Spatiotemporal Model of the Asymmetric Division Cycle of Caulobacter crescentus

The life cycle of Caulobacter crescentus is of interest because of the asymmetric nature of cell division that gives rise to progeny that have distinct morphology and function. One daughter called the stalked cell is sessile and capable of DNA replication, while the second daughter called the swarmer cell is motile but quiescent. Advances in microscopy combined with molecular biology techniques have revealed that macromolecules are localized in a non-homogeneous fashion in the cell cytoplasm, and that dynamic localization of proteins is critical for cell cycle progression and asymmetry. However, the molecular-level mechanisms that govern protein localization, and enable the cell to exploit subcellular localization towards orchestrating an asymmetric life cycle remain obscure. There are also instances of researchers using intuitive reasoning to develop very different verbal explanations of the same biological process. To provide a complementary view of the molecular mechanism controlling the asymmetric division cycle of Caulobacter, we have developed a mathematical model of the cell cycle regulatory network. Our reaction-diffusion models provide additional insight into specific mechanism regulating different aspects of the cell cycle. We describe a molecular mechanism by which the bifunctional histidine kinase PleC exhibits bistable transitions between phosphatase and kinase forms. We demonstrate that the kinase form of PleC is crucial for both swarmer-to-stalked cell morphogenesis, and for replicative asymmetry in the predivisional cell. We propose that localization of the scaffolding protein PopZ can be explained by a Turing-type mechanism. Finally, we discuss a preliminary model of ParA- dependent chromosome segregation. Our model simulations are in agreement with experimentally observed protein distributions in wild-type and mutant cells. In addition to predicting novel mutants that can be tested in the laboratory, we use our models to reconcile competing hypotheses and provide a unified view of the regulatory mechanisms that direct the Caulobacter cell cycle.

Name thesis:degree_name

Ph. D.

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Genetics, Bioinformatics, and Computational Biology

Department dc:contributor.department

Animal and Poultry Sciences

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2014

Author dc:creator

• Subramanian, Kartik

Chairs dc:contributor.committeechair

• Tyson, John J.
• Paul, Mark R.

Committee members dc:contributor.committeemember

• Scharf, Birgit E.
• Cao, Yang

• Mathematical modeling
• Caulobacter cell cycle
• protein regulatory networks
• reaction-diffusion models

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Dc Identifier Other

vt_gsexam:3759

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/65156