Baltimore, MD — Due to the critical nature of ribosomal quality to human health, Carnegie postdoctoral researcher Zachary Stolp seeks to define the poorly-understood quality control mechanisms that mammalian cells impart on ribosomal RNA (rRNA). The National Institutes of Health has recognized Stolp's efforts, awarding him with its prestigious Ruth L. Kirschstein National Research Service Award.

Ribosomes, complex molecular machines found within all cells, play an essential role in translating genetic code into proteins — making them one of the most vital components of life. As with all complex machines, ribosomes can “break down,” leading to a wide range of diseases, including cancer and neurodegeneration. Cells need to maintain the integrity of ribosomes in order to ensure faithful protein production, but due to technological constraints, researchers know little about how this happens.

“A lot of what the field has studied thus far is focused on quality control when other translational components are damaged or misformed, such as the messenger RNA or newly-made protein,” says Stolp. “But no one focuses on when the ribosome itself — or part of the ribosome, such as rRNA, is damaged.”

 

Zachary Stolp handling cells expressing mutant ribosomal RNA.

 

As a member of the Kostova Lab at Carnegie’s Department of Embryology, Stolp has engineered a fluorescent rRNA reporter for genetic screenings to elucidate the molecular pathways of ribosomal quality control.

“We can express the fluorescently tagged rRNA in cells and then break it, rendering the ribosome non-functional to see how the cells react,” explains Stolp.

By pairing his unique method with other cutting-edge tools such as CRISPR-mediated genome editing, Stolp hopes to determine how human cells cope with defective ribosomes — and to provide the foundation for understanding how dysregulation of this process leads to human disease.


Visit kostovalab.org to learn more about Carnegie's ribosome research.