{ "cells": [ { "cell_type": "markdown", "metadata": {}, "source": [ "# Problem 3.3: Autoactivation, bistability, and the importance of leakage\n", "\n", "
" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "In this problem, we will explore a very simple circuit: autoactivation of a single gene, shown in the figure below. We will assume a separation of time scales in mRNA and protein degradation/dilution such that we only need to consider the dynamics of the protein, and we will call its concentration $x$. We will further assume that the autoactivation effect can be modeled as a Hill function with Hill coefficient $n$.\n", "\n", "
\n", "\n", "![autoactivator](autoactivator.png)\n", "\n", "
\n", "\n", "**a)** Write down an ODE describing the dynamics of $x$. Include leakage parametrized by $\\alpha$. (This is the same model for an autoactivating circuit we used in the chapter, but now including leakage.)\n", "\n", "**b)** Show that in the absence of ultrasensitivity ($0 < n \\le 1$), only one steady state exists for $\\alpha > 0$. Show further that when $\\alpha = 0$, two steady states may exist, and when they do exists, only one is stable and the stable one has $x > 0$.\n", "\n", "**c)** In part (b), we considered the case where activation is not ultrasensitive. We now consider the other extreme, where activation is infinitely ultrasensitive. Derive the condition for bistability when $n\\to\\infty$. In other words, for what parameter values does the circuit exhibit two stable steady states? Discuss this condition as it relates to design principles for bistability." ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "
" ] } ], "metadata": { "anaconda-cloud": {}, "kernelspec": { "display_name": "Python 3 (ipykernel)", "language": "python", "name": "python3" }, "language_info": { "codemirror_mode": { "name": "ipython", "version": 3 }, "file_extension": ".py", "mimetype": "text/x-python", "name": "python", "nbconvert_exporter": "python", "pygments_lexer": "ipython3", "version": "3.10.10" } }, "nbformat": 4, "nbformat_minor": 4 }