Tuesday, July 27, 2010

Susan Forsburg: Making the Most With Yeast

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Making the Most With Yeast
Susan Forsburg, center, holds petri dishes containing S. pombe inside her lab, with postdoctoral researcher Sarah Sabatinos, left, and Ph.D. student Pao-Chen Li.
Photo/Eric O'Connell

By Pamela J. Johnson on July 27, 2010 7:36 AM

There is good reason Susan Forsburg’s laboratory smells of sourdough.

The USC College biologist is among the most prominent fission yeast researchers in the country. Inside her lab are hundreds of petri dishes containing cultures of Schizosaccharomyces pombe — a single-celled fungus Forsburg and her team use to study DNA damage and mutation that in humans may lead to cancer.

“It’s a friendly, fast, nontoxic organism,” said Sarah Sabatinos, one of two postdoctoral researchers who work in the Forsburg laboratory, along with six graduate students, five undergraduates and three technicians. “And it smells good, too.”

Providing a deeper understanding of how cells work, Forsburg’s research ultimately will be used as the foundation to improve treatment and seek cures for cancer.

“I don’t expect anything I do to cure cancer,” Forsburg said bluntly. “The way basic science works is every scientist puts a brick in the wall. And the person who makes news is the scientist who puts the last brick in the wall. But he or she wouldn’t be anywhere without all the pieces underneath.”

S. pombe — Forsburg’s expertise — is dubbed a micro-mammal because it can be used as a genetic system to model processes that apply to higher cells. Pombe means beer in Swahili. The yeast originally was isolated in 1893 from East African millet beer.

The fungus can be used for brewing, but the beer can taste and smell of sulfur, akin to rotten eggs. It also can be used to bake, but the bread won’t rise as well as if made from baker’s yeast — or Saccharomyces cerevisiae — the most common yeast microbiologists use to research cell division.

“We’re the other yeast,” Sabatinos said. “S. pombe is a great model organism that can answer basic research questions. I think of pombe as a cross between humans and plants. Pombe has many of the genes humans have.”

When giving presentations for the American Cancer Society, Forsburg tells the audience to consider a pombe cell a lawnmower and a mammalian cell a Mercedes Benz.

“We can learn from a simple piece of machinery like a lawnmower before seeing how the Mercedes works,” Forsburg tells the audience.

If you Google S. pombe, Forsburg’s award-winning Web site PombeNet is among the top results. The site answers many questions about fission yeast research. During an interview, Forsburg elaborated, explaining that normal cell division is essential to healthy development in human and yeast cells. Since human cells are so complicated, it is easier to establish basic principles in simple model organisms.

Scientists know that malfunctions during cell division can lead to cancer or birth defects. Forsburg researches a crucial part of cell division: the start of the replication of DNA in the parent cell prior to the point when it distributes its DNA among its daughter cells. Each human DNA molecule is comprised of chemical bases arranged in 3 billion sequences. If laid end-to-end, the DNA in a single human cell measures 3 1/3 feet.

The DNA of one cell contains so much information that if represented in printed words, listing just the first letter of each base would require more than 1.5 million pages of text. Mistakes in copying or repairing DNA can result in cancer.

“A characteristic of cancer cells is genome instability,” Forsburg said. “Cells can start to make more mistakes; they may not replicate properly or divide properly. They break their chromosomes, they lose chromosomes, they have too many of one, not enough of another. This leads to disruptions in gene activities. So we’re using fission yeast as a model system to try to understand the cellular mechanisms that create genome instability.”

S. pombe cells grow quickly, between two and four hours, and they are easy to manipulate in the laboratory.

“I’m a really passionate advocate for the organism,” Forsburg said. “I basically proselytize the use of this system for studying problems relating to how chromosomes behave.”

She shows her advocacy with a touch of humor. On her office wall hangs a photograph of the famous Hollywood sign. But rather than Hollywood, she Photoshopped the iconic white letters to say “Pombewood” and made Pombewood T-shirts for her students.

On another wall is a photo of Sir Paul Nurse, Leland Hartwell and Timothy Hunt, awarded the 2001 Nobel Prize in Physiology or Medicine for their cell division cycle research. Nurse investigated the life cycle of S. pombe, discovering a key gene species that helps control cell division. He was the scientist who transformed S. pombe into a forefront model system.

As a postdoc at Oxford University, Forsburg worked in Nurse’s lab. She earned her bachelor’s in molecular biology and English literature at the University of California, Berkeley (her hometown), and Ph.D. at the Massachusetts Institute of Technology.

When Forsburg returned to the United States in 1993 to become an assistant professor at the Salk Institute for Biological Studies in La Jolla, she began receiving queries about pombe. She created pombe.net and has become the nation’s unofficial pombe spokesperson.

