Study to identify functions of hypothetical genes in two infectious disease pathogens

Sean Crosson, PhD, associate professor of biochemistry and molecular biophysics will lead the effort to characterize hypothetical genes -- genes revealed via genome sequencing that as yet have no defined functional role -- as part of a new Functional Genomics program at the NIAID. These studies will be carried out in collaboration with Olaf Schneewind, MD, PhD, professor and chair of the Department of Microbiology.

A total of 102 genes encoding proteins and small regulatory RNA sequences in the bacteria Yersinia pestis, which causes plague, and Brucella abortus, which causes brucellosis, a livestock disease that can be transmitted to humans, will be investigated. Targets were selected based on preliminary studies by the Crosson and Schneewind research groups that indicated potential roles for these genes in infection. This research program will be centered at the Howard Taylor Ricketts Laboratory, a level 3 biocontainment facility housed on the campus of Argonne National Laboratory that was constructed in partnership between the NIH and The University of Chicago.

"We have an opportunity to study genes that no one has ever studied," Crosson said. "Assigning function to hypothetical genes can inform studies of all species that contain similar genes."

The University of Chicago researchers are particularly interested in better understanding how these hypothetical genes are related to the infection process. Both Y. pestis and B. abortus are transmitted to humans through animals, and gaining insight into the biological mechanisms for infection could have implications for human health and even bioterrorism.

"This information is very valuable to the infectious disease research community. Right now, researchers that encounter these genes in their genetic screens or expression experiments don't know what to do with them," Crosson said.

Together with collaborators from Argonne National Lab, this research team will use cross-disciplinary bioinformatic, biochemical and genetic approaches, and animal infection models, including fleas, to define gene function. In addition, they will utilize structural biology resources such as the Advanced Photon Source at Argonne to study the biochemical functions of proteins encoded by hypothetical genes.

"This project leverages many of the strengths of The University of Chicago and Argonne. We're a group of experimental biologists, biophysicicts, chemists and bioinformaticians coming together to expand our knowledge of microbial gene function," Crosson said.