Regulation strategies for two-output biomolecular networks

Author:

Alexis Emmanouil1ORCID,Schulte Carolin C. M.12ORCID,Cardelli Luca3ORCID,Papachristodoulou Antonis1ORCID

Affiliation:

1. Department of Engineering Science, University of Oxford, Oxford OX1 3PJ, UK

2. Department of Biology, University of Oxford, Oxford OX1 3RB, UK

3. Department of Computer Science, University of Oxford, Oxford OX1 3QD, UK

Abstract

Feedback control theory facilitates the development of self-regulating systems with desired performance which are predictable and insensitive to disturbances. Feedback regulatory topologies are found in many natural systems and have been of key importance in the design of reliable synthetic bio-devices operating in complex biological environments. Here, we study control schemes for biomolecular processes with two outputs of interest, expanding previously described concepts based on single-output systems. Regulation of such processes may unlock new design possibilities but can be challenging due to coupling interactions; also potential disturbances applied on one of the outputs may affect both. We therefore propose architectures for robustly manipulating the ratio/product and linear combinations of the outputs as well as each of the outputs independently. To demonstrate their characteristics, we apply these architectures to a simple process of two mutually activated biomolecular species. We also highlight the potential for experimental implementation by exploring synthetic realizations both in vivo and in vitro . This work presents an important step forward in building bio-devices capable of sophisticated functions.

Funder

Engineering and Physical Sciences Research Council

Keble College De Breyne Scholarship

Royal Society Research Professorship

Biotechnology and Biological Sciences Research Council

Clarendon Fund

Publisher

The Royal Society

Subject

Biomedical Engineering,Biochemistry,Biomaterials,Bioengineering,Biophysics,Biotechnology

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