Horstmann Klein Morris Abstract

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Mathematical Modeling Reveals Zap1's Role in the Gene Regulatory Network that Controls the Response to Cold Shock in Saccharomyces cerevisiae

Transcription factors are proteins that act together in a gene regulatory network (GRN) by repressing or activating the expression of target genes. The purpose of this study is to determine the GRN for Saccharomyces cerevisiae, budding yeast, that controls the response to cold shock. The Dahlquist Lab has conducted DNA microarray experiments to measure gene expression after 15, 30, and 60 minutes of cold shock treatment for the wild type strain and a strain deleted for the Zap1 transcription factor. 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 2559 genes (41%) had a log2 fold change significantly different than zero with an adjusted p value of < 0.05 for at least one timepoint for the Zap1 deletion strain. These genes were submitted to the YEASTRACT database to determine the transcription factors that regulate them. From this, a family of GRNs ranging from 34 genes and 98 edges to 15 genes and 27 edges was generated. Parameter values, production rates, regulatory weights, and expression thresholds were compared for each of these GRNs. From the modeling of the network families, we have observed that Zap1 plays an important role in the gene regulatory network that controls cold shock response in Saccharomyces cerevisiae.

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