Interdisciplinary Initiatives Program Round 7 - 2014

Merritt Maduke, Molecular & Cellular Physiology
Justin Du Bois, Chemistry
Ben Barres, Neurobiology, Developmental Biology
John Huguenard, Neurology
Vijay Pande, Chemistry

The careful regulation of Cl– ion concentrations is critical to the proper functioning of the brain . We are interested in understanding the role of specific Cl– ion channels (CLCs), large proteins that enable transport of Cl– across cellular membranes, for electrical conduction and homeostasis in brain cells and how these proteins become malfunctional in brain disorders such as epilepsy and leukodystrophy (degeneraton of white matter). Molecular design and computational chemistry, chemical synthesis, and molecular biology make possible access to potent and selective reagents for modulating Cl– channel activity. These chemical ‘tools’ will be used to validate specific hypotheses that link aberrant CLC function to improper signaling within the brain. Our investigations should lead to the identification of CLCs as protein targets for neuropharmaceutical research and new small-molecule therapeutic lead compounds for treatment of neurological disease.