Biology subjects

M. Zand, A.

Publications and source records attributed to M. Zand, A..

3 recordsLinked to original sources

bioRxiv2025

Control with Practical Guarantees of Stationary Variance in Stochastic Chemical Reaction Networks

Biomolecular integral feedback controllers offer precise regulation of molecular species copy numbers, making them valuable for synthetic biology applications. Antithetic integral feedback controllers, in particular, can be effective in low-copy-number regimes with stochastic dynamics. In this work, we introduce a modified variant of this controller, called the antithetic dual-rein integral feedback motif, and analyze its performance from a stochastic perspective in the presence of intrinsic dynamic randomness. We demonstrate that our controller enables first-moment control while maintaining a tractable steady-state variance bound under specific parametric regimes. Notably, this variance bound is tunable, as it depends solely on the controller parameters. We derive these results using stochastic model-order reduction and validate them through numerical simulations. Our findings provide new insights into achieving both precise regulation and noise suppression in stochastic genetic circuits.

synthetic biology↗

bioRxiv2024

Multi-Layer Autocatalytic Feedback Enables Integral Control Amidst Resource Competition and Across Scales

Integral feedback control strategies have proven effective in regulating protein expression in unpredictable cellular environments. These strategies, grounded in model-based designs and control theory, have advanced synthetic biology applications. Autocatalytic integral feed-back controllers, utilizing positive autoregulation for integral action, are particularly promising due to their similarity to natural behaviors like self-replication and positive feedback seen across biological scales. However, their effectiveness is often hindered by resource competition and context-dependent couplings. This study addresses these challenges with a multi-layer feedback strategy, enabling population-level integral feedback and multicellular integrators. We provide a generalized mathematical framework for modeling resource competition in complex genetic networks, supporting the design of intracellular control circuits. Our controller motif demonstrated precise regulation in tasks ranging from gene expression control to population growth in multi-strain communities. We also explore a variant capable of ratiometric control, proving its effectiveness in managing gene ratios and co-culture compositions in engineered microbial ecosystems. These findings offer a versatile approach to achieving robust adaptation and homeostasis from subcellular to multicellular scales.

synthetic biology↗

bioRxiv2024

Cascaded Antithetic Integral Feedback Motifs for Robust Stability and Performance Improvement

Precise intracellular regulation and robust perfect adaptation can be achieved using biomolecular integral controllers and it holds enormous potential for synthetic biology applications. In this letter, we consider the cascaded implementation of a class of such integrator motifs. Our cascaded integrators underpin proportional-integral-derivative (PID) control structures, which we leverage to suggest ways to improve dynamic performance. Moreover, we demonstrate how our cascaded strategy can be harnessed to enhance robust stability in a class of uncertain reaction networks. We also discuss the genetic implementation of our controllers and the natural occurrence of their cascaded sequestration pairs in bacterial pathogens.

synthetic biology↗