17. Molecular titration generates ultrasensitive responses in biological circuits¶

Design principle

Molecular titration provides a simple, versatile mechanism to generate ultrasensitive responses in molecular circuits
Molecular titration enables stochastic activation of bacterial persistence states

Techniques

Stochastic simulation
Separation of timescales

Papers

N.E. Buchler and F.R. Cross, Protein sequestration generates a flexible ultrasensitive response in a genetic network, Mol. Syst. Biol. (2009).
Kim J, White KS, and Winfree E, Construction of an in vitro bistable circuit from synthetic transcriptional switches, Molecular Systems Biology (2006).
Cuba Samaniego C et al, Molecular Titration Promotes Oscillations and Bistability in Minimal Network Models with Monomeric Regulators, ACS Synthetic Biology (2016).
1. Mukherji et al, “MicroRNAs can generate thresholds in target gene expression”, Nat. Gen. 2011
Levine et al, PLoS Biol, 2007; Mukherji et al, 2011: Regulation of mRNA level by small RNAs
1. Rotem et al, Regulation of phenotypic variability by a threshold- based mechanism underlies bacterial persistence, PNAS 2010.
Koh RS and Dunlop MJ, Modeling suggests that gene circuit architecture controls phenotypic variability in a bacterial persistence network, BMC Systems Biology, 2012
Ferrell JE Jr and Ha SH wrote a three-part series of articles on ultrasensitivity: See parts I, II, and III. All are excellent, but part II in particular covers stoichiometric inhibitors, which is the main focus of this lecture.

[1]:

import numpy as np
import scipy.stats as st
import numba
import collections


import biocircuits
import panel as pn
pn.extension()


import bokeh.io
import bokeh.plotting

bokeh.io.output_notebook()