Mathematical Models For Processes in Bacterial Cell Division

研究者推导并研究了与细胞分裂有关的几种不同过程的数学模型，由于有丰富的可用数据，他们将重点放在大肠杆菌细胞上。成熟细胞复制它的DNA。子DNA链必须进入成熟细胞的两半，最后，细胞分裂。这些事件的相对时间对于分裂成可存活的子细胞至关重要，而间隔的位置必须将细胞及其DNA分裂成相对相等的两半。一旦复制开始，细胞就必须变得无法再次开始复制，直到细胞足够成熟。隔离作用导致了这个蚀期，在这个蚀期中，新的DNA链与膜上的位点结合，从而阻断oriC位点和DNA转录调节位点，防止复制起始发生得太快。因此，这种隔离和解除隔离的过程（至少部分地）决定了细胞分裂事件的时间。数学模型预测了每个封存点被封存的概率，作为时间的函数。复制的DNA链沿着纵向（向细胞极方向）分开，以确保每个子细胞中有一组染色体。这一过程发生的过程是未知的，但这一事件的时间是至关重要的可行性。该项目研究这种分离的可行模型。在杆状细胞的中心，两极之间形成一个az环，标志着分裂的位置。这个z环参与导致细胞在子细胞之间形成无菌。z环在中心的位置是来自DNA最小位点的三个蛋白协同作用的结果。三种蛋白质以振荡的方式表现，MinD交替地在细胞膜的一极附近形成一层，然后在另一极分解和重新形成。研究者研究了Min系统的动力学模型。研究人员开发数学模型，以提高对大肠杆菌细胞分裂生物学的理解。基本原理是确定可以描述观察到的事件的机制，并评估这些机制是否可以在合理的参数值下运行，也就是说，动力学速率、扩散率和浓度是否在观测值的合理范围内。细胞事件的定位和定时是分子生物学的一个重要方面。此外，结合细胞内运输和反应的数学模型，包括与细胞器的反应，应该被证明对细胞生物学具有普遍的适用性。这样的模型可以将生物学研究集中在分子动力学的各个方面，否则这些方面似乎是不相关的。

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.