Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

Enzyme sequestration as a tuning point in controlling response dynamics of signalling networks

Tools
- Tools
+ Tools

Feng, Song, Ollivier, Julien F. and Soyer, Orkun S. (2016) Enzyme sequestration as a tuning point in controlling response dynamics of signalling networks. PLoS Computational Biology, 12 (5). e1004918. doi:10.1371/journal.pcbi.1004918

[img]
Preview
PDF
WRAP_journal.pcbi.1004918.PDF - Published Version - Requires a PDF viewer.
Available under License Creative Commons Attribution 4.0.

Download (3560Kb) | Preview
Official URL: http://dx.doi.org/10.1371/journal.pcbi.1004918

Request Changes to record.

Abstract

Signalling networks result from combinatorial interactions among many enzymes and scaffolding proteins. These complex systems generate response dynamics that are often essential for correct decision-making in cells. Uncovering biochemical design principles that underpin such response dynamics is a prerequisite to understand evolved signalling networks and to design synthetic ones. Here, we use in silico evolution to explore the possible biochemical design space for signalling networks displaying ultrasensitive and adaptive response dynamics. By running evolutionary simulations mimicking different biochemical scenarios, we find that enzyme sequestration emerges as a key mechanism for enabling such dynamics. Inspired by these findings, and to test the role of sequestration, we design a generic, minimalist model of a signalling cycle, featuring two enzymes and a single scaffolding protein. We show that this simple system is capable of displaying both ultrasensitive and adaptive response dynamics. Furthermore, we find that tuning the concentration or kinetics of the sequestering protein can shift system dynamics between these two response types. These empirical results suggest that enzyme sequestration through scaffolding proteins is exploited by evolution to generate diverse response dynamics in signalling networks and could provide an engineering point in synthetic biology applications.

Item Type: Journal Article
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Cells -- Decision making -- Research, Enzyme kinetics, Biochemical engineering, Synthetic biology
Journal or Publication Title: PLoS Computational Biology
Publisher: Public Library of Science
ISSN: 1553-7358
Official Date: 10 May 2016
Dates:
DateEvent
10 May 2016Published
17 April 2016Accepted
18 October 2015Submitted
Volume: 12
Number: 5
Article Number: e1004918
DOI: 10.1371/journal.pcbi.1004918
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
Funder: Engineering and Physical Sciences Research Council (EPSRC), University of Warwick. School of Life Sciences
Grant number: EP/H04986X/1

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics

twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us