Analysis of primitive genetic interactions for the design of a genetic signal differentiator

Abstract

We study the dynamic and static input–output behavior of several primitive genetic interactions and their effect on the performance of a genetic signal differentiator. In a simplified design, several requirements for the linearity and time-scales of processes like transcription, translation and competitive promoter binding were introduced. By experimentally probing simple genetic constructs in a cell-free experimental environment and fitting semi-mechanistic models to these data, we show that some of these requirements can be verified, while others are only met with reservations in certain operational regimes. Analyzing the linearized model of the resulting genetic network, we conclude that it approximates a differentiator with relative degree one. Taking also the discovered nonlinearities into account and using a describing function approach, we further determine the particular frequency and amplitude ranges where the genetic differentiator can be expected to behave as such.

Biomolecular mechanisms for signal differentiation

“…Recent efforts in this rather underexplored research area include the design of a differentiator module consisting of linear input/output functions realized by specific processes of protein production [14, 15]. It has further been demonstrated that calculation of time derivatives is possible by using ultrasensitive topologies operating within a negative feedback loop [16], and a motif capable of computing positive and negative temporal gradients, which includes input delays and the idea of an incoherent feed-forward loop, has been presented [17].…”

AC-BioSD : A biomolecular signal differentiator module with enhanced performance (extended version)

“…BioSD modules can also be employed for derivative control, potentially in conjunction with proportional and integral action (PID control) [17]. Note that different approaches to realizing derivative action (including derivative control) via biochemical interactions have been proposed in the recent literature [12]- [16], [18], [20]- [22]. For a concise comparative discussion, we refer the reader to [23].…”

Biomolecular mechanisms for signal differentiation

“…Recent efforts in this rather underexplored research area include the design of a differentiator module consisting of linear input/output functions realized by specific processes of protein production ( Halter et al., 2017 ; Halter et al., 2019 ). It has further been demonstrated that calculation of time derivatives is possible by using ultrasensitive topologies operating within a negative feedback loop ( Samaniego et al., 2019 ), and a motif capable of computing positive and negative temporal gradients, which includes input delays and the idea of an incoherent feedforward loop, has been presented ( Samaniego et al., 2020 ).…”