Optimum Threshold Minimizes Noise in Timing of Intracellular Events

Area of Science:

• Molecular and Cellular Biology
• Systems Biology
• Virology

Background:

• Cellular event timing is crucial for biological processes.
• Noisy gene expression can impact the timing of intracellular events.
• Bacteriophage lambda provides a model system to study lysis timing.

Purpose of the Study:

• To investigate how stochastic protein expression affects the timing of cell lysis.
• To understand the relationship between lysis time noise and duration.
• To identify mechanisms that regulate lysis timing precision.

Main Methods:

• Site-directed mutagenesis of the bacteriophage lambda holin gene to create variants with different lysis times.
• Single-cell observation of lysis times for these variants.
• Development of a mathematical model incorporating stochastic protein expression and cell growth dilution.

Main Results:

• Lysis times varied from 30 to 190 minutes among phage variants.
• A non-monotonic relationship was observed between lysis time noise and lysis duration: noise decreased to a minimum and then increased sharply.
• The mathematical model successfully explained the observed noise profile.

Conclusions:

• Stochastic holin expression and dilution due to cell growth are key factors determining lysis timing noise.
• Specific holin accumulation thresholds can lead to precise lysis timing.
• This study provides insights into how noise in gene expression influences the timing of critical cellular events.