Functional States of the Genome-Scale Escherichia Coli Transcriptional Regulatory System
A transcriptional regulatory network (TRN) constitutes the collection of regulatory rules that link environmental cues to the transcription state of a cell’s genome. We recently proposed a matrix formalism that quantitatively represents a system of such rules (a transcriptional regulatory system [TRS]) and allows systemic characterization of TRS properties. The matrix formalism not only allows […]
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Proteomic and network analysis characterize stage-specific metabolism in Trypanosoma cruzi
Background: Trypanosoma cruzi is a Kinetoplastid parasite of humans and is the cause of Chagas disease, a potentially lethal condition affecting the cardiovascular, gastrointestinal, and nervous systems of the human host. Constraint-based modeling has emerged in the last decade as a useful approach to integrating genomic and other high-throughput data sets with more traditional, experimental […]
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Dynamic Analysis of Integrated Signaling, Metabolic, and Regulatory Networks
Extracellular cues affect signaling, metabolic, and regulatory processes to elicit cellular responses. Although intracellular signaling, metabolic, and regulatory networks are highly integrated, previous analyses have largely focused on independent processes (e.g., metabolism) without considering the interplay that exists among them. However, there is evidence that many diseases arise from multifunctional components with roles throughout signaling, […]
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Systems analysis of metabolism in the pathogenic trypanosomatid Leishmania major
Systems analyses have facilitated the characterization of metabolic networks of several organisms. We have reconstructed the metabolic network of Leishmania major, a poorly characterized organism that causes cutaneous leishmaniasis in mammalian hosts. This network reconstruction accounts for 560 genes, 1112 reactions, 1101 metabolites and 8 unique subcellular localizations. Using a systems- based approach, we hypothesized […]
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Predicting biological system objectives de novo from internal state measurements
Background: Optimization theory has been applied to complex biological systems to interrogate network properties and develop and refine metabolic engineering strategies. For example, methods are emerging to engineer cells to optimally produce byproducts of commercial value, such as bioethanol, as well as molecular compounds for disease therapy. Flux balance analysis (FBA) is an optimization framework […]
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Multiscale computational analysis of Xenopus laevis morphogenesis reveals key insights of systems-level behavior
Background: Tissue morphogenesis is a complex process whereby tissue structures self-assemble by the aggregate behaviors of independently acting cells responding to both intracellular and extracellular cues in their environment. During embryonic development, morphogenesis is particularly important for organizing cells into tissues, and although key regulatory events of this process are well studied in isolation, a […]
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Systems analyses characterize integrated functions of biochemical networks
Metabolic, regulatory and signaling pathways have been characterized in detail over the past century. As the amount of genomic, proteomic and metabolic data has increased, and the mathematical and analytical capabilities of interrogating these data have advanced, the overlapping roles of pathway constituents have been described. These developments reflect the truly integrated nature of subcellular […]
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Reconstruction of Cellular Signalling Networks and Analysis of Their Properties
The study of cellular signalling over the past 20 years and the advent of high- throughput technologies are enabling the reconstruction of large-scale signalling networks. After careful reconstruction of signalling networks, their properties must be described within an integrative framework that accounts for the complexity of the cellular signalling network and that is amenable to […]
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Multicellular computer simulation of morphogenesis: blastocoel roof thinning and matrix assembly in Xenopus laevis
In the blastocoel roof (BCR) of the Xenopus laevis embryo, epibolic movements are driven by the radial intercalation of deep cell layers and the coordinate spreading of the overlying superficial cell layer. Thinning of the lateral margins of the BCR by radial intercalation requires fibronectin (FN), which is produced and assembled into fibrils by the […]
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The Roles of APC and Axin Derived Analysis of the Wnt Pathway
Wnt signaling plays an important role in both oncogenesis and development. Activation of the Wnt pathway results in stabilization of the transcriptional coactivator b-catenin. Recent studies have demonstrated that axin, which coordinates b-catenin degradation, is itself degraded. Although the key molecules required for transducing a Wnt signal have been identified, a quantitative understanding of this […]
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