Biology subjects

Alexis, E.

Publications and source records attributed to Alexis, E..

3 recordsLinked to original sources

bioRxiv2022

Regulation strategies for two-output biomolecular networks

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 previous traditional concepts describing one-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 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.

synthetic biology↗

bioRxiv2021

Dichotomous Feedback: A Signal Sequestration-based Feedback Mechanism for Biocontroller Design

We introduce a new design framework for implementing negative feedback regulation in Synthetic Biology, which we term dichotomous feedback. Our approach is different from current methods, in that it sequesters existing fluxes in the process to be controlled, and in this way takes advantage of the processs architecture to design the control law. This signal sequestration mechanism appears in many natural biological systems and can potentially be easier to realise than molecular sequestration and other comparison motifs that are nowadays common in biomolecular feedback control design. The loop is closed by linking the strength of signal sequestration to the process output. Our feedback regulation mechanism is motivated by two-component signalling systems, where we introduce a second response regulator competing with the natural response regulator thus sequestering kinase activity. Here, dichotomous feedback is established by increasing the concentration of the second response regulator as the level of the output of the natural process increases. Extensive analysis demonstrates how this type of feedback shapes the signal response, attenuates intrinsic noise while increasing robustness and reducing crosstalk.

synthetic biology↗

bioRxiv2021

Biomolecular mechanisms for signal differentiation

Cells can sense temporal changes of molecular signals, allowing them to predict environmental vari-ations and modulate their behaviour. This paper elucidates the underlying biomolecular mechanisms of time derivative computation, facilitating the design of reliable synthetic differentiator devices for a variety of applications, ultimately expanding our understanding of cell behaviour. In particular, we describe and analyse three alternative biomolecular topologies that work as signal differentiators of high accuracy to arbitrary input signals around their nominal operation. We propose strategies to preserve their performance even in the presence of high-frequency input signal components, which are detrimental to the performance of most differentiators. We found that the core of the proposed topologies appears in natural regulatory networks and we further discuss their biological relevance. The simple structure of our designs makes them promising tools for realizing derivative control action in synthetic biology.

synthetic biology↗