NIH Grant Supports the Study of Molecular Motors to Understand Brain Disease

brain disease
A $1.37 million study conducted by William Hancock, professor of biomedical engineering, funded by the National Institutes of Health Institute of General Medical Sciences, will support the investigation of intracellular transport and cell division to better understand the molecular basis of neurodegenerative diseases. Image: © iStock/Eraxion

A National Institutes of Health (NIH) Institute of General Medical Sciences grant will support the study of intracellular transport and cell division to better understand the molecular basis of neurodegenerative diseases.

The $1.37 million award will support the proposal, “Molecular Mechanism of Kinesin Motility,” which aims to explore the ways kinesin motor proteins — a family of motor proteins found in all multicellular organisms — move throughout cells to transport biological cargo, and the impact they have on cell division.

“Kinesin motor proteins are involved in both the transport of cargo inside of cells and the creation of new cells through cell division,” said William Hancock, professor of biomedical engineering, Penn State. “Our research aims to identify the mechanistic framework that defines how various kinesin motor proteins are responsible for each of these actions.”

There are 45 unique motor proteins within the kinesin family, which travel along microtubule tracks in the body to deliver important cargo such as proteins, vesicles and other components that make up cells. While it is known that defects and interruptions in kinesin transport processes may lead to the development of neurodegenerative diseases, it is still largely unknown how different kinesin motor proteins can affect this behavior, and the properties that make each of the motors unique.

To analyze individual kinesin proteins, researchers will use a powerful new microscope to examine how they walk along their microtubule tracks. Built in Hancock’s lab, the microscope features a spatial resolution of two nanometers and a temporal resolution better than one millisecond. The new technology will allow researchers to track the substeps of the kinesin motor proteins to evaluate their behavior in ways that have not yet been observed under standard physiological conditions.

The findings, combined with a series of biochemical measurements and computational modeling simulations developed by the research group, will allow the team to draw new conclusions about the inner workings of the molecular motors.

“We are hopeful that an increased knowledge of kinesin motor proteins may lead to a better understanding to the development processes of many widespread neurodegenerative diseases,” said Hancock.  “Likewise, understanding the role kinesin proteins play in cell division may further help us to develop anti-cancer therapies to stop undesirable cell growth in tumors.”

The grant supports a four-year research study that expands upon previous research, also supported by the NIH, aimed to uncover the ways different kinesin motor proteins can be optimized for various cellular tasks.