Georgetown College. Georgetown University.

By Megan Weintraub

In describing a particularly perplexing area of her current research, Dr. Anne Rosenwald, a professor of Biology at Georgetown, recalls the famous anecdote in which six blind men attempt to determine the identity of an animal by each touching one of its distinct parts. Ultimately, the men are unable to discern that the animal is an elephant because they lack a holistic view of its shape.

“Often, research yields exciting clues for how to solve part of the puzzle, but it can take some time to piece it all together,” explains Dr. Rosenwald. “Finding ways to bring together different strands of research motivates me in the lab.”

Dr. Rosenwald’s research looks at Saccharomyces cerevisiae (commonly known as baker’s yeast) because it is a model organism for cell behavior in humans. In her experiments, she mutates the genes of Saccharomyces cerevisiae in order to identify protein function in cellular membrane traffic. By manipulating particular genes, she is able to reveal various aspects of a cell’s reaction to stresses in its environment.

In order to function properly, cells use the equivalent of traffic cops to direct molecules like proteins and lipids to the right place so that they can perform their designated task. In her studies of membrane traffic, Dr. Rosenwald researches these regulators of cellular movement. Similar to the genetics work of Dr. Ronda Rolfes, Dr. Rosenwald’s research draws from molecular biology, genetics, and cell biology. While Dr. Rolfes studies how genes turn on and off in the yeast, Dr. Rosenwald is interested in how the proteins that are encoded by the genes end up in the right place in the cell. Dr. Rosenwald’s two main areas of study—molecular switches and the role of potassium in cellular function—focus on the processes that enable a smooth flow of cellular membrane traffic.

“Membrane traffic relies on the efficient functioning of a cell’s molecular switches, states of being within the cell that dictate how various components should behave,” explains Dr. Rosenwald, whose work is funded through a National Science Foundation grant. “In all eukaryotic (nucleated) cells, proteins that work as the molecular switches turn on and off several important processes, like cell growth and division, but we’re most interested in the switches that regulate traffic.”

Dr. Rosenwald seeks to identify the ways in which specific proteins facilitate or inhibit molecular switches. Recently, her research has honed in on two proteins called Arl1 and Mon2. Arl1 is the switch protein, and Mon2 mediates whether Arl1 is on or off.

“Arl1 is one member of the Arf-like family of proteins, a protein family that is well-conserved across eukaryotic evolution. Because these proteins are found in all eukaryotes examined thus far, we’re sure they’re important for cellular function, but not much is known yet about what they actually do. We are interested in Arl1 because we have found that the switch in Arl1, between the off position and the on position, is important for membrane traffic,” she explains, “and Mon2 is crucial for making the switch happen.

“As a result of this research, we made a fortuitous observation,” Dr. Rosenwald continues. “When we compare yeast cells with Arl1 to yeast cells without Arl1, we find that the ones without also have a potassium defect; that is, they are unable to take up potassium from the environment very effectively.”

Potassium is a vital contributor to cellular function. As the most abundant positively charged ion in cells, it serves several purposes, including facilitating the cell’s ability to make its own DNA and thus replicate. Dr. Rosenwald initially assumed that Arl1, because it regulates movement of proteins to the cell surface, was simply necessary for moving the protein required for potassium uptake to the cell surface. Hence, cells that lacked Arl1 would demonstrate problems with potassium uptake.

“However, once we dug a little deeper we saw that this was not the case, so now we’re in the process of figuring out why the Arl1-deficient cells don’t take in as much potassium,” she says. “So far, we have a set of intriguing observations, but no real answer yet. It’s somewhat like those six blind men on the cusp of discovering the elephant.”

Dr. Rosenwald’s interest in membrane traffic was first ignited while she was working toward her Ph.D. at the Johns Hopkins University.

“At that time,” she says, “new work was coming out of laboratories in California and Massachusetts showing that membrane traffic could be dissected using yeast as a model system. This breakthrough offered us a new avenue of study.”

In addition to her research in membrane traffic, Dr. Rosenwald has also worked fervently to bring a new undergraduate major to Georgetown in the Biology of Global Health, which will begin in the Spring 2008 semester.

“Broadly speaking, we want to try to understand and convey the human impact on the environment and vice versa. This major looks at the overall health of the globe from all angles, not simply human disease,” she explains. “It’s a great complement to other classes and programs that Georgetown already offers and it’s been generating significant interest from prospective students.”

The new major in the Biology of Global Health is emblematic of Dr. Rosenwald’s appreciation for Georgetown and its thriving biology program. The school has provided Dr. Rosenwald with the flexibility to dive into multiple areas of research and to apply different skills to her research and pedagogy of biology.

“Students are motivated, smart, and appreciative of the benefits they’ve received. They want to pay back. The Jesuit ideal is really present at this school. I’m always finding new ways to teach and work with our great students or to write about interesting scientific issues,” says Dr. Rosenwald. “In fact, I’m absolutely never bored.”

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