Mathematical Models For Processes in Bacterial Cell Division

Rensselaer Polytechnic Institute, Troy NY

Investigators

Abstract

Drew 0214585 The investigator derives and studies mathematical models for several different processes involved with cell division, focusing on E. coli cells because of the wealth of data available. A mature cell replicates its DNA. The daughter DNA strands must move into the halves of the mature cell, and finally, the cell divides. The relative timing of these events is crucial for the division into viable daughter cells, and placement of the septum must divide the cell and its DNA into relatively equal halves. Once replication begins,the cell then must become unable to start replication again until the cell is sufficiently mature. Sequestration is responsible for this eclipse period, where the new DNA strand binds to sites in the membrane, thereby blocking the oriC site and dnaA transcription regulation site, keeping the replication initiation from occurring too soon. This process of sequestration and de-sequestration is therefore (at least partially) responsible for the timing of cell division events. The mathematical model predicts the probability of each of the sequestration sites being sequestered, as a function of time. The replicated DNA strands are moved apart in the longitudinal direction (towards the cell poles) in order to assure exactly one set of chromosomes in each daughter cell. The process by which this occurs is unknown, but the timing of this event is crucial to viability. The project studies viable models for this seqregation. The site for septation is marked by formation of a Z-ring at the center of the rod-shaped cell, halfway between the poles. This Z-ring is involved in causing the cell to form a septum between the daughter halves. Placement of the Z-ring at the center is a result of the cooperative actions of three proteins from the min locus of the DNA. Three proteins behave in an oscillatory manner, with MinD alternately forming a layer on the cell membrane near one pole, then disassembling and re-forming at the other pole. The investigator studies a model for the dynamics of the Min system. The investigaor develops mathematical models to improve the understanding of the biology of cell division in E. coli. The basic philosophy is to determine mechanisms that can describe observed events, and to evaluate whether these mechanisms can operate for reasonable parameter values, that is, whether the kinetic rates, diffusivities, and concentrations are within reasonable ranges of observed values. Location and timing of cellular events is an important aspect of molecular biology. Moreover, mathematical models that incorporate intracellular transport and reactions, including reactions with organelles, should prove to be of general applicability to cellular biology. Such models can focus biological research on aspects of molecular dynamics that otherwise seem unconnected.