Space-induced bifurcation in repression-based transcriptional circuits

Area of Science:

• Systems Biology
• Synthetic Biology
• Computational Biology

Background:

• Molecular mechanisms of gene expression are known, but their dynamics are less understood.
• Spatial organization of molecular actors within cells is increasingly recognized.
• The impact of spatial localization on gene expression dynamics remains unclear, particularly in synthetic biology.

Purpose of the Study:

• To investigate the influence of spatial gene distribution on the dynamics of 3-gene transcriptional ring networks (repressilators).
• To determine if spatial parameters can alter gene expression dynamics in silico.
• To explore the potential of spatial control in synthetic gene circuits.

Main Methods:

• Individual-based modeling was employed to simulate gene expression dynamics.
• Simulations were conducted in both two and three spatial dimensions.
• Variations in gene demixing and molecular diffusion ranges were systematically analyzed.

Main Results:

• Spatial parameters, including gene demixing and molecular diffusion range, dramatically affected network dynamics.
• Transitions were observed between spontaneous oscillations and stationary states (constant fluctuations).
• These transitions were termed 'space-induced bifurcations'.

Conclusions:

• Spatial organization of molecular actors is critical for transcriptional network dynamics.
• Spatial localization of synthetic genes can be a novel control mechanism in synthetic biology.
• Findings suggest spatial arrangement can be leveraged to fine-tune synthetic gene circuit behavior.