29-05-2012, 01:06 PM
Cellular differentiation and cell division in bacteria
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In recent years, advances in microbial cell biology have led to a fundamental change in the perception of bacteria. While previously envisioned as membrane-bounded conglomerates of enzymes, bacterial cells have now emerged to be highly organized entities that tightly regulate cell shape and polarity, actively segregate plasmids and chromosomal DNA, and frequently undergo complex differentiation processes. As in eukaryotes, their temporal and spatial organization is controlled by multi-component regulatory networks, involving localized protein complexes and dynamic cytoskeletal structures. However, despite the progress made, the current knowledge on cellular organization in bacteria is still very limited, providing ample opportunities for future research.
The aim of our group is to understand the molecular basis of cellular differentiation, morphogenesis, and cell division in bacteria and to elucidate how one-dimensional genetic information is translated into defined spatial and temporal regulatory patterns. To address these questions, we are using a combination of cell biological, biochemical, biophysical, genetic, structural, and bioinformatic approaches. Our studies focus primarily on the model organism Caulobacter crescentus, a Gram-negative bacterium that is characterized by its unique developmental cycle. In addition, we have extended our work to alternative model systems to facilitate comparative studies
Cells of C. crescentus can easily be synchronized and then be observed as they progress synchronously through the developmental cycle, which greatly facilitates the study of cell cycle-dependent processes. Moreover, owing to its asymmetric cellular layout and its division into two morphologically and physiologically distinct daughter cells, C. crescentus represents an attractive model for studying bacterial differentiation.
Positioning and function of the cell division apparatus
Bacterial cytokinesis is usually mediated by a ring-shaped multi-protein complex, called the divisome. Its function needs to be closely coordinated with DNA replication and segregation to ensure that separation of the incipient daughter cells occurs precisely in between the two newly synthesized sister chromosomes. Moreover, the different components of the divisome have to assemble and interact in a tightly regulated manner to facilitate coordinated invagination of the different cell envelope layers.
n C. crescentus, positioning of the division apparatus is achieved by a delicate interplay of dynamic protein complexes, which ultimately gives rise to a bipolar gradient of the division inhibitor MipZ that restricts divisome assembly to midcell. Our group investigates the molecular mechanisms that underlie this unique regulatory system. Another focal point of interest is the function of the division apparatus itself. To dissect the division process, we are studying the composition of the C. crescentus divisome and investigating the role of known and newly identified components.
Cytoskeleton, cell polarity, and morphogenesis
The internal polarity of C. crescentus cells is manifested by the development of two different daughter cells that differ in cell size, shape, and the complement of cellular appendages. Cell polarization involves both the cytoskeleton and localized regulatory proteins. We have recently identified a novel and highly conserved cytoskeletal protein, termed bactofilin, which serves as a polar localization factor for cell wall biosynthetic enzymes involved in stalk biogenesis. We are currently investigating the dynamics and biological function of bactofilin homologues in various model systems. Moreover, we have a general interest in bacterial morphogenesis, with a focus on the mechanisms responsible for remodeling of the cell wall during growth, division, and cell differentiation.
Research area: Cellular differentiation and cell division in bacteria
In recent years, advances in microbial cell biology have led to a fundamental change in the perception of bacteria. While previously envisioned as membrane-bounded conglomerates of enzymes, bacterial cells have now emerged to be highly organized entities that tightly regulate cell shape and polarity, actively segregate plasmids and chromosomal DNA, and frequently undergo complex differentiation processes. As in eukaryotes, their temporal and spatial organization is controlled by multi-component regulatory networks, involving localized protein complexes and dynamic cytoskeletal structures. However, despite the progress made, the current knowledge on cellular organization in bacteria is still very limited, providing ample opportunities for future research.