Researchers use cryo-EM to identify what makes bacteria strong

In 2019, , the James K. Billman Endowed Assistant Professor in the , delivered a research talk that set the stage for a collaborative breakthrough that was decades in the making. In the lecture hall that day was Professor Emeritus Lee Kroos, who has now recently retired from MSU after a pioneering career of over 30 years.

Kroos had long worked with Spartan colleagues to capture the elusive structure inside a protein known as SpoIVFB (pronounced "spo-four-eff-bee"). SpoIVFB belongs to a family of specialized enzymes. These enzymes help regulate key cellular functions across all kingdoms of life.

SpoIVFB plays a critical role in sporulation -- a process that allows bacteria to withstand extreme environments.

With attempts to capture SpoIVFB's structure proving challenging over the years, Kroos was interested to learn of Orlando's expertise in the cutting-edge field of cryogenic electron microscopy, or cryo-EM.

"Cryo-EM allows us to peer into a world that we simply can't see through any other lens," said Orlando.

Now, in a appearing in Nature Communications, the Orlando and Kroos research groups report the first high-resolution experimentally determined structures of SpoIVFB.

Specifically, the researchers have revealed SpoIVFB is bound to the particular molecules that it interacts with, facilitating the creation of useful biochemical products.

This study offers insight into a mechanism of cellular regulation found in organisms ranging from bacteria to humans, with exciting implications for microbiology, structural biology, enzymology and human disease.

The breakthrough is also a testament to the ongoing $15 million expansion of advanced cryo-EM infrastructure at MSU that continues to allow Spartan researchers to push the boundaries of experimental feasibility.

"Over the last several years, this technology has been transformative in membrane protein structural biology," said Orlando, who was recruited by MSU as part of its Global Impact Initiative -- a campuswide undertaking that seeks to tackle grand challenges in energy, health, education and the environment.

These findings contribute critical knowledge to structural biology, as well as links to neurodegenerative diseases, cancers and metabolic disorders.

By taking thousands or sometimes millions of images of a sample at different angles, researchers can create a highly detailed 3D map of the sample that is being imaged.

"This technology helped get us over that mountain and, as it improves, we'll peer deeper and deeper into new areas of biology," said Orlando, who looks forward to what the expansion of MSU's cryo-EM facility will mean for researchers working across an array of disciplines, from materials science to microbiology and biochemistry.