

Insights into the function of trimeric Na⁺-selective ion channels

My group studies an ion channel superfamily in which members share a common architecture but exhibit diverse functions, the Epithelial sodium channel (ENaC)/Degenerin (DEG) channels. Here we focus our efforts on ENaC using a combination of single-particle cryo-electron microscopy and electrophysiology to define the molecular basis of heteromeric assembly and gating of two ENaC complexes: abg and dbg. We find that ENaC arranges in a preferred counterclockwise configuration to form a stable trimeric assembly. In addition, we identified regions in the extracellular domains of the a and d subunits that may participate in the binding of cations that mediate inhibition and activation of abg anddbg channels, respectively. Together, our findings highlight the importance of diverse subunit compositions in fine-tuning ion channel properties.

This event is supported by the Thomas Dunne Lecture Fund.