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Browsing by Author "Arat, Seda"

Now showing 1 - 4 of 4
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    A Mathematical Model of a Denitrification Metabolic Network in Pseudomonas aeruginosa
    Arat, Seda (Virginia Tech, 2012-11-30)
    Lake Erie, one of the Great Lakes in North America, has witnessed recurrent summertime low oxygen dead zones for decades. This is a yearly phenomenon that causes microbial production of the greenhouse gas nitrous oxide from denitrification. Complete denitrification is a microbial process of reduction of nitrate to nitrogen gas via nitrite, nitric oxide, and greenhouse gas nitrous oxide. After scanning the microbial community in Lake Erie, Pseudomonas aeruginosa is decided to be examined, not because it is abundant in Lake Erie, but because it can perform denitrification under anaerobic conditions. This study focuses on a mathematical model of the metabolic network in Pseudomonas aeruginosa under denitrification and testable hypotheses generation using polynomial dynamical systems and stochastic discrete dynamical systems. Analysis of the long-term behavior of the system changing the concentration level of oxygen, nitrate, and phosphate suggests that phosphate highly affects the denitrification performance of the network.
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    Modeling stochasticity and variability in gene regulatory networks
    Murrugarra, David; Veliz-Cuba, Alan; Aguilar, Boris; Arat, Seda; Laubenbacher, Reinhard C. (2012-06-06)
    Modeling stochasticity in gene regulatory networks is an important and complex problem in molecular systems biology. To elucidate intrinsic noise, several modeling strategies such as the Gillespie algorithm have been used successfully. This article contributes an approach as an alternative to these classical settings. Within the discrete paradigm, where genes, proteins, and other molecular components of gene regulatory networks are modeled as discrete variables and are assigned as logical rules describing their regulation through interactions with other components. Stochasticity is modeled at the biological function level under the assumption that even if the expression levels of the input nodes of an update rule guarantee activation or degradation there is a probability that the process will not occur due to stochastic effects. This approach allows a finer analysis of discrete models and provides a natural setup for cell population simulations to study cell-to-cell variability. We applied our methods to two of the most studied regulatory networks, the outcome of lambda phage infection of bacteria and the p53-mdm2 complex.
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    A Network Biology Approach to Denitrification in Pseudomonas aeruginosa
    Arat, Seda; Bullerjahn, George S.; Laubenbacher, Reinhard C. (2015-02-23)
    Pseudomonas aeruginosa is a metabolically flexible member of the Gammaproteobacteria. Under anaerobic conditions and the presence of nitrate, P. aeruginosa can perform (complete) denitrification, a respiratory process of dissimilatory nitrate reduction to nitrogen gas via nitrite (NO₂), nitric oxide (NO) and nitrous oxide (N₂O). This study focuses on understanding the influence of environmental conditions on bacterial denitrification performance, using a mathematical model of a metabolic network in P. aeruginosa. To our knowledge, this is the first mathematical model of denitrification for this bacterium. Analysis of the long-term behavior of the network under changing concentration levels of oxygen (O₂), nitrate (NO₃), and phosphate (PO₄) suggests that PO₄ concentration strongly affects denitrification performance. The model provides three predictions on denitrification activity of P. aeruginosa under various environmental conditions, and these predictions are either experimentally validated or supported by pertinent biological literature. One motivation for this study is to capture the effect of PO₄ on a denitrification metabolic network of P. aeruginosa in order to shed light on mechanisms for greenhouse gas N₂O accumulation during seasonal oxygen depletion in aquatic environments such as Lake Erie (Laurentian Great Lakes, USA). Simulating the microbial production of greenhouse gases in anaerobic aquatic systems such as Lake Erie allows a deeper understanding of the contributing environmental effects that will inform studies on, and remediation strategies for, other hypoxic sites worldwide.
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    A Systems Biology Approach to Microbiology and Cancer
    Arat, Seda (Virginia Tech, 2015-09-03)
    Systems biology is an interdisciplinary field that focuses on elucidating complex biological processes (systems) by investigating the interactions among its components through an iterative cycle composed of data generation, data analysis and mathematical modeling. Our contributions to systems biology revolve around the following two axes: - Data analysis: Two data analysis projects, which were initiated when I was a co-op at GlaxoSmithKline, are discussed in this thesis. First, next generation sequencing data generated for a phase I clinical trial is analyzed to determine the altered microbial community in human gut before and after antibiotic usage (Chapter 2). To our knowledge, there have not been similar comparative studies in humans on the impacts on the gut microbiome of an antibiotic when administered by different modes. Second, publicly available gene expression data is analyzed to investigate human immune response to tuberculosis (TB) infection (Chapter 3). The novel feature of this study is systematic drug repositioning for the prevention, control and treatment of TB using the Connectivity map. - Mathematical modeling: Polynomial dynamical systems, a state- and time- discrete logical modeling framework, is used to model two biological processes. First, a denitrification pathway in Pseudomonas aeruginosa is modeled to shed light on the reason of greenhouse gas nitrous oxide accumulation (Chapter 4). It is the first mathematical model of denitrification that can predict the effect of phosphate on the denitrification performance of this bacterium. Second, an iron homeostasis pathway linked to iron utilization, oxidative stress response and oncogenic pathways is constructed to investigate how normal breast cells become cancerous (Chapter 5). To date, our intracellular model is the only expanded core iron model that can capture a breast cancer phenotype by overexpression and knockout simulations.