Dissertation
Antisense transcriptional interference leads to bistability and hysteresis in β:α myosin heavy chain switch
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Spring 2026
DOI: 10.25820/etd.008437
Abstract
A key marker of pathological cardiac hypertrophy is the shift in the ratio between the expression of myosin heavy chain 6 (Myh6) and myosin heavy chain 7 (Myh7). Healthy adult hearts exhibit a lower Myh7:Myh6 ratio, while adult hearts in heart failure exhibit a higher ratio. The key regulatory RNA in this system is Mhrt (“My-heart”), a long noncoding RNA transcribed from within the Myh7 locus. This project aims to model the interaction between Myh6, Myh7, and Mhrt to gain a better understanding of the switch between Myh6 and Myh7. We begin by investigating the shared divergent promoter of Myh6 and Mhrt and its interaction with the regulatory protein BRG1. Then we use a Monte-Carlo simulation to approximate the probability of successful transcription for antisense Mhrt and Myh7. Finally, we combine the two results in a system of stochastic ordinary differential equations and perform a bifurcation analysis to better understand the Myh6-Myh7 switch and its relationship to heart disease.
Details
- Title: Subtitle
- Antisense transcriptional interference leads to bistability and hysteresis in β:α myosin heavy chain switch
- Creators
- Claire A. Christian
- Contributors
- Colleen Mitchell (Advisor)Chad Grueter (Committee Member)Bruce Ayati (Committee Member)Isabel Darcy (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Mathematics
- Date degree season
- Spring 2026
- DOI
- 10.25820/etd.008437
- Publisher
- University of Iowa
- Number of pages
- xii, 113 pages
- Copyright
- Copyright 2026 Claire A. Christian
- Language
- English
- Date submitted
- 04/21/2026
- Description illustrations
- Illustrations, graphs, charts, tables
- Description bibliographic
- Includes bibliographical references (pages 111-113).
- Public Abstract (ETD)
Heart disease is associated with a shift in the balance between expression of myosin heavy chains 6 and 7 (Myh6 and Myh7), which are essential for proper heart functions. Healthy hearts maintain one balance while diseased hearts shift toward increased Myh7 expression. This change is influenced by a regulatory RNA called Mhrt (“My-heart”). In this project we use mathematical modeling to study how interactions between Myh6, Myh7, Mhrt, and the regulatory protein BRG1 drive this shift. This work provides insight into the mechanisms underlying heart disease and demonstrates how mathematical models can help explain complex biological processes.
- Academic Unit
- Mathematics
- Record Identifier
- 9985177273302771
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