Jianhua Zhao secures a $2.4 million NIGMS grant to study the molecular machinery of proteolysis

Assistant Professor Jianhua Zhao, Ph.D., was awarded a unique and competitive fellowship by the National Institute of General Medical Sciences (NIGMS), a part of the National Institutes of Health (NIH). The five-year, $2.4 million grant aims to give researchers greater research flexibility to work on fundamental questions in biology.

“This award alleviates the need to constantly write new grants, giving us more time and space to devote to actual research,” says Zhao. “This is an emerging financing model that has gained a lot of popularity recently.”

The grant was awarded through NIGMS’ MIRA program, which stands for Maximizing Investigators’ Research Award. While most NIH grants fund individual projects, with specific results identified for each grant, this new funding program distributes funds to researchers to fund multiple ongoing projects simultaneously.

Science is never linear. The results of an experiment always inspire new questions, and this grant allows us to follow those threads as they arise.”

Jianhua Zhao, Ph.D., Assistant Professor

Zhao’s research focuses on proteolysis, the process by which cells break down and recycle unused proteins. Proteolysis is essential for normal cell replication, as our cells use the byproducts of this process to know when it’s time to replicate. Because cancer develops when cellular replication gets out of hand, proteolysis is also an important process for cancer cells.

“Disrupting protein recycling is already an established therapeutic strategy for some types of cancer, such as multiple myeloma,” says Zhao. “Our goal with this grant is to learn more about the fundamental biology of this process and the structures that control it, so that we can open up new avenues for cancer treatment.”

To study the molecular machinery of proteolysis, Zhao and his team will use a state-of-the-art imaging approach for proteosomes, the multi-protein structures that control proteolysis. The method, called cryo-electron microscopy (cryo-EM), works by lowering samples to extremely cold temperatures, making it easier to generate atomic-resolution images of biological molecules.

“Cryo-EM is extremely high-resolution, much higher than other imaging methods,” says Zhao. “The ability to apply it to biomolecules is a major advance in methodology that is changing the landscape of structural biology.”

Another advantage of the approach is that it requires very little sample, which means it can be used to study proteins that are present in very small amounts in our cells.

“This is important because it brings us closer to seeing what biological molecules actually look like when they’re inside our cells,” says Zhao. “We look forward to unlocking the potential of this method and using it against cancer.”