Distributed Delay Improves the Dynamics of Gene Regulation

Gene Regulatory Networks (GRNs) are the principal decision-making apparatuses of cells. GRNs play a critical role in a diverse array of biological processes; cell-fate determination in embryonic development, the induction of labor at the end of pregnancy, maintenance of circadian rhythms, the onset of puberty, quorum sensing in bacteria, and preventing cells from becoming cancerous are some examples of what GRNs do. A critical feature that governs the dynamics of GRNs is the delay between the start of transcription of a gene and the formation of a functional protein. Indeed, any model of Gene Regulation must account for this delay in some way in order to be useful. But the molecular mechanisms in a cell are subject to stochasticity, making this delay inherently random. Through a combination of computer simulation and explanatory modeling, this dissertation demonstrates the counterintuitive advantages that arise from the presence of stochasticity in transcriptional delay. In particular, for negative feedback architectures, genetic oscillators, distributed delay increases the signal-to-noise ratio of the oscillatory signal and reduces resource utilization to maintain stable oscillations, and for positive feedback architectures, bistable toggles, distributed delay increases mean residency times.

Name thesis:degree_name

Doctor of Philosophy

Discipline thesis:degree_discipline

Mathematics

Grantor

University of Houston

Year dc:date.issued

2025

Author dc:creator

• Campbell, Sean Paul 1994-

Advisor dc:contributor.advisor

• Ott, William

Committee members dc:contributor.committeemember

• Timofeyev, Ilya
• Azevedo, Ricardo
• Perepelitsa, Mikhail

• Molecular biology
• Mathematics

Language dc:language.iso

English

Handle dc:identifier.uri

https://hdl.handle.net/10657/20685

OAI identifier oai:identifier

oai:uh-ir.tdl.org:10657/20685