Related Experiment Video
Updated: May 17, 2026
09:20
Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells
Published on: July 6, 2021
A design principle for a posttranslational biochemical oscillator.
Craig C Jolley1, Koji L Ode, Hiroki R Ueda
1Laboratory for Systems Biology, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
Cell Reports
|October 23, 2012
Summary
Biological oscillators can exhibit oscillations through multisite phosphorylation. This study reveals that a simple substrate with two modification sites and opposing enzymes can generate oscillations, with implications for circadian clock mechanisms.
Area of Science:
- Biochemistry
- Systems Biology
- Theoretical Biology
Background:
- Multisite phosphorylation is crucial for biological oscillators like the circadian clock.
- The general role of multisite phosphorylation in oscillations remains unclear.
Purpose of the Study:
- To investigate the fundamental mechanisms driving oscillations in biological systems.
- To explore the role of multisite phosphorylation in creating and regulating biological oscillators.
Main Methods:
- Developed a theoretical model of a simple substrate with two modification sites.
- Simulated the system with two opposing enzymes (kinase and phosphatase).
- Performed computational analysis to identify key oscillatory motifs.
Main Results:
- Identified a unidirectional modification cycle and enzyme sequestration as key characteristics of the oscillator.
- Demonstrated how these motifs create coupled systems for single-molecule oscillation and population synchronization.
- Showed conditions for temperature compensation of the oscillation period.
Conclusions:
- A simple theoretical model explains oscillation generation via multisite phosphorylation.
- Unidirectional cycles and enzyme sequestration are critical for robust biological oscillations.
- This framework aids in analyzing and designing posttranslational oscillators, including those in the circadian clock.
Related Concept Videos
02:19Circadian Rhythms and Gene Regulation
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
02:19Circadian Rhythms and Gene Regulation
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
01:45Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
02:39Positive Regulator Molecules
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
01:23Operon Model
The operon model represents a fundamental mechanism of gene regulation in prokaryotes, enabling coordinated expression of genes involved in related metabolic or functional pathways. Operons consist of structural genes, a promoter, and an operator, with transcription regulated by repressors, activators, and small effector molecules.Structure and Function of OperonsAn operon is a cluster of structural genes transcribed together under the control of a single promoter. The promoter region...
01:29Translational Regulation
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...