Nathan Dyjack

Date of Award

2016

Document Type

Thesis

Degree Name

Bachelors

Department

Natural Sciences

First Advisor

Yildirim, Necmettin

Area of Concentration

Applied Mathematics

Abstract

To prevent indefinite cellular response to external signals, cells utilize various adaptation mechanisms. The yeast mating-response pathway is a model cellular system that exhibits adaptation to persistent external signals. This pathway employs a mitogen-activated protein kinase (MAPK) cascade which is comprised of two wellknown negative feedback inhibitions that involve the yeast phosphatase proteins Ptp3 and Msg5. The phosphorylated form of the yeast MAPK protein Fus3 (pFus3) triggers phosphorylation of both phosphatases, but transcriptionally upregulates only Msg5. To study the biological rationale for the existence of two distinct negative feedback inhibitions acting on pFus3, we used published experimental data to develop a mathematical model which quantified the inhibitory roles of the phosphatase proteins on pFus3. Our analyses show that inhibition of pFus3 due to Ptp3 is largely independent of the signal profile, and is most impactful in the early time after pheromone induction. Conversely, the feedback inhibition due to Msg5 is highly dependent on the signal profile, and is most influential after pFus3 attains its maximum cellular abundance. Similarly, Ptp3 reduces the variation of the pFus3 dynamic in an early and consistent fashion, while the strength of the Msg5 reduction to pFus3 dispersion increases with time.

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