Integrated dynamics of temporal and spatial controls in the cell division cycle of Caulobacter crescentus

Virginia Polytechnic Institute And State University, Blacksburg VA

Investigators

Abstract

In this project, the investigators will apply the methods of nonlinear dynamics and bifurcation theory for developing a better understanding of the molecular mechanism regulating temporal and spatial dynamics of the cell division cycle in Caulobacter crescentus. The biochemical network controlling cell cycle progression in Caulobacter consists of parallel and consecutive, highly nonlinear processes, comprising positive and negative feedbacks. Many proteins of this network dynamically localize at the poles of the cell in a cell cycle-dependent manner, providing a spatial dimension to cell cycle regulation. In this project the complexity of the control system will be approached from a dynamical systems perspective, by means of mathematical modeling and computer simulation. To this end, the investigators will construct an experimentally verified, dynamical mathematical model that will describe the relevant molecular events in space and time. The model will provide a rigorous account of current intuitive ideas of bacterial cell cycle control, advance our understanding of bacterial cell division, integrate available experimental data, reconcile apparently conflicting data, identify data gaps, and suggest new experimental designs. Principles of mathematical modeling, dynamical systems theory, bifurcation theory, asymptotic analysis, and numerical computation will be used and advanced by this work. The quantitative study of the molecular mechanism controlling cell division in Caulobacter will contribute to our understanding of cell cycle regulatory mechanisms and also of a fundamental issue in developmental biology (how morphogenesis is coordinated with cell cycle progression). Comparative analysis of the molecular regulation of the cell cycle in bacteria and eukaryotes can be insightful for evolutionary biology. Recent studies have shown that many of genes and mechanisms discovered in Caulobacter are evolutionarily conserved among other members of the alpha-proteobacteria. Thus, the mechanism of cell replication in Caulobacter and the mathematical model that the investigators will develop may be extendable to the whole class of alpha-proteobacteria. Several alpha-proteobacteria (including Sinorhizobium, Agrobacterium, Rickettsia, and Brucella) have important roles in a wide range of environmental, medical and biowarfare-defense applications. Therefore, this fundamental research on Caulobacter growth, replication and differentiation may have far-reaching implications. In particular, insights gained into temporal and spatial control of gene expression and protein interactions could provide new clues for rational design of antibacterial agents. On a larger scale, this study will contribute to a conceptual understanding and mathematical description of the dynamics of living systems and to extending the quantitative transformation of molecular cell biology.