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COLLEGE STATION --

A select group of undergraduate biology majors at Texas A&M University are spending their spring semester getting up-close and personal with bread mold while test-driving their potential for research careers as participants in a large-scale, nationwide experiment involving analysis of the Neurospora crassa genome.

Eleven students currently are enrolled in a new upper-level course, "BIOL 489: Special Topics in Fungal Functional Genomics," taught for the first time this semester by Professor of Biology Dr. Matthew Sachs and funded as part of a $12 million National Institutes of Health (NIH) grant awarded through the National Institute of General Medical Sciences (NIGMS). The brainchild of Sachs, an international expert in fungal biology and the regulation of translation, and fellow biology professors Dr. Deborah Bell-Pedersen, an international expert in Neurospora crassa circadian rhythms and a prominent member of Texas A&M's world-renowned Center for Biological Clocks Research (CBCR), and Dr. Rodolfo Aramayo, an international expert in pathways that control gene expression during meiosis who also uses this fungus as a model, the course is educating students in phenotyping Neurospora knockout mutants as part of a widespread effort involving several universities and laboratories to better understand Neurospora crassa and its properties. Dr. Kari Halbig, a postdoctoral research associate with Sachs, is helping to supervise the laboratory studies.

Beyond mere course credit, the class offers a unique approach to getting students involved in a comprehensive experiment that they hope will benefit both the students and the scientific community. In addition to contributing to a national research effort in which student findings will be showcased side-by-side with those of principal investigators in the Neurospora crassa database housed at the Broad Institute in Cambridge, Mass., the class is providing students with a new means of getting valuable hands-on research experience in an environment in which many biology majors previously have not had the opportunity for research experience due to the limited number of faculty and laboratories available.

"It is top-notch research; they are finding out new things, and we can get more students research experience," Bell-Pedersen explains. "Many of them are considering graduate school, so this gives them a real push in that direction."

Senior genetics major Michael Guffey is one such student benefitting from the lab work who hopes to apply the experience to life after college.

"With a future career in plant science, this course has helped me better understand Neurospora crassa, a model for filamentous fungal pathogens that will still be relevant for years to come," Guffey says. "The work I have done previously in other labs has involved organic synthesis, biochemistry and some molecular genetics, but I have never seen the expression of mutations like this before [in Sachs' lab]. It's exciting to see genetics in this way, as phenotypes."

Understanding Neurospora crassa's physiological capacity has been the top priority of the investigators on this project since 2003, when the Broad Institute published the sequence of the genome on a National Science Foundation-funded project in which Sachs was one of the principal investigators. Once the information was made available, scientists in the fungal community were interested in taking it further, resulting in a multi-institutional Program Project grant (a "P01" in NIH parlance) led by National Academy of Sciences member Dr. Jay Dunlap of Dartmouth University. The subsequent, aggressive push to uncover as much as possible about the genome includes numerous universities, such as Texas A&M, the Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Oregon State University, University of Oregon, Oregon Health and Science University, University of California-Riverside, Ohio State University, University of Missouri-Kansas City, Boston University and Yale University. In the past five years, two-thirds of the genome's 10,000 total genes have been knocked out by researchers at Dartmouth and UC-Riverside.

When Sachs left Oregon Health and Science University to join the Texas A&M Department of Biology faculty in 2007, he brought the project with him. Bell-Pedersen subsequently joined the effort, adding the full resources of her own highly successful laboratory and the CBCR's recently renewed NIH grant to this multi-investigator nationwide educational and research effort.

"It's largely because of the great colleagues and resources for fungal biology that I was interested in moving to Texas A&M," Sachs notes. "I thought there would be great new opportunities to expand on the project."

In addition to the new course, the current grant also allots funds for Sachs and Bell-Pedersen to conduct individual research to develop new genomics tools to study environmental responses in Neurospora crassa, to knock out all the remaining genes in Neurospora to observe the genome's reaction, and to begin a similar project in the fungus Aspergillus.

Thanks to additional support for undergraduate research from Texas A&M, this project has been able to obtain several key pieces of equipment, including incubators to maintain the growth of the fungus under controlled environmental conditions, several state-of-the-art sterile hoods, and a camera-fitted microscope to record the growth of the mutant strains -- vital tools in carrying out the professors' research and in teaching the next generation of researchers enrolled in their class.

Sachs, Bell-Pedersen and other national investigators participating in the project currently are focusing on the complex phenomenon of how an organism responds to environmental signals -- or, in this case, what will happen after the organism responds to light or desiccation. This involves several techniques, including use of RNA sequencing -- Sachs' specialty -- to identify all of the RNAs in the organism that are altered following its exposure to light, as well as the use of ChIP sequencing -- the sequencing of DNA that is associated with specific factors in chromatin that have been purified by immunoprecipitation -- to identify all of the components in the gene expression network that respond to light exposure.

Educational experiences aside, one might wonder why it is so important to focus so much time, effort and money on studying the physical structure and environmental responses of a fungus? Sachs says light-signaling experiments on the fungus also will give researchers a genome-wide view of the signaling pathways from the environment to the cellular responses, which then can be compared to those in humans and other mammals. Furthermore, Neurospora crassa has proven to be a convenient model for basic research and is linked to plant and animal pathogens, as well industrial strains of fungi that yield antibiotics and pharmaceuticals.

"Studying these responses allows us to ask other questions," Bell-Pedersen adds. "Neurospora is an outstanding model system for what happens in humans. This student research has the potential to help us understand what happens in human disease and to identify new therapies."

For additional background and information on the Neurospora Genome Program Project, visit http://www.fgsc.net/Neurospora/neurospora.html.

To see data collected on Neurospora crassa thus far by Texas A&M students and other participants involved in the project, visit http://www.broadinstitute.org/annotation/genome/neurospora/MultiHome.html.

For more information on the grant, visit http://projectreporter.nih.gov/project_info_details.cfm?aid=7633564.

-aTm-

Contact: Chris Jarvis, (979) 845-7246 or cjarvis@science.tamu.edu; Dr. Deborah Bell-Pedersen, (979) 847-9237 or dpedersen@mail.bio.tamu.edu; or Dr. Matthew Sachs, (979) 845- 5930 or msachs@mail.bio.tamu.edu

Jarvis Chris

  • Dr. Matthew Sachs

  • Dr. Deborah Bell-Pedersen

  • Dr. Rodolfo Aramayo

  • Michael Guffey (right), a student in the course, examines with Dr. Matthew Sachs (left) some Neurospora cultures growing in race-tubes.

  • Kari Halbig (left), a postdoctoral researcher in Dr. Sachs' lab, and students Michael Guffey and Sofia Madinaveitia take a break from examining Neurospora cultures and their sexual development cycles. The computer monitor on the left shows the fruiting structures in the tissue culture flask illuminated on the microscope stage, while the monitor on the right displays photographs of Neurospora cultures growing in race-tubes.

  • Michael Guffey and Sofia Madinaveitia examine an image of the sexual fruiting structures of Neurospora. These structures, called perithecia, are dark because they contain melanin, the same pigment in human skin.

  • Asexual cultures of Neurospora. The powdery material at the top of each culture is asexual spores which are called conidia; each tube contains approximately one billion conidia. The orange color is from a Neurospora-produced pigment known as carotenoids.

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