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Slowdown of growth controls cellular differentiation
Jatin Narula1, Anna Kuchina2, Fang Zhang2
1Department of Bioengineering, Rice University, Houston, TX, USA.
Molecular Systems Biology
|May 25, 2016
Summary
Cellular growth rate influences regulatory networks, impacting differentiation. Slowing growth in Bacillus subtilis increases sporulation regulator Spo0A activity, enabling starvation detection without direct stress signals.
Area of Science:
- Microbiology
- Systems Biology
- Cellular Differentiation
Background:
- Cellular differentiation processes are crucial for multicellular organisms.
- Regulatory networks govern cell fate decisions.
- Bacillus subtilis sporulation serves as a model for differentiation.
Purpose of the Study:
- To investigate how changes in cellular growth rate affect regulatory network behavior.
- To understand the impact of growth rate on cellular differentiation outcomes, specifically starvation response in Bacillus subtilis.
- To elucidate the mechanism by which cells sense starvation through growth rate modulation.
Main Methods:
- Mathematical modeling of the phosphorelay network controlling Spo0A activity.
- Experimental validation of model predictions.
- Analysis of phosphorelay protein concentration and activity under varying growth rates.
Main Results:
- Spo0A activity increases as cellular growth rate decreases.
- Phosphorelay protein accumulation and extended replication periods contribute to increased Spo0A activity during growth slowdown.
- A critical growth rate threshold determines entry into sporulation.
- Cellular growth rate sensing allows indirect detection of starvation.
Conclusions:
- Growth rate serves as an indirect indicator of starvation in Bacillus subtilis.
- The phosphorelay network integrates growth rate information to regulate sporulation.
- Sensing growth rates enables cells to optimize differentiation in response to nutrient availability.
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