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

Our research interests and experimental approaches range widely. We work to answer questions about bacterial development and life history, including the mechanisms that underlie observed phenotypes, and the evolutionary forces that shape them:

• How do bacteria regulate the complex task of differentiation to create distinct cell types and morphologies?
• How do individual bacteria coordinate their adhesion to surfaces? What role does adhesion play in community ecology?
• Why do bacteria age, and what mechanisms drive the aging process?

As a model, we study the simple differentiating bacterium Caulobacter crescentus in which each cell division produces a motile swarmer cell and a stalked cell. In addition to differences in morphology, the two progeny cells have different fates. Only the stalked cell is competent to replicate DNA and divide. Caulobacter is easy to grow, has excellent genetics and a sequenced genome, and is ideally suited for cell biological approaches.

Regulation of cell differentiation. The different stages of polar development in Caulobacter are tightly coordinated with the cell cycle. We study transcriptional and proteolytic regulatory mechanisms and regulators that control the timed and ordered progression of these stages. We also study a checkpoint that couples polar development with cell division.

Control of cellular asymmetry. Before they divide, Caulobacter cells are asymmetric with a flagellum at one pole and a stalk and adhesive holdfast at the other pole. We have used genetic and molecular methods to identify genes that are involved in the maintenance of cellular asymmetry and we are studying their mechanism of action. We also have a strong interest in the mechanisms that target proteins and structures to a specific pole of the cell

Bacterial adhesion and biofilm formation. Adhesion is an important component of bacterial infections and is the first step of biofilm formation. In Caulobacter, adhesion is mediated by the holdfast, a complex polysaccharide with strong adhesive properties found at the tip of the stalk. We study the mechanism and regulation of single cell attachment to surfaces, holdfast synthesis, and the subsequent events that lead to the formation of biofilms.

Evolutionary genomics. We are taking advantage of next generation sequencing methods to sequence the genome of bacteria closely related to Caulobacter to investigate the evolution of cell shape and differentiation and the regulatory networks that control them.

Bacterial aging. Recent work has shown that organisms previously thought to be immortal, such as bacteria, demonstrate age-specific declines in reproduction. Asymmetry is thought to be important for aging by allowing the preferential segregation of damaged molecules to mother cells. We are using the asymmetrically dividing Caulobacter and close relatives that divide by the even more asymmetric mechanism of budding such as Hyphomonas to address the mechanism of aging and the role of asymmetry in this process.

Experimental approaches. We use a multitude of approaches that include mathematical modeling, biophysics, biochemistry, molecular biology, cell biology, microscopy, genetics, genomics, and proteomics. Our wide range of expertise and excellent collaborators allow us to focus on biological questions rather than specific methods and provides an outstanding multidisciplinary environment.

Brown, P., G. Hardy, M. Trimble, and Y. V. Brun. Complex regulatory pathways mediate cell cycle progression in Caulobacter crescentus.  2009.  Advances in Microbial Physiology Volume 54, p. 1-101, Elsevier Press, R.K. Poole, editor.

Toh, E, H. D. Kurtz, Jr., and Y.V. Brun. 2008. Characterization of the Caulobacter crescentus Holdfast Polysaccharide Biosynthesis Pathway Reveals Significant Redundancy in the Initiating Glycosyltransferase and Polymerase steps. Journal of Bacteriology, 190, 7219-7231. [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.

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, 26, 4694-4708. [abstract]

Lawler, M.L., and Y.V. Brun. 2007. Advantages and mechanisms of polarity and cell shape determination in Caulobacter crescentus. Current Opinions in Microbiology, 10: 630-637. [abstract]

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.

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]

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]

Badger, J.H., T.R. Hoover, Y.V. Brun, (24 other authors), and N. L. Ward. 2006. The genome sequence of the marine prosthecate a-proteobacterium Hyphomonas neptunium ATCC 15444 and its comparison with Caulobacter crescentus CB15. Journal of Bacteriology, 188: 6841-6850. [abstract]

Li, G., C. S. Smith, Y. V. Brun, and J. X. Tang. 2005. The elastic properties of the Caulobacter crescentus adhesive holdfast are dependent on oligomers of N-acetylglucosamine.  Journal of Bacteriology, 187: 257-265.