Browsing by Author "Brazhnik, Paul"

Now showing 1 - 3 of 3
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    Mathematical Models of Some Signaling Pathways Regulating Cell Survival and Death
    Zhang, Tongli (Virginia Tech, 2008-10-23)
    In a multi-cellular organism, cells constantly receive signals on their internal condition and surrounding environment. In response to various signals, cells proliferate, move around or even undergo suicide. The signal-response is controlled by complex molecular machinery, understanding of which is an important goal of basic molecular biological research. Such understanding is also valuable for clinical application, since lethal diseases like cancer show maladaptive responses to growth-regulating signals. Because the multiple feedbacks in the molecular regulatory machinery obscure cause-effect relations, it is hard to understand these control systems by intuition alone. Here we translate the molecular interactions into differential equations and recapture the cellular physiological properties with the help of numerical simulations and non-linear dynamical tools. The models address the physiological features of programmed cell death, the cell fate decision by p53 and the dynamics of the NF-?B control system. These models identify key molecular interactions responsible for the observed physiological properties, and they generate experimentally testable predictions to validate the assumptions made in the models.
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    Quantitative Modeling of the Molecular Mechanism Controlling the Asymmetric Cell Division Cycle in Caulobacter crescentus
    Li, Shenghua (Virginia Tech, 2008-10-24)
    Caulobacter crescentus is an important model organism for studying regulation of cell growth, division and differentiation in prokaryotes. C. crescentus undergoes asymmetric division producing two progeny cells with identical genome but different developmental programs: the "swarmer" cell is flagellated and motile, and the "stalked" cell is sessile (attached to a surface by its stalk and holdfast). Only stalked cells undergo chromosome replication and cell division. A swarmer cell must shed its flagellum and grow a stalk before it can enter the replication-division cycle. Based on published experimental evidence, we propose a molecular mechanism controlling the cell division cycle in this bacterium. Our quantitative model of the mechanism illustrates detailed temporal dynamics of regulatory proteins and corresponding physiological changes during the process of cell cycle progression and differentiation of wild-type cells (both stalked cells and swarmer cells) and of a number of known and novel mutant strains. Our model presents a unified view of temporal regulation of protein activities during the asymmetric cell division cycle of C. crescentus and provides an opportunity to study and analyze the system dynamics of the Caulobacter cell cycle (as opposed to the dynamics of individual steps). The model can serve as a starting point for investigating molecular regulations of cell division and differentiation in other genera of alpha-proteobacteria, such as Brucella and Rhizobium, because recent experimental data suggest that these alpha-proteobacteria share similar genetic mechanisms for cell cycle control.
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    Synchronization between Attractors: Genomic Mechanism of Cell-Fate Change
    Tsuchiya, Masa; Brazhnik, Paul; Bizzarri, Mariano; Giuliani, Alessandro (MDPI, 2023-07-18)
    Herein, we provide a brief overview of complex systems theory approaches to investigate the genomic mechanism of cell-fate changes. Cell trajectories across the epigenetic landscape, whether in development, environmental responses, or disease progression, are controlled by extensively coordinated genome-wide gene expression changes. The elucidation of the mechanisms underlying these coherent expression changes is of fundamental importance in cell biology and for paving the road to new therapeutic approaches. In previous studies, we pointed at dynamic criticality as a plausible characteristic of genome-wide transition dynamics guiding cell fate. Whole-genome expression develops an engine-like organization (genome engine) in order to establish an autonomous dynamical system, capable of both homeostasis and transition behaviors. A critical set of genes behaves as a critical point (CP) that serves as the organizing center of cell-fate change. When the system is pushed away from homeostasis, the state change that occurs at the CP makes local perturbation spread over the genome, demonstrating self-organized critical (SOC) control of genome expression. Oscillating-Mode genes (which normally keep genome expression on pace with microenvironment fluctuations), when in the presence of an effective perturbative stimulus, drive the dynamics of synchronization, and thus guide the cell-fate transition.