Kolomeisky, Anatoly B2020-04-232020-04-232020-052020-04-22May 2020Klindziuk, Alena. "Theoretical Investigations of Transcriptional Bursting." (2020) Master’s Thesis, Rice University. <a href="https://hdl.handle.net/1911/108359">https://hdl.handle.net/1911/108359</a>.https://hdl.handle.net/1911/108359Transcriptional bursting, or the random alternation between periods of synthesis of messenger RNA molecules and cessation of the transfer of genetic information, is present in all cell types and is an important contributing factor to gene expression noise. Yet, its exact molecular mechanisms remain unclear. In response to an experimental observation that certain transcription systems have a spectrum of activity levels, we developed a phenomenological multi-state theoretical model of transcription. By solving the model exactly and analyzing the results, we found that the degree of stochastic fluctuations during transcription directly correlates with the number of independent biochemical states in the system. In response to studies that show that supercoiling plays an important role in bacterial transcription, we developed a more microscopic mechano-chemical model of transcription. Solving the model, we demonstrate that the interplay between chemical process of RNA synthesis and mechanical stress build up on the DNA strand can lead to transcriptional bursting dynamics. Also, the first-passage analysis was used to estimate the energy to produce an RNA when supercoiling is at play.application/pdfengCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.transcriptiongene expressionThesis2020-04-23