Foster Lab tests DNA mutations

Eleven years ago, microbiologist Patricia Foster came to IU hoping to be involved in an undergraduate educational setting and an environment of diverse research efforts.

Since then, it seems she has found exactly what she was looking for, and perhaps more, as her research continues to result in publication and recognition.

In 2008, Foster was honored as a fellow of the American Academy of Microbiology, which recognized her for her work on mutagenesis of Escherichia coli (E. coli).

Today, Foster continues to examine stress-induced mutagenesis in her lab in Simon Hall, now with three graduate students, one research associate and one undergraduate student working on different sides of the investigation.

The students play an integral role in executing the research — especially because Foster is spending the summer and fall in Cambridge, England, on sabbatical.

“We keep in touch with Pat via e-mail and weekly Skype meetings,” said Kyle Hetrick, a graduate student in the Foster Lab. “She oversees all of the work that we do.”

The general focus of the lab is the complex relationships among stress responses that organisms encounter in their environment. In this case, the model organism is E. coli, but the larger-scale implications of the research indicate that it could further a general understanding of how various stresses affect prokaryotic mutagenesis, leading to a better understanding of microbial genetics overall. This is important for medical applications because a number of human pathogens are bacterial.

The primary research topic is attacked from a variety of angles, with different projects occurring simultaneously in the lab.

“As a graduate student, I study a facet of the larger picture,” Hetrick said. “I look at nutritional stress and its effects on a specialized DNA polymerase in E. coli.”

More specifically, Hetrick studies E. coli cultivated in phosphate-deficient environments and examines how the nutritional stress affects DNA Polymerase IV activity.

While DNA Polymerases I, II and III are known to replicate DNA with a high level of accuracy, DNA Polymerases IV and V tend to work with higher rates of inaccuracy, leading to changes in the DNA. Because Foster and her colleagues are interested in mutation rates in E. coli, DNA Polymerase IV serves as a good focal point for such studies.

“I have been mostly interested in a class of enzymes that copy the genetic material, DNA, but do it badly,” Foster said in an e-mail. “They make mistakes, which result in mutations. We have been generating evidence that the mutagenic activities of these enzymes get turned on and off, and I would like to understand the molecular basis of this regulation.”

As the lab continues to work on these different projects, the team collectively faces successes and failures on a daily basis.

“Failure is a very common part of groundbreaking research,” Hetrick said. “You never know what’s going to happen in the lab.”

Thanks to a lot of hard work, however, the Foster lab has recently experienced great success.

On June 16, the Department of Defense announced its intent to award an estimated $227 million in grants to research institutions as a part of its Multidisciplinary University Research Initiative.

IU was among the 32 universities honored with this award for a collaborative effort led by Foster.

The proposed five-year grant will fund a completely new project, involving the collaboration of the Foster Lab with Mike Lynch, a professor of biology associated with the School of Informatics; Haixu Tang, director of bioinformatics at the Center for Genomics and Bioinformatics at IU; and Steven Finkel, a colleague of Foster’s at the University of Southern California.

“The general idea (of this research) will be to take a genome-wide view of what’s happening with mutagenesis, starting with E. coli,” Hetrick said while describing the excitement surrounding the award in the lab.

This is important because the current understanding of these principles is limited to knowledge of what happens in small, specific regions of the genome.

With the inter-departmental collaboration effort that this grant will provide for, the concepts can be studied on a much larger scale.

The Foster Lab will cultivate the strains of E. coli to be studied, the Center for Genomics and Bioinformatics will sequence the DNA of the organisms using Illumina technology and the bioinformatics groups will work to sort and interpret the data, pointing out areas of potential interest for further research.

“The practical application of this research, as far as the Department of Defense is concerned, is forensic,” Foster said in the e-mail. “They are interested in defining mutational signatures (that) may help to identify the source of a bacterium, be it a naturally occurring disease organism or a bioterrorism agent.”