From Bacteria to Biofuels: Understanding Cellular Survival
MARY DUNLOP, PH.D., ASSISTANT PROFESSOR OF COMPUTER SCIENCE
Mary Dunlop, Ph.D., is looking into how organisms respond to changing environments, and in doing so, she's crossing disciplines, using synthetic and systems biology to research natural and manufactured cellular processes. Dunlop, assistant professor in the School of Engineering and associate faculty member in the Vermont Complex Systems Center, was the recipient of the National Science Foundation's CAREER Award, the Outstanding Junior Faculty Award from UVM's College of Engineering and Mathematical Sciences, and the U.S. Department of Energy's Early Career Award. She's interested in studying how microscopic organisms — bacteria — handle macroscopic phenomena — antibiotic resistance and biofuel production.
"My lab takes two different perspectives," says Dunlop. "One is trying to understand natural examples of how cells can deal with changing environments. The other is exactly the opposite direction, where we try to build completely novel feedback systems that don't exist in nature."
That work begins with the basic knowledge that bacteria, though single-celled, have a complexity and a level of individuality that renders them useful models of more intricate biological systems. Through studying E. coli, Dunlop and her team of five graduate students and one undergraduate have found that even cells that are genetically identical can take on different phenotypes, or characteristics, allowing them to "hedge against uncertainties in the future." That may translate to a microbe's ability to evade antibiotics, for example, by turning on an efflux pump that will force the drugs away or at the very least make the organism more tolerant of them; another reaction might be a change in its cell membrane composition. Regardless of the response, if it were shared by an entire colony that could be costly — especially if there's little likelihood of an antibiotic encounter. Instead, such a task is generally relegated to a smaller subset of the population, which, says Dunlop, serves as an insurance policy. That way, if something were to happen to the responsive subgroup, the surviving cells would still be able to regenerate. Although she and her colleagues focus on E. coli, the mechanisms are common to a variety of different microbes, Dunlop says, including pathogens.
Their research is focused on why the changes happen, but Dunlop says it's not impossible that one outcome down the road would be a finding that when cells diversify their responses, they trade off which cells in a given population are antibiotic resistant and for how long. That may be important from a clinical perspective because knowing how long that transient resistance lasts may affect length of treatment. For the most part, however, they remain focused on costs and benefits of the different cellular approaches to survival — that bet hedging within the cells: some might survive while others do not, but even so they have collectively diversified their responses. Dunlop uses time-lapse microscopy — basic time-lapse photography under a microscope — with fluorescent colors to assess changes and establish quantitative histories of the cells over time.
On a somewhat larger scale, Dunlop's lab is researching the creation of transportation biofuels from cellulosic — plant-matter — sources. While most biofuel is currently made from corn and sugar cane, Dunlop is looking at the end process of converting recycled material — debris from forests, grass clippings, and the like. Likening it to making beer, in which the level of alcohol is naturally self-limiting to avoid yeast die-off, Dunlop says cells that are converted to biofuels suffer from the same toxicity concerns.
"That's a real problem for making biofuel," says Dunlop. "You want to make a lot of fuel to be efficient and cost effective, but after a certain point, the cells start to die." In an effort to make microbes more robust, Dunlop is studying their tolerance mechanisms, using organisms that exist in harsh environments, such as areas around natural oil seepages in the ocean, or near oil rigs or spills. Such microbes, whose primary purpose is to eat hydrocarbons, have developed a tolerance to high quantities of biofuel-like compounds; Dunlop hopes to find which genes are responsible and eventually crossbreed them with E. coli to create a more durable cell.
Last modified May 19 2014 04:01 PM