At USC College since 2004, Forsburg has earned numerous honors, including being named a fellow of the American Association for the Advancement of Science, the Association for Women in Science and the USC Center for Excellence in Research. She also received a USC-Mellon Award for Excellence in Mentoring.

She is on the American Cancer Society’s Council for Extramural Grants and speaks to potential donors about her research.

“You may think that a talk about yeast research would be like watching ice melt,” said Gail Berlant, director for distinguished giving at the organization’s Los Angeles office. “But Susan makes people excited about what she does. Scientists like Susan are society’s true rock stars.”

Astrid Schnetzer: Microbes on the Menu

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Microbes on the Menu
Phytoplankton in mixed communities

The functioning of marine ecosystems depends on the size and flavor of microbes at the base of the food chain. Changes to the Earth's atmosphere might rearrange that microscopic menu.

Microbes that currently are the main course for other organisms might get harder to find in the future, and microbes that are now inconspicuous as members of a "rare biosphere" might become more common.

Four biologists at USC College have started work on a project funded by the National Science Foundation to examine the changes that might occur within communities of marine microbes as seawater becomes more acidic, a change that is happening as the rising levels of carbon dioxide in the atmosphere are absorbed by the ocean.

The principal investigator on the project is Astrid Schnetzer, a research assistant professor in the USC marine environmental biology program who said the study will examine the response of microbial communities to ocean acidification and increases in temperature.

"The change that is happening is very complex — it won't be just an increase in carbon dioxide in the water or an increase in temperature," Schnetzer said. "Global climate change will affect a whole suite of ocean properties, directly or indirectly, in the coming decades."

Schnetzer is working on the project with three other faculty members in marine environmental biology: professors David Caron and David Hutchins, and research assistant professor Feixue Fu. All are affiliated with the USC Wrigley Institute for Environmental Studies.

During the three-year study, Schnetzer and her colleagues will look within natural communities of microbes for specific species that can beat their competitors because they acclimate better to the altered temperature and chemistry of seawater in a "greenhouse world." The researchers will isolate microbes that pass the "acclimation test," cultivate them for several generations and then recombine them to examine the structure of their communities under conditions that are predicted for the future.

"The species that can acclimate better to changes in CO2 levels will have a competitive advantage," Schnetzer said.

The new study at USC will do more than evaluate the individual species that might survive the marine conditions that are predicted for the future. It will monitor the growth rates and elemental composition of phytoplankton under new conditions and the "functional groups" of organisms that might emerge in the future.

The "primary producers" are one of the most critical of these functional groups. These are the algae capable of photosynthesis that create plant material out of sunlight, carbon dioxide and ambient nutrients. Schnetzer said these algae might change as the chemistry and temperature of seawater change. The algae might grow more quickly or slowly, or bigger or smaller. They might become more or less palatable and more or less nutritious.

The other microbes and crustaceans that feed on these algae, in turn, will react to any changes in the plant material that is fundamental to their diets.

"The reason the primary producers are so important is because, ultimately, they're the base of food chain," Schnetzer said. "Whatever affects them will affect anything else that's higher up. That means the protozoa that graze on them, the zooplankton that graze on them, small crustaceans, fish — and somewhere up that food chain we find ourselves."

In addition to providing food for other marine organisms, the primary producers influence the chemistry of seawater because they remove carbon dioxide from it.

Seawater absorbs carbon dioxide from the atmosphere, and the primary producers convert dissolved CO2 into plant matter. Schnetzer said the microbes are on the front lines of "carbon sequestration" on a global scale, but changes to the temperature and chemistry of seawater in a "greenhouse world" might change the growth rates of the primary producers. That would change the rate at which they remove carbon dioxide from the water and their capacity to assist in the sequestration of CO2 from the atmosphere.

Schnetzer said changes in water chemistry also might open a window of opportunity for species of microbes that typically exist at very low numbers. Organisms that are now part of this "rare biosphere" might thrive under new conditions, and in some cases they might become very conspicuous members of a new order.

"Harmful algal blooms could be considered a 'real world' example of the rare biosphere," Schnetzer said. "You know that these species of algae are around, but they're not really abundant; they're somewhere in the very background of what's present at any given time. Then, something in the environment changes, a window of opportunity opens and they suddenly take over and dominate."

The ocean naturally absorbs carbon dioxide from the air. Over the course of millions of years, the balance of CO2 in the air and in seawater reached equilibrium, and so did the chemistry of the seawater. But the burning of fossil fuels for energy adds billions of tons of carbon dioxide to the atmosphere every year, and as the atmosphere becomes more saturated with carbon dioxide, so does the seawater. The marine life we know today is suited for the equilibrium as it exists now, but rising levels of carbon dioxide in the environment are pushing ocean chemistry out of this age-old balance.