Federal Project Grant Award Summary

Northwestern University's Sponsored Research Division received a $630,651 Project Grant from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853), effective June 1, 2026 through May 31, 2031. The research focuses on elucidating the molecular mechanism of magnesium transport in neuronal homeostasis, specifically investigating the structure and transport mechanisms of the CNNM (Cyclin and CBS Domain Magnesium Transport Mediator) family of membrane proteins. These proteins are critical for maintaining cellular magnesium balance and neuronal signaling; dysfunction is associated with neurological disorders including epilepsy, developmental delay, and neurodegeneration.

The project integrates high-resolution cryo-electron microscopy with biochemical and functional assays to define how CNNM proteins recognize magnesium-ATP, undergo conformational changes to mediate magnesium efflux, and sense intracellular magnesium levels. The research will also investigate how allosteric regulators, including small-molecule compounds and regulatory proteins such as PRLs (phosphatases of regenerating liver) and ARL15 (ADP-ribosylation factor-like GTPase 15), alter transporter structure and function at the molecular level. This fundamental research addresses significant gaps in understanding magnesium transport mechanisms central to nervous system health and may inform therapeutic strategies for magnesium-related neurological disorders.