Scientist at Work: Patricia Foster
For most people, the word mutation is evocative. It conjures up the heartbreak of cancer, the specter of super viruses and even science fiction movie monstrosities.
But mutations aren't all bad. They occur naturally in the genomes of all organisms and many are harmless or even beneficial, says Indiana University Bloomington biologist Patricia Foster, who is a widely esteemed expert on mutation in bacteria.
Despite over a century of research, Foster says many of the processes behind DNA mutation remain mysterious. She and colleagues at IU Bloomington and the University of Southern California, however, are providing new insights into this complex natural phenomenon.
A mutation is a heritable change in the genome of a living organism. Mutations can be caused by mistakes during cell division or DNA replication and when the DNA is repaired.
Environmental factors can play a role in mutation, too, either by directly changing DNA (for example, through radiation damage or interaction with carcinogenic chemicals), or indirectly, by inducing an organism to alter its own mutation rates, a strategy that Foster says can influence the chance that an individual or its progeny will survive harsh times.
Up to now, Foster says there has been no experimental model that adequately predicts how environment affects genetic mutation. But Foster is helping to develop one.
"These experiments we are starting to carry out are among the first of their kind," says Foster, who is principal investigator of the IU Bloomington-USC project. "Using the bacterium E. coli, we will investigate how the types of mutations that arise can be diagnostic of the environment to which the microorganism has been exposed both in short and long evolutionary periods."
The team of researchers will expose Escherichia coli, a model species that is commonly found in mammalian digestive tracts, to different kinds of environments and allow the bacteria to reproduce for 150,000 generations. Over time, the bacteria will slowly accumulate mutations in their genomes, which the researchers hope will provide answers as to how environment influences mutation rates -- as well as the types of mutations the organisms incur. Bacteria that have lost the ability to repair different types of DNA damage will also be tested to determine how important DNA repair is to the accumulation of mutations. Similar experiments will be performed in other bacterial species to see if the conclusions are universal.
Previous work by Foster has focused on short term experiments examining an organism's ability to keep its genome stable.
"I have long been interested in understanding the conflict between accurate replication of an organism's genome to retain the genetic content of a species and the need for new genetic variants to ensure the ability to evolve if the environment changes," says Foster.
It makes logical sense then for Foster to carry over her research interests investigating how environment affects a genome in long-term experiments. She hopes this work will tell the full story of environment's role in genetic mutation. To ensure that all important aspects are being covered, Foster has assembled a unique team to provide a comprehensive analysis of this research.
"I am very excited about these experiments," Foster says. "I will be working with colleagues who are modelers and informaticists, which will be a new experience for me. I have wanted a more mathematical framework for analyzing mutation rates and changes for a long time, and this is finally coming about."
One goal of the research is to determine what kinds of mutations naturally occur and at what rate they are appear. Another goal is to develop a new model for predicting how environment will affect the genetic composition of microorganisms that will contribute to the overall understanding of genomic instability in bacteria. To do this, the collaborative team will take advantage of recent technological advances in genome sequencing to see the entire genomes of the E. coli and the other bacteria in each environment.
"The technical ability to do this is breathtaking, and I am very excited about learning how to do it," says Foster.
Foster's collaborators on the project are USC molecular geneticist Steven Finkel, IU Bloomington evolutionary biologist Michael Lynch, and IU Bloomington bioinformaticist Haixu Tang.
This research is just getting underway but Foster is already considering how the outcomes might affect research in her field.
"Our overall goal is to establish baseline parameters, achieve mechanistic understanding, and develop predictive models that will yield a comprehensive understanding of the forces that ultimately define short-term and long-term patterns of microbial molecular evolution," Foster says.
Foster's research is being funded by grants from the U.S. Army Research Office, part of the U.S. Department of Defense Multidisciplinary University Research Initiative program.