Zemer Gitai likes to say of his thus far short, but fruitful, science career that he is devolving. Since he studied cancer in mice as an undergraduate student at Massachusetts Institute of Technology, he has been transitioning his work to increasingly simpler biologic systems. For now, he has settled on bacteria.
As a PhD student at the University of California, San Francisco, under the tutelage of Cori Bargmann, Gitai worked on axon guidance in Caenorhabditis elegans. In particular, he was interested in the parts of the worm's neurons that "know" when or where to grow, or fire, presumably working through a mechanism controlled by axon guidance and the eukaryotic actin cytoskeleton. But this work became frustrating, Gitai says, as he realized that in such a complex system with so many proteins, finding what controlled spatial cues would be daunting.
Gitai decided that a simpler system would help him get to the core of what controls the architecture inside cells. In 2003 he joined Lucy Shapiro's lab at Stanford University (to read about another of Shapiro's protégés, Sean Crosson, check out our December 2007 issue [21(12):67]). There, Gitai began his work on the bacteria Caulobacter crescentus, whose relatively small genome of approximately 4,000 genes and asymmetric shape and replication cycle seemed to provide a good model for studying the spatial development of cells.
Some clues about spatial development had appeared in 2001. A UK
research group identified a protein called MreB that seemed to play a
similar role in the eukaryotic cytoskeletal protein actin, which is
involved in morphogenesis. Gitai went on to show that in living cells
without MreB, the bacteria lose their elongated structure, form a helix,
and then die.
Instead of just deleting the gene, says Shapiro, Gitai wanted to block
the protein pharmacologically and observe the result. Scanning the
literature, he found that a Japanese researcher, Masaaki Wachi at the
University of Tokyo, while running assays on a library of chemicals affecting
Escherichia coli, had recently reported a compound
that caused the bacteria to round up. In what Shapiro calls "classic aggressive
Gitai style," Gitai immediately contacted Wachi to obtain a sample of the
compound, called A22. Gitai "demonstrated quite elegantly in  that the
tiny molecule [became] bound to an ATP-binding site in MreB and inhibited its
action," says Shapiro.
In the late spring of 2005, Gitai gave a talk at Princeton University about his findings in Caulobacter, and within weeks he was offered a tenure-track position. "His work is spectacular," says Lynn Enquist, chair of the Princeton molecular biology department. Gitai has shown that biologic processes normally associated with eukaryotes are also occurring in bacteria, adds Enquist. In yet unpublished work, Gitai's lab has expanded his study of proteins and observed that as many as 15% localize to a specific place in the bacteria, depending on their function. Moreover, the MreB protein forms a vital network for trafficking proteins and DNA throughout the cell. "Before we showed that a blueprint exists," says Gitai, "people thought bacteria were just bags of enzymes."
Title: Associate Professor, Department Molecular Biology,
1. Z. Gitai, "An actin-like gene can determine cell polarity in bacteria," Proc Nat Acad Sci, 101:8643–8, 2004. (Cited in 86 papers) 2. Z. Gitai, "The new bacterial cell biology: moving parts and subcellular architecture," Cell, 120:577–86, 2005. (Cited in 41 papers) 3. N.A. Dye et al., "Two independent spiral structures control cell shape in Caulobacter," Proc Nat Acad Sci, 102:18608–13, 2005. (Cited in 32 papers)