Research on the DNA in the sperm of tiny soil worms sheds new light on the causes of human male infertility. Diana S. Chu, assistant professor of biology, is lead author on the paper, "Sperm Chromatin Proteomics Identifies Evolutionarily Conserved Fertility Factors," which identifies new proteins critical to the production of healthy sperm. Chu's cutting-edge research is the cover story of the Sept. 7 issue of the journal Nature.

Male infertility contributes to about 30 percent of reproductive failure in the United States. "Male fertility treatments go around the cause," Chu said. "No one knows the molecular basis of infertility ... how the proteins work." Her research concentrates on identifying these causes. The identification of the factors that function in fertility and reproduction could define new avenues for understanding human male infertility, finding appropriate treatments, and/or identifying male contraceptive methods.

Chu uses the one-millimeter long worm, Caenorhabditis elegans, as a model for understanding how the DNA content of sperm is assembled. "This species is very useful to us because its genome is completely sequenced," Chu said. "It does many of the same processes that we do but the complex process of making sperm is much simpler in worms than humans."

The cover photo for the Nature article was taken by Chu under a high-powered microscope. She used dyes that react to fluorescent light to identify the DNA (red) and proteins (green) and find where these overlap (yellow) in the worm's sperm.

The idea for Chu's research came from the observation that the way worm sperm DNA is packaged looked similar to that of humans. "We decided to look for proteins that associate with sperm DNA and found that they are important for fertility in C. elegans," Chu said. Her team also found that the majority of proteins in the worms have similar counterparts in mice and humans, and that some of the mice proteins were also required for fertility.

Chu, whose passion for biological research began in a high school program that allowed her to assist in college lab research, initiated this project as a postdoctoral fellow in the laboratory of Barbara J. Meyer at University of California, Berkeley. Research colleagues also included Tammy F. Wu, a postdoctoral researcher at SF State; Hongbin Liu and John Yates III of The Scripps Research Institute; and Edward J. Ralston and Paola Nix of University of California, Berkeley. Chu said that Ahna Skop, a former colleague in Meyer's lab who is now at University of Wisconsin, urged her to pursue the research with methods that proved to be unusually efficient.

"As with all research, we began with an idea and a few hunches," Chu said. "But unlike most explorations, almost every one of these ideas turned out to work. It was an exciting trip."

Chu's research at SF State will continue with the same focus. Like all SF State faculty conducting high level research on campus, Chu makes a point of staffing her lab with undergraduate and graduate students. Funding for her work comes from the National Institutes of Health and the National Institute of General Medical Science's Minority Biomedical Research Support-Support of Continuous Research Excellence (MBRS-SCORE) program, which provides infrastructure that allows college students to participate in important research.

-- Denize Springer
Image: Courtesy of Nature