Gabriel C. Lander
Understanding Macromolecular Structure and Function with CryoEM
Neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Lou Gehrig’s, and Huntington’s, affect more than 6 million people in the U.S., yet treatment of these diseases remains limited to a relatively small set of therapies that only mitigate the effects of the disease, rather than to inhibit or modify its progression. This absence of targeted therapies partly stems from the fact that our molecular understanding of the fundamental events that trigger the onset of these diseases is severely limited. Using high-resolution 3D imaging, we plan to determine the precise neuronal mechanisms that are involved in maintaining neuronal integrity. By determining the structures of the machinery involved in these processes, we will gain substantial insight into the molecular relationships that give rise to normal neuronal function, which is the first step in understanding progression of neurological disease. Specifically, my lab is investigating the underlying mechanisms by which small molecular motors are responsible for transport of nutrients within neurons. Importantly, these motors are involved in clearing away the dangerous protein aggregates that are associated with a large number of neurodegenerative diseases. Using high-resolution cryo-electron microscopy, we hope to outline the interplay between molecular motors and microtubules, and pinpoint events that lead to the manifestation of neurodegeneration. Importantly, these studies will provide the critical structural data that could one day deliver new avenues to treat these diseases.