For more than a decade, Assistant Professor Richard McKenney, Department of Molecular and Cellular Biology, has dedicated his research to the microscopic world of movement and transportation within cells.

Now, a two-year, $150,000 research award from the March of Dimes will support his research to better understand how molecular dysfunction influences prenatal brain development.

With the Basil O’Connor Starter Scholar Research Award, McKenney will continue to study the genetic mutations that lead to lissencephaly, a condition where the brain is smooth rather than folded, and microcephaly, in which the brain is smaller than usual. 

“We want to use our expertise in studying individual molecules to try to understand how they work,” McKenney said. “If we can start laying the foundation for understanding what goes wrong, maybe, in the future, we can make some progress and alleviate some of these conditions.”

It all starts with cell division

McKenney’s research will focus on molecules that interact with, and regulate the motor protein dynein. Dynein’s activity is essential to many basic cellular processes including cell division and cell migration.

He is especially interested in genes LIS1 and NDE1, which direct the proteins that interact with dynein. Mutations in these genes are known to negatively impact human prenatal brain development.

McKenney believes that both LIS1 and NDE1 play an important role in dynein’s motor function, and, as a result, the cell’s ability to perform important processes such as cell division. Previous research from McKenney’s lab demonstrated that dynein’s motor activity is key to the formation of the mitotic spindle, which is necessary for cell division. He wants to determine how these dynein regulatory proteins affect the motor’s ability to perform such an important task. 

“If those roles are disrupted, then cells in the brain cannot go through mitosis normally,” McKenney said. “Without this ability, you get fewer cells, which can lead to smaller and smoother brains.”  

McKenney also wants to study a third protein called DCX. Though not a motor protein like dynein, DCX binds to microtubules, and DCX mutations have been linked to a form of lissencephaly. He believes that DCX may regulate dynein’s motor activity along microtubules in a way that is critical for brain development.

Emphasizing foundational research

McKenney’s lab will investigate these biological phenomena using a technique called single-molecule microscopy. The technique allows researchers to observe molecular processes outside of living cells.  

For McKenney, the research award is somewhat of a homecoming because he started his research career investigating LIS1 and dynein. He’s grateful the March of Dimes organization recognizes the importance of funding foundational research.

“In my opinion, we’re working fairly far away from patients and even model systems that mimic the diseases,” he said. “I’m very happy the March of Dimes was willing and enthusiastic to fund basic research, which is needed before we can try to treat the disease.”