Mathematical Models For Processes in Bacterial Cell Division

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Drew0214585 The investigator derives and studies mathematical models forseveral different processes involved with cell division, focusingon E. coli cells because of the wealth of data available. Amature cell replicates its DNA. The daughter DNA strands mustmove into the halves of the mature cell, and finally, the celldivides. The relative timing of these events is crucial for thedivision into viable daughter cells, and placement of the septummust divide the cell and its DNA into relatively equal halves.Once replication begins,the cell then must become unable to startreplication again until the cell is sufficiently mature.Sequestration is responsible for this eclipse period, where thenew DNA strand binds to sites in the membrane, thereby blockingthe oriC site and dnaA transcription regulation site, keeping thereplication initiation from occurring too soon. This process ofsequestration and de-sequestration is therefore (at leastpartially) responsible for the timing of cell division events.The mathematical model predicts the probability of each of thesequestration sites being sequestered, as a function of time. Thereplicated DNA strands are moved apart in the longitudinaldirection (towards the cell poles) in order to assure exactly oneset of chromosomes in each daughter cell. The process by whichthis occurs is unknown, but the timing of this event is crucialto viability. The project studies viable models for thisseqregation. The site for septation is marked by formation of aZ-ring at the center of the rod-shaped cell, halfway between thepoles. This Z-ring is involved in causing the cell to form aseptum between the daughter halves. Placement of the Z-ring atthe center is a result of the cooperative actions of threeproteins from the min locus of the DNA. Three proteins behave inan oscillatory manner, with MinD alternately forming a layer onthe cell membrane near one pole, then disassembling andre-forming at the other pole. The investigator studies a modelfor the dynamics of the Min system. The investigaor develops mathematical models to improve theunderstanding of the biology of cell division in E. coli. Thebasic philosophy is to determine mechanisms that can describeobserved events, and to evaluate whether these mechanisms canoperate for reasonable parameter values, that is, whether thekinetic rates, diffusivities, and concentrations are withinreasonable ranges of observed values. Location and timing ofcellular events is an important aspect of molecular biology.Moreover, mathematical models that incorporate intracellulartransport 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 moleculardynamics that otherwise seem unconnected.