Can cells ensure constant average abundances without increasing variability around averages?

What is it about?

Synthetic biology seeks to engineer biological circuits for diverse applications in health, environment, and industry. A key challenge of this approach is to engineer modular gene regulatory circuits that are robust to perturbations. Previous experimental and theoretical work established remarkable control modules that guarantee constant average molecular abundances across different environments. However, these control modules increased variability around averages ('noise') as an unexpected side-effect of conferring robustness to average abundances. Based on theoretical and computational analyses we propose a biomolecular circuit design that achieves both perfect adaption of average abundances and effective noise suppression simultaneously. We also present theoretical evidence that previously studied circuit designs can achieve near-perfect adaptation and effective noise suppression simultaneously. The previously reported limit thus seems a singularity that applies only when considering the hypothetical case of perfect adaptation.

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Photo by CDC on Unsplash

Photo by CDC on Unsplash

Why is it important?

Our results revise fundamental limits on robust control of biological systems. These results have a practical application: they suggest a control module to confer robust adaptation for biomolecular abundances without a noise penalty, which may be advantageous in synthetic biology applications compared to previously implemented control modules.