Morris LMU Symposium Spring 2016

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Mathematical Modeling Shows that Gln3 Affects the Dynamics of the Gene Regulatory Network Controlling the Cold Shock Response in Saccharomyces cerevisiae

Tessa A. Morris, Kristen M. Horstmann, Brandon Klein, Ben G. Fitzpatrick, Kam D. Dahlquist Affiliations: Department of Biology, Loyola Marymount University

A gene regulatory network (GRN) consists of a set of transcription factors that regulate the expression of genes encoding other transcription factors. The focus of this study was to determine the GRN that controls the cold shock response in budding yeast, Saccharomyces cerevisiae, and to model its dynamics. Microarray experiments were performed in the Dahlquist lab to measure gene expression after 15, 30, and 60 minutes of cold shock for both the wild type strain and a strain deleted for the transcription factor Gln3. These data were used as input to a MATLAB software package called GRNmap, which uses ordinary differential equations to model the dynamics of a medium-scale gene regulatory network. The program estimates production rates, expression thresholds, and regulatory weights for each transcription factor in the network using a penalized least squares approach. A modified ANOVA showed that 1356 genes (22%) had a log2 fold change significantly different than zero with an adjusted p value of < 0.05 for at least one timepoint for the Gln3 deletion strain. These genes were submitted to the YEASTRACT database to determine the transcription factors that regulate them. From this, a family of 49 GRNs ranging from 35 genes and 120 edges to 14 genes and 26 edges was generated. Parameter values, production rates, regulatory weights, and expression thresholds were compared for each of these GRNs. These results show that the presence or absence of Gln3 affects the dynamics of the gene regulatory network controlling the cold shock response in yeast.

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