Georgetown College. Georgetown University.

By LiAnna Davis

Georgetown’s Dr. Ronda Rolfes enjoys teaching all of her courses, but Genetics holds a special place in her heart. She tries to convey this feeling to the 100 sophomores who take the class each fall.

“It’s the course that hooked me on science,” she confesses. “I was at the edge of my seat, wanting to know why we don’t know things. Now, I love to teach it and convey my passion and love of the subject to students.”

Dr. Rolfes knew she wanted to be a scientist and teacher from her undergraduate Genetics course and pursued her goals through her Ph.D. in biochemistry looking at cellular responses in gene control with the Escherichia coli bacterium. For her postdoctorate work, Dr. Rolfes started focusing on the yeast system Saccharomyces cerevisiae, and she continues that work today as a professor in the Biology Department.

All organisms have a genetic system, but yeast genetics are very simple and easy. Yeast can grow with two copies of their genome (diploid, like humans) or with only one copy (haploid content, like egg and sperm cells); this ability permits researchers to isolate or create mutants and to see the effects of the mutation. Scientists like Dr. Rolfes also find it easy to manipulate the yeast genome by knocking out, adding in, or replacing genes.

“Analysis of yeast mutants allows researchers to study cellular processes, particularly the machinery associated with transcription and translation, DNA replication and repair, metabolic and signaling pathways, and protein trafficking,” explains Dr. Rolfes. “These basic processes are fundamentally the same in higher—but slower—eukaryotes, although they are more complex there than in yeast. Thus we can gain insights into these processes in the simpler system.”

Saccharomyces cerevisiae, one of the best understood organisms, is a multipurpose yeast that bakers, brewers, and scientists all find critical to their work. Scientists like Dr. Rolfes use Saccharomyces cerevisiae as a model organism for cells. Model organisms provide a frame of reference for scientists—for example, Dr. Rolfes’ colleague Elena Casey studies the Xenopus laevis frog, another model organism, to learn about vertebrae development. Other animals, plants, and insects also serve as model organisms, each to understand a different piece of biology and nature.

“Saccharomyces is great for understanding basic issues of how a cell functions and how a eukaryotic genome works,” Dr. Rolfes says. “Yeast was the first eukaryote to have the sequence of its genome determined. Scientists use it as a bench mark for other genomes (such as ours), to understand how genes are organized in the genome, to decipher the additional roles for DNA besides protein coding regions, and to see how DNA changes over evolutionary time.”

Her research focuses on cell function, looking at how cells sense what is happening in their environment and how they communicate with the outside environment. She uses an analogy to describe the basic question: If you are reading by your window and it is daylight, you will not need to turn on a light. If you enter the room and it is dark, however, you will need to turn on the light in order to read. How can you grasp the need to turn on the light? How do you signal that information? What is necessary to produce light? The sensing and signaling processes of cells at the molecular level are what fascinates Dr. Rolfes.

“Cells are economical with their distribution of resources,” she says. “When a cell has lots of nucleotides (the structural basis of RNA and DNA), it can divide and grow. I examine how cells decide if the nucleotides are there and if there are enough to divide.”

In addition to studying the Saccharomyces yeast, Dr. Rolfes examines the Candida albicans yeast, which is responsible for medical problems like vaginitis in women and thrush in infants. Both organisms shared a common ancestor about 200 million years ago, but today, they are very different from each other in their genetic systems, responses to environmental stimuli, and pathogenesis, in spite of looking almost identical as yeasts. Although common, Candida albicans causes deep concern in the medical community.

“If the immune system is compromised—perhaps for a genetic reason or by disease—yeast infections can be lethal,” explains Dr. Rolfes. “They can invade the body, colonize internal organs, and disrupt organ function.”

Yeast tends to grow in round shaped cells, but Candida albicans can undergo a change in shape in which the cells make long projections called hyphae. This change in shape in Candida albicans has been causally linked to disease. Dr. Rolfes’ lab—which includes post-doctorates, Ph.D. students, master’s students, and advanced undergraduates—has isolated a protein that is important in the switch. With a recent grant from the National Institutes of Health, they are now examining the filamentation process using genetics in hopes of reducing the harmful effects of Candida albicans.

Dr. Rolfes admits that testing each variable independently can be tedious, but she still enjoys the research process.

“My favorite part of research is discovering something new that no one has ever seen before. You’re the first one to do it. It feels like you’re banging your head against the wall, but then you get it,” she says. “It’s a very creative process; something beautiful now exists because you’ve figured it out, you’ve uncovered something that exists in nature. It’s astounding that you can do that.”

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