New faculty member broadens U-M’s structural biology expertise

October 28, 2020

Shyamal Mosalaganti, Ph.D.

Human cells — like all eukaryotic cells — contain more than a dozen types of membrane-encapsulated compartments called organelles. These are in constant motion and communication within the cell, to perform their essential roles in maintaining cell growth and health.

“If we truly want to understand how these organelles function — how they move, how they send and receive signals — we have to be able to view their components in high detail, within their cellular environment,” says Shyamal Mosalaganti, Ph.D., who just began a faculty position as an assistant professor at the University of Michigan Life Sciences Institute.

Mosalaganti’s new research program at U-M will take advantage of the LSI’s cutting-edge cryo-electron tomography (cryo-ET) resources to do just that.

The most common structural biology approaches have relied on isolating cellular components and visualizing them in purified form. But, Mosalaganti explains, those techniques remove the complexes from the context of the cell. For cryo-ET, however, cells are flash-frozen, and then imaged with an electron microscope to reveal their native inner workings.

This approach bridges the gap between structural and cell biology by enabling scientists to determine structures directly inside the cell, explains Mosalaganti, who is also an assistant professor of cell and developmental biology at the U-M Medical School.

“If you think of these cellular complexes as the engine of a car, for example, traditional structural biology let us visualize all of the parts of the engine in great detail, and cryo-electron microscopy let us see the assembled engine,” he explains. “Cryo-ET now lets us see the complete engine within the context of the car, interacting with other components of the machine.”

Mosalaganti comes to the LSI from a postdoctoral research fellowship at the European Molecular Biology Laboratory, Germany, where he used cryo-ET to study the largest cellular complex that allows molecules to flow between the nucleus and the rest of the cell.

At the LSI, he will apply his cryo-ET expertise to investigate a type of organelle called lysosomes, which not only play an important role in cellular 'waste management,' but also serve as a key decision-making center controlling cellular growth and survival. Mosalaganti will examine how these organelles move and communicate with other organelles in the cell — and how their functions, and loss of these functions, affect human health and disease. 

This combination of structural and cellular biology is a perfect fit for the collaborative, multidisciplinary research environment of the LSI and adds a new dimension to the institute’s state-of-the-art structural biology program, says Director Roger Cone, Ph.D.

“We are thrilled about all that Dr. Mosalaganti will bring to the LSI and the university,” Cone says. “His expertise in this tremendously exciting new area will enable the LSI to continue advancing the power of structural biology to make paradigm-shifting discoveries in the life sciences.”  

The LSI is home to the Center for Structural Biology, a core lab that specializes in X-ray crystallography and protein production, and to the Cryo-Electron Microscopy Lab. The institute’s recent expansion into cryo-ET, including the addition of Mosalaganti to the faculty, was supported by the U-M Biosciences Initiative.