Anti-windup strategies for biomolecular control systems facilitated by model reduction theory for sequestration networks.

Robust perfect adaptation, a system property whereby a variable adapts to persistent perturbations at steady state, has been recently realized in living cells using genetic integral controllers. In certain scenarios, such controllers may lead to "integral windup," an adverse condition caused by saturating control elements, which manifests as error accumulation, poor dynamic performance, or instabilities. To mitigate this effect, we here introduce several biomolecular anti-windup topologies and link them to control-theoretic anti-windup strategies.

Inteins: A Swiss army knife for synthetic biology.

Inteins are proteins found in nature that execute protein splicing. Among them, split inteins stand out for their versatility and adaptability, presenting creative solutions for addressing intricate challenges in various biological applications. Their exquisite attributes, including compactness, reliability, orthogonality, low toxicity, and irreversibility, make them of interest to various fields including synthetic biology, biotechnology and biomedicine.

A cybergenetic framework for engineering intein-mediated integral feedback control systems.

The ability of biological systems to tightly regulate targeted variables, despite external and internal disturbances, is known as Robust Perfect Adaptation (RPA). Achieved frequently through biomolecular integral feedback controllers at the cellular level, RPA has important implications for biotechnology and its various applications. In this study, we identify inteins as a versatile class of genetic components suitable for implementing these controllers and present a systematic approach for their design.

Biomolecular feedback controllers: from theory to applications.

Billions of years of evolution have led to the creation of sophisticated genetic regulatory mechanisms that control various biological processes in a timely and precise fashion, despite their uncertain and noisy environments. Understanding such naturally existing mechanisms and even designing novel ones will have direct implications in various fields such as biotechnology, medicine, and synthetic biology. In particular, many studies have revealed that feedback-based control mechanisms inside the living cells endow the overall system with multiple attractive features, including homeostasis, noise reduction, and high dynamic performance.

A genetic mammalian proportional-integral feedback control circuit for robust and precise gene regulation.

The processes that keep a cell alive are constantly challenged by unpredictable changes in its environment. Cells manage to counteract these changes by employing sophisticated regulatory strategies that maintain a steady internal milieu. Recently, the antithetic integral feedback motif has been demonstrated to be a minimal and universal biological regulatory strategy that can guarantee robust perfect adaptation for noisy gene regulatory networks in .

A hierarchy of biomolecular proportional-integral-derivative feedback controllers for robust perfect adaptation and dynamic performance.

Proportional-Integral-Derivative (PID) feedback controllers are the most widely used controllers in industry. Recently, the design of molecular PID-controllers has been identified as an important goal for synthetic biology and the field of cybergenetics. In this paper, we consider the realization of PID-controllers via biomolecular reactions.

Order reduction and efficient implementation of nonlinear nonlocal cochlear response models.

The cochlea is an indispensable preliminary processing stage in auditory perception that employs mechanical frequency-tuning and electrical transduction of incoming sound waves. Cochlear mechanical responses are shown to exhibit active nonlinear spatiotemporal response dynamics (e.g.