Browsing by Author "Sevier, Stuart A."

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    Modeling delayed processes in biological systems
    (American Physical Society, 2016) Feng, Jingchen; Sevier, Stuart A.; Huang, Bin; Jia, Dongya; Levine, Herbert; Center for Theoretical Biological Physics
    Delayed processes are ubiquitous in biological systems and are often characterized by delay differential equations (DDEs) and their extension to include stochastic effects. DDEs do not explicitly incorporate intermediate states associated with a delayed process but instead use an estimated average delay time. In an effort to examine the validity of this approach, we study systems with significant delays by explicitly incorporating intermediate steps. We show that such explicit models often yield significantly different equilibrium distributions and transition times as compared to DDEs with deterministic delay values. Additionally, different explicit models with qualitatively different dynamics can give rise to the same DDEs revealing important ambiguities. We also show that DDE-based predictions of oscillatory behavior may fail for the corresponding explicit model.
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    Properties of cooperatively induced phases in sensing models
    (American Physical Society, 2015) Sevier, Stuart A.; Levine, Herbert; Center for Theoretical Biological Physics
    A large number of eukaryotic cells are able to directly detect external chemical gradients with great accuracy and the ultimate limit to their sensitivity has been a topic of debate for many years. Previous work has been done to understand many aspects of this process but little attention has been paid to the possibility of emergent sensing states. Here we examine how cooperation between sensors existing in a two-dimensional network, as they do on the cell's surface, can both enhance and fundamentally alter the response of the cell to a spatially varying signal. We show that weakly interacting sensors linearly amplify the cell's response to an external gradient while a network of strongly interacting sensors form a collective nonlinear response with two separate domains of active and inactive sensors forming what have called a “1/2-state.” In our analysis we examine the cell's ability to sense the direction of a signal and pay special attention to the substantially different behavior realized in the strongly interacting regime.
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    Properties of gene expression and chromatin structure with mechanically regulated elongation
    (Oxford University Press, 2018) Sevier, Stuart A.; Levine, Herbert
    In recent years, physical elements of transcription have emerged as central in our understanding of gene expression. Recent work has been done introducing a simple description of the basic physical elements of transcription where RNA elongation, RNA polymerase (RNAP) rotation and DNA supercoiling are coupled (1). Here we generalize this framework to accommodate the behavior of many RNAPs operating on multiple genes on a shared piece of DNA. The resulting framework is combined with well-established stochastic processes of transcription resulting in a model which characterizes the impact of the mechanical properties of transcription on gene expression and DNA structure. Transcriptional bursting readily emerges as a common phenomenon with origins in the geometric nature of the genetic system and results in the bounding of gene expression statistics. Properties of a multiple gene system are examined with special attention paid to the role that genome composition (gene orientation, size and intergenic distance) plays in the ability of genes to transcribe. The role of transcription in shaping DNA structure is examined and the possibility of transcription driven domain formation is discussed.