Bread Mold, a Blot on a Bun, is a Star in the Lab

Texas A&M Biologists Describe Genome in Landmark ‘Nature’ Edition

COLLEGE STATION -- In the fungus world, new stars keep popping up. The clammy kingdom of mushrooms, molds, blights and blasts has sprouted delicacies as coveted as truffles and staples as common as baker's yeast, not to mention scourges like histoplasmosis and athlete's foot.

In such a high-profile lineup, the fuzzy orange mold that spoils leftover loaves and muffins often goes under-appreciated.

But the bread mold known to science as Neurospora crassa has made careers, spun off Nobel prizes and laid the foundation for much of modern biology, said Rodolfo Aramayo, a Texas A&M University biologist whose specialty is evidenced by the plastic toadstool sprouting on his office file cabinet.

Assistant Professor Aramayo and Associate Professor of Biology Deborah Bell-Pedersen contributed to a landmark paper, published in the April 24 issue of Nature, announcing the sequencing of the N. crassa genome. It was a major event. After all, while bread mold may be a mere annoyance in the pantry, as a research model it ranks with the fruit fly.

Associate Professor Deborah Bell-Pedersen in her lab - part of the newly established Center for Biological Clocks Research at Texas A&M University.

The Nature paper announcing the sequencing, published in the special edition celebrating the 50th anniversary of the discovery of the DNA double helix, drew together contributions from leading N. crassa researchers around the world. The presence of two Texas A&M biologists (along with Robert Pratt, a biology graduate student working under Aramayo, and Professor Daniel Ebbole of the Department of Plant Pathology and Microbiology) reflects an area of scientific strength on campus, Aramayo said.

"One of the strongholds of A&M is the filamentous fungal community," he said.

Now that the N. crassa genome is all but complete, Bell-Pedersen, Aramayo and fellow researchers in the world's fungus labs hold a key that promises to accelerate progress on scientific frontiers with important human health implications. Bell-Pedersen, for instance, uses N. crassa to plumb the workings of biological clocks, those internal timers that set daily rhythms in people, plants and other organisms. The clocks are believed to be central to understanding some sleep and mood disorders.

Aramayo, meanwhile, studies the fungus for insights into epigenetics, a new branch of science that picks up where DNA leaves off in explaining how genes can be regulated by small bits of RNA. His lab focuses especially on revealing the machinery of meiotic RNA silencing, which concerns novel mechanisms ultimately believed to control chromosome pairing and to maintain the integrity of the genome. The research raises startling questions and promises new insights into speciation and perhaps some facets of human reproduction.

N. crassa mutant - "scumbo" - taken with an electron micrograph by Matt Springer, Stanford University at the Fungal Genetics Stock Center.

The sequencing of N. crassa was conducted at the Whitehead Institute Center for Genome Research, in Cambridge, Mass., during a two-week hiatus in the human genome project, Bell-Pedersen said. Though the fungus joins an expanding list of species to be sequenced, its presence is conspicuous -- it is the first published fungus genome more complex than single-cell yeast.

To describe the results, Nature invited analysis from 77 scientists from labs as far away as Scotland and Israel. Analyzing the data and drafting a paper with so many authors took much longer than the sequencing itself, Bell-Pedersen said. The writing involved several working groups and "one conference call after another," she said. The group assembled last October in Boston to put final details in place.

The Texas A&M contributions are substantial -- and no wonder.

N. crassa has helped make the Department of Biology a world leader in biological clocks research, with a $5 million research grant from the National Institutes of Health backing a newly approved Center for Biological Clocks Research. Even before the N. crassa genome was announced, Bell-Pedersen's lab, in collaboration with Ebbole's lab, had manufactured the first "DNA chips" containing genes from the fungus. DNA chips, also called "microarrays," bring a touch of Silicon Valley to biology labs, by arraying thousands of genes on a slide much as circuits are etched into a silicon wafer. Scientists can then scan the chips to see how genes are expressed. For instance, they can see how genes change their expression according to a daily schedule governed by a biological clock. N. crassa's daily routine includes changing growth patterns in the early morning.

N. crassa samples growing in Dr. Deb Bell-Pedersen's lab.

Bell-Pedersen's N. crassa arrays, which contained about 15 percent of the genome, were the first DNA arrays from the fungus. They already are yielding strong results.

A pending paper based on the arrays will reveal that the clock regulates about 20 percent of the genes, Bell-Pedersen said. "That was a big surprise," she said. "That's a huge number." The revelation has led her to hypothesize that the mold has multiple oscillators controlled by a master clock -- just as in people. That arrangement would make the mold even more valuable as a model.

N. crassa also is a key organism in the kind of gene silencing that Aramayo conducts in his lab. RNA silencing is particularly well documented in the mold, he said.

An "old-school" lab organism that was a favorite of "the very people who invented genetics," N. crassa has yielded many secrets over the years, Aramayo said. In 1958, George Beadle and Edward L. Tatum won the Nobel Prize for work with the fungus that led to their "one-gene, one-enzyme" hypothesis. The fungus has attracted other scientists as eminent as Barbara McClintock, who won a Nobel Prize for her work with corn but who also developed the foundation for fungal meiotic cytology by describing and observing the behavior of Neurospora chromosomes, Aramayo said.

Aramayo uses the fungus as a model to understand epigenetic questions such as how the pairing of DNA in developing zygotes controls gene expression. His lab, which has pioneered some of the technology speeding the research, is one of the few in the world that uses N. crassa as a model for such studies.

The potential implications for human health are vast, with obvious possibilities in addressing human reproductive problems. "When it comes to sex," Aramayo said, "molds and humans share at least one fundamental principle. In both species, the parents must donate a copy of their DNA to the offspring in order to successfully reproduce.

"There are molecular mechanisms in Neurospora crassa that are similar to molecular mechanisms in human cells," he said. "They help us understand how things go wrong."

The genome already has revealed a few surprises, Aramayo and Bell-Pedersen said. For one, the fungus was found to have genetic mechanisms for fighting off invading viruses.

It also has genes that allow it to sense red light.

But no one is stopping. To the contrary, for N. crassa researchers like Aramayo and Bell-Pedersen, the sequencing of the genome means "Go."

Contact: Mark Minton, Communications Specialist, Texas A&M College of Science (979) 862-1237 or mminton@science.tamu.edu; Deborah Bell-Pedersen (979) 847-9237 or dpedersen@mail.bio.tamu.edu; Rodolfo Aramayo (979) 862-4354 or raramayo@bio.tamu.edu

Minton Mark

2003-05-12 00:00:00