Design of a long-term memory genetic toggle switch inspired by chromatin modification circuits
Name
UkjinCDC22.pdf
Description
Accepted version
Size
861.9 KB
Format
Adobe PDF
Checksum (MD5)
60978f2e9cbf1d731988075a78d9ad4f
Author(s)
Kwon, Ukjin
Huang, Hsin-Ho
Vecchio, Domitilla Del
Date Issued
December 6, 2022
Publisher
IEEE|2022 IEEE 61st Conference on Decision and Control (CDC)
Citation
Kwon, Ukjin, Huang, Hsin-Ho and Vecchio, Domitilla Del. 2022. "Design of a long-term memory genetic toggle switch inspired by chromatin modification circuits."
Version
Author's final manuscript
Abstract
A genetic toggle switch, a bistable gene-regulatory
network, has many biotechnology applications, from environmental sensing to therapeutics. In order for a toggle switch
to be practically useful, it should be able to maintain either
of its states for a sufficiently long time. While a number of
bistable circuit designs have appeared, it remains a challenge
to control the duration of memory of the two states due to
the presence of noise. To address this problem, we propose a
bacterial toggle switch design that is inspired by a chromatin
modification circuit ubiquitous in mammalian systems. We
specifically propose a bacterial implementation based on two
DNA invertases, in which each invertase is auto-catalyzing
its own expression while also catalyzing the other invertase’s
repression. We perform a mathematical analysis of the time
to memory loss of the circuit’s stable states in a simplified
stochastic model of the system. Our analysis shows that we can
increase the time to memory loss by increasing the expression
rates of the invertases, allowing to design the circuit for longterm memory. As a comparison, we also analyze two additional
designs based on invertases, a published one, and a simpler
version of our design. We demonstrate that for these circuits,
there is no design parameter that allows to extend the time
to memory loss, thereby highlighting structural properties of
our design necessary for long-term memory. We validate the
theoretical findings by stochastic simulations of the full set
of reactions describing the circuits. More broadly, our results
provide criteria for designing long-term memory toggle switches
in bacteria.
Description
2022 IEEE 61st Conference on Decision and Control (CDC) December 6-9, 2022. Cancún, Mexico
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Terms of Use
Creative Commons Attribution-Noncommercial-ShareAlike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1109/cdc51059.2022.9992904
