Advancing research on how cells grow, organize, and bind

June 26, 2017

An Indiana University microbiologist has received a five-year, $4 million award from the National Institutes of Health to advance research on bacterial cell biology.

Yves Brun, IU Distinguished Professor and Clyde Culbertson Professor in the IU Bloomington College of Arts and Sciences’ Department of Biology, has been awarded the NIH’s Maximizing Investigators’ Research Award, or MIRA. The grant is part of the National Institute of General Medical Sciences’ Outstanding Investigator Award Program.

“Bacteria affect people in many ways — both beneficial and harmful — in areas such as health, agriculture, industry and environmental sustainability,” said Clay Fuqua, professor and chair of the Department of Biology. “Yves’ work is at the forefront of research on bacterial development, shape, growth, internal and external cellular organization, and emergent properties such as biofilm formation. This grant is an important recognition of these efforts and will catalyze continued groundbreaking work from his lab.”

MIRA grants are designed to provide greater stability and flexibility to NIH-funded investigators who have outstanding records of productivity and innovation, with less time spent on grant applications and more hours in the laboratory. This stability also encourages more ambitious, longer-term research projects with higher probability of breakthrough discoveries.

Brun’s award will fund research on three major topics: how bacteria grow and reproduce; how their cells are organized; and how they bind to surfaces.

“The specific location of proteins inside bacterial cells — and how they coordinate with one another — drive many important and complex processes in bacteria,” Brun said. “This includes the synthesis of compounds that control cell elongation and cell division; the differentiation of bacterial cells into specialized cell types; the synthesis of cell surface structures; the adhesion of bacterial cells to surfaces; the formation of ‘biofilms’; and cellular aging.”

A major area of Brun’s research concerns how bacterial cells synthesize a compound called peptidoglycan, a compound of sugars and amino acids that make up cell walls. The award from the NIH will support the development of innovative new methods to physically track the coordination of bacterial cell structures in real-time as they build these walls.

The grant will also support research into bacterial cellular organization, especially how certain proteins cluster at certain sites within bacterial cells to drive growth and the formation of specific structures. Brun plans to focus particularly on “scaffolding” proteins in the bacterium Caulobacter crescentus and related species, with the goal of increasing knowledge on how to slow or cease bacterial growth.

The final area of investigation under the grant is the biological mechanisms behind bacterial adhesion, the process that enables bacteria to attach to surfaces. This work aims to help address the need for new biomedical adhesives, which are increasingly used in dental, bone and tissue surgery. Adhesives also play an important role in industries such as electronics, power and engineering.

In general, Brun notes that research on cellular structures and growth also informs the development of new drugs in the fight against antibiotic resistant bacteria. These bacteria are estimated to cause 1 in 4 hospital-acquired infections in the United States, according to the Centers for Disease Control and Prevention. Over 700,000 of these infections, including 75,000 deaths, were recorded in 2011.

“We’ve been studying these critical processes in bacteria for many years under support from NIH, and we find that the common themes that underlie them are striking,” Brun said. “This award unites these major themes together under a single umbrella. We’re looking forward to new discoveries and advances enabled by this support.”