Thermodynamics of synthetic biological circuits

The goal of this project will be to create a general theoretical framework to study the non-equilibrium thermodynamics of biological systems with particular focus on synthetic circuits in cell-free environments.

To do this, we will rely on the recently developed theory of stochastic thermodynamics, which makes it possible to study the fluctuating thermodynamics of small-scaled systems arbitrary far from equilibrium.Firstly, we will construct a framework to determine the thermodynamic performance of any given synthetic biological circuits.

This can be done by breaking the complicated circuits up into specific modules and derive general expressions for the thermodynamic properties of these individual modules.

We will first look at cell-free translation-free nucleic-acid networks, and subsequently extend the results to transcription-translation systems and cellular implementations.Secondly, this framework will be used to optimize the thermodynamic performance of some of the most important biologically relevant circuits.

We will first focus on simple network motives such as toggle-switches and oscillators, where we will study the optimal network structures leading to the correct behaviour.

Subsequently, we will move to more complicated systems such as molecular amplifiers and absolute concentration robust sensors, where we will look at optimal designs, but also derive general trade-off relations between dissipation and robustness.We expect that our results will lead to new design principles for synthetic circuits and give a better understanding of what can and cannot be done using these synthetic networks, but we also believe that our results will lead to a better understanding of the motives behind the evolution of real gene-regulatory networks.