Theses and Dissertations at Montana State University (MSU)
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Item Quantifying robustness of the gap gene network(Montana State University - Bozeman, College of Letters & Science, 2024) Andreas, Elizabeth Anne; Chairperson, Graduate Committee: Tomas Gedeon; Bree Cummins (co-chair)Early development of Drosophila melanogaster (fruit fly) facilitated by the gap gene network has been shown to be incredibly robust, and the same patterns emerge even when the process is seriously disrupted. We investigate this robustness using a previously developed computational framework called DSGRN (Dynamic Signatures Generated by Regulatory Networks). Our mathematical innovations include the conceptual extension of this established modeling technique to enable modeling of spatially monotone environmental effects, as well as the development of a collection of graph theoretic robustness scores for network models. This allows us to rank order the robustness of network models of cellular systems where each cell contains the same genetic network topology but operates under a parameter regime that changes continuously from cell to cell. We demonstrate the power of this method by comparing the robustness of two previously introduced network models of gap gene expression along the anterior-posterior axis of the fruit fly embryo, both to each other and to a random sample of networks with same number of nodes and edges. We observe that there is a substantial difference in robustness scores between the two models. Our biological insight is that random network topologies are in general capable of reproducing complex patterns of expression, but that using measures of robustness to rank order networks permits a large reduction in hypothesis space for highly conserved systems such as developmental networks.Item Gene regulation in the lac operon(Montana State University - Bozeman, College of Letters & Science, 2009) Patterson, Kathryn Grace; Chairperson, Graduate Committee: Tomas GedeonThe lac operon, a jointly controlled series of genes in the bacteria E. coli, has been studied extensively since the 1940's. The lac operon genes are transcribed and then translated into proteins necessary for transport and digestion of lactose. The operon is activated in the presence of lactose after glucose, the preferred carbon source, has been expended. In this thesis, we introduce a biophysical model using the Shea-Ackers framework for modeling promoter dynamics. The model spans two scales: the inputs are biophysical parameters of molecular interactions and the result is a level of gene expression - a macroscopic behavior of the cell. We include all experimentally suggested control mechanisms into the model, even though the experimental evidence is stronger for some of these mechanisms than others. We compare our model to experimental data and explore the individual contribution of the proposed mechanisms by removing them one by one and testing the reduced model's fit to the data. Finally, we find a minimal model which faithfully represents the available data, yet includes only the minimal number of control mechanisms.