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Completed project:

7.2013-7.2015: Polish Ministry of Science Iuventus Plus grant 0501/IP1/2013/72
Theoretical study of conditions for precise gene regulation in a 2-gene cascade with autoregulation

In [A. Ochab-Marcinek, M. Tabaka, PNAS, 2010] we studied a theoretical model of gene expression in the simplest possible gene regulatory system: a two-step cascade with noncooperative binding of transcription factors. Such a system is deterministically monostable. We have shown that in this system bimodal gene expression is still possible: The reaction of binding of transcription factors to DNA acts as a nonlinear noise filter that transforms the unimodal distribution of transcription factors over the cell population into the bimodal distribution of proteins produced from the regulated gene. We have found a simple method based on geometric construction that allows one to predict the onset of bimodality. These findings may explain the experimentally observed bimodal response of cascades controlled by the tetracycline repressor.

In the current project, we extend our study to more complex regulatory motifs. We want to find the conditions for precise gene regulation in these systems.

Scientific papers published as the result of the project:
  1. A. Ochab-Marcinek, M. Tabaka, Transcriptional leakage versus noise: A simple mechanism of conversion between binary and graded response in autoregulated genes, Phys. Rev. E, 2015, 91(1), 012704 [arxiv preprint]
  2. J. Jędrak, A. Ochab-Marcinek, Influence of gene copy number on self-regulated gene expression, J. Theor. Biol., 408 (2016) 222 [arxiv preprint]
  3. J. Jędrak, A. Ochab-Marcinek, Time-dependent solutions for a stochastic model of gene expression with molecule production in the form of a compound Poisson process, Phys. Rev. E 94 (3) (2016) 032401 [arxiv preprint]
  4. Hill kinetics as a noise filter: The role of transcription factor autoregulation in gene cascades, Phys. Chem. Chem. Phys., 2017, 19, 22580-22591