11. ENTRAINMENT OF A TUNABLE GENETIC OSCILLATOR IN ESCHERICHIA COLI
Department: Bioengineering
Faculty Advisor(s):
Jeff Hasty
Primary Student
Name: Octavio Mondragon-Palomino
Email: omondrag@ucsd.edu
Phone: 858-534-5722
Grad Year: 2011
Student Collaborators
Tal Danino, tdanino@ucsd.edu
Abstract
We have previously built a genetic oscillator in Escherichia coli that is fast, robust and persistent. The oscillatory expression of its components results from the interaction between two feedback loops of opposite sign. The period of oscillations can be tuned through the concentration of transcription inducers, Arabinose and IPTG (isopropyl b-D-1-thiogalactopyranoside), in cell media. Each cell is an independent oscillator.
Although the phase of oscillations is partly inherited from mother to daughter cells, oscillators loose their initial synchrony after a few periods. A natural next step in the advancement of synthetic biological oscillations is to achieve their coordinated behavior.
The objective of this work is to study the entrainment of the oscillator by modulating the concentrations of Arabinose and/or IPTG in cell media over time. To this end, we have created a microfluidic platform that combines long term confinement of a population of a few hundred cells in a monolayer, with a dynamic switch for the generation of a chemical signal. In this way, our microfluidic platform allows us to obtain single cell data for long periods of time (days) and modulate the entraining signal in frequency and amplitude.
We are also working towards constructing oscillator strains that display narrow period distributions. The period of oscillation is subject to cell-to-cell variability, for example from the number of copies of each plasmid. As the distribution of periods in a population of oscillators is narrower, the entrainment at a single frequency should be stronger.
Highly coordinated and tunable oscillators could be useful in biotechnological applications, for example to drive a chemical reaction inside cells in a bioreactor.
Related Links:
All Content Copyright 2008 Regents of the University of California. All rights reserved.
Official Web page of the University of California, San Diego.
