Coupled positive and negative feedbacks produce diverse gene expression patterns in colonies

Area of Science:

• Microbiology
• Systems Biology
• Mathematical Biology

Background:

• Pattern formation is crucial in developing multicellular organisms and microbial communities.
• Gene expression patterns within colonies are not fully understood.
• Feedback mechanisms are common in cellular regulatory networks.

Purpose of the Study:

• To investigate the formation of gene expression patterns in microbial colonies using a mathematical model.
• To explore how a coupled positive-and-negative-feedback genetic circuit influences colony-wide patterns.
• To compare simulation results with experimental observations in Escherichia coli.

Main Methods:

• Development of a two-dimensional mathematical model for colony growth with a specific genetic circuit.
• Simulation of gene expression patterns under varying dynamics and nutrient diffusion.
• Reconstruction of the regulatory circuit in Escherichia coli.
• Experimental observation of gene expression patterns on colony surfaces.

Main Results:

• The model successfully generated diverse patterns, including sectored, target, uniform, and scattered gene expression.
• Experimental results in Escherichia coli showed patterns consistent with simulation predictions.
• Simple gene expression rules were sufficient to produce a range of complex colony patterns.
• Variations in cellular protein content were identified as a source of colony heterogeneity.

Conclusions:

• A simple genetic circuit with positive and negative feedback can generate diverse gene expression patterns in microbial colonies.
• Computational modeling and experimental validation provide a robust framework for studying colony development.
• Cellular heterogeneity, particularly in protein content, plays a significant role in shaping colony-level patterns.
• The findings have implications for understanding microbial community development and synthetic biology applications.