Clyde Culbertson Professor of Biology
Ph.D., Université Laval, Québec, Canada, 1990
Postdoctoral Fellow, Stanford University, 1990-93

Program Affiliation: Molecular Biology & Genetics | Microbiology

Research Groups Affiliation: Biochemistry | Cell Biology | Development | Genetics | Genomics & Bioinformatics | Microbiology

1997, Senior Class Award for Teaching Excellence in Biology
1998-2003, National Science Foundation CAREER Award
1999, Department of Biology Teaching Excellence Recognition Award
2001, Indiana University Trustees Teaching Award.
2003-2007, Editor, Journal of Bacteriology
2005, IBASM Academic Scientific Achievement Award
2006, Top 2006 Stories in Science by The Future of Things

The main goal of our research is to understand how cell division and cell differentiation are regulated and integrated to generate two different cell types. We study the simple differentiating bacterium Caulobacter crescentusin which each cell division produces a motile swarmer cell and a stalked cell that attaches to surfaces via its adhesive holdfast. In addition to differences in morphology, the two progeny cells have different fates. Only the stalked cell is competent to replicate DNA and divide. Caulobacteris particularly well suited for studies of cell division and differentiation since cell populations can be synchronized and the different stages of the developmental pathway have distinct morphologies. In addition, the entire genome of Caulobacterhas recently been sequenced, greatly facilitating experimental manipulations. For example, we are using genomics, 2D gel electrophoresis, and proteomics to identify genes regulated by different signal transduction pathways.

Regulation of the cell cycle. We study the regulation of cell division and DNA replication genes to gain an understanding of how the cell regulates its cell cycle. We have identified transcriptional and proteolytic regulatory mechanisms that control the timed and ordered expression of cell division proteins. We have found checkpoints that couple the expression of cell division genes to DNA replication and we are trying to identify the regulators responsible for this coupling.

Assembly and function of the cell division complex. We study the structure-function of cell division proteins to determine how they interact. We use many cell biological and microscopic techniques to study how cell division proteins are targeted to the site of cell division and how they are assembled in the multiprotein cell division complex. In particular, we have recently used site-directed mutagenesis coupled to molecular modeling and biochemistry to study the structure-function of FtsZ, a bacterial GTPase required for cell division.

Control of cellular asymmetry. Before they divide, Caulobactercells are asymmetric with a flagellum at one pole and a stalk and holdfast at the other pole. We use genetic and molecular methods to identify genes that are involved in the maintenance of cellular asymmetry. We have identified mutants that have lost their cellular asymmetry and that synthesize a stalk and a holdfast at both poles of cells. Genes identified by this method include a sigma factor and a response regulator involved in a signal transduction pathway that couples polar development to cell division.

Bacterial adhesion. Adhesion is an important component of bacterial infections. In Caulobacter,adhesion is mediated by the holdfast, a complex polysaccharide with strong adhesive properties found at the tip of the stalk. The stalk and holdfast are synthesized at the same pole of the cell during the same stage of the developmental program. Using genetic screens, we have identified genes required for holdfast export and attachment and we are studying their function. We are particularly interested in how the holdfast is localized to a specific pole of the cell.

Proteomics. The recent completion of the genomic sequence of the Caulobacter genome provides new avenues to study the control of cell differentiation. We have initiated a collaboration with Dr. Jim Reilly, an expert in MALDI-TOF mass spectrometry, to use proteomics to study the various problems described above. In addition, we are developing novel methods for proteome analysis.

Li, Z., M. Trimble, Y.V. Brun, and G. Jensen. 2007. Direct in situ Visualization of FtsZ Filaments in Caulobacter crescentus by Electron Cryotomography. The EMBO Journal, advance online publication 18 October 2007; doi: 10.1038/sj.emboj.7601895. [abstract]

Wagner, J.K. and Y.V. Brun. 2007. Out on a limb: how the Caulobacter stalk can boost the study of bacterial cell shape. Molecular Microbiology, 64: 28-33.

Wagner, J.K., S. Setayeshgar, L. Sharon, J. Reilly, and Y.V. Brun. 2006. A nutrient uptake role for bacterial cell envelope extensions. PNAS, 103: 11772-11777. [abstract | full text pdf | commentary]

Lawler, M.L. and Y.V. Brun. 2006. A molecular beacon defines bacterial asymmetry. Cell, 124, 891-893.

Tsang, P., G. Li, Y.V. Brun, B. Freund, and J. X. Tang. 2006. Adhesion of single bacterial cells in the micronewton range. PNAS, 103: 5764-68. [abstract | commentary in Nature]

Pierce, D.L., D.S. O’Donnol, R.C. Allen, J.W. Javens, E.M. Quardokus, and Y.V. Brun. 2006. Mutations in divL and cckA suppress a divJ null mutant in Caulobacter crescentus by reducing CtrA activity. Journal of Bacteriology, 188:2473-82.

Lawler, M.L., D.E. Larson, A.J. Hinz, D. Klein, and Y.V. Brun. 2006. Dissection of Functional Domains of the Polar Localization Factor PodJ in Caulobacter crescentus. Molecular Microbiology, 59: 301-316.

Wagner, J. , C. Galvani, and Y. V. Brun. 2005. Caulobacter crescentus requires RodA and MreB for stalk synthesis and to prevent ectopic pole formation. Journal of Bacteriology, 187: 544-53.

Bodenmiller, D., E. Toh, and Y. V. Brun. 2004.  Development of surface adhesion in Caulobacter crescentus.  Journal of Bacteriology, 186: 1438-47.

Martin, M., M. Trimble and Y. V. Brun.  2004.  Cell cycle-dependent abundance, stability and localization of FtsA and FtsQ in Caulobacter crescentus.  Molecular Microbiology, 54: 60-74.