Unraveling The Bertozzi group confronts one of the world’s major killers
KATHEEN DURKIN
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To p Carolyn Bertozzi takes a break from her responsibilities as the director of the LBNL Molecular Foundry.
B o t t o m Joseph Mougous, a former member of the Bertozzi research group, is now an assistant professor at the University of Washington. College of Chemistry, UC Berkeley
JOSEPH MOUGOUS
M i d d l e A molecule of SL-1, a virulence factor in the cell wall of TB bacteria.
n the fall of 1999, Joseph Mougous, a new graduate student in the research group of professor Carolyn Bertozzi, started looking for a research project. Mougous began by exploring the genetic sequence of the tuberculosis (TB) bacterium that had been published the previous year. In the sequence he found something unexpected, something that would eventually lead not only to his own dissertation, but also to a new research focus for the Bertozzi group — one that continues to gain momentum eight years later. Buried in the genetic code of the TB bacterium, Mougous found genes for the production of a set of enzymes that were very similar to those in humans. The enzymes helped produce sulfated glycolipids, molecules involved in cell-to-cell communication in higher animals. What were these genes doing in a bacterium, he wondered? Were they an integral part of the microbe’s genome, or were they evolutionary baggage, bits of junk DNA? Did they help produce the unique characteristics of TB that make it so dangerous and difficult to treat? The researchers who first published the TB genome in Nature magazine (11 June 1998) had noted many unusual aspects of the bacterium. “Novel biosynthetic pathways generate cell-wall components and several of these may contribute to mycobacterial longevity,” the researchers wrote. “…TB contains an additional layer that is exceptionally rich in unusual lipids, glycolipids and polysaccharides.” Starting from these genetic clues, Mougous and the Bertozzi group began their search to understand the TB bacterium and to find new ways to disrupt its lifecycle. The terms “glyco” and “saccharide” are hints that these complex organic molecules are built from simpler sugars. For Bertozzi, understanding the chemistry of these sugarbased molecules, and the role they play in disease and health, including cancer and inflammatory disease, has become her life’s work. Bertozzi is the T. Z. and Irmgard Chu Distinguished Professor of Chemistry and professor of molecular and cell biology at Berkeley. She obtained her undergraduate degree from Harvard University in 1988 and her Ph.D. from Berkeley in 1993, both in chemistry. After a postdoctoral appointment at UCSF, she returned to Berkeley as a faculty member in 1996. She is also an Investigator of the Howard Hughes Medical Institute, a faculty affiliate at QB3, and