On the Role of Delays in Biological Systems : Analysis and Design

This work quantifies the nature of delays in genetic regulatory networks and their effect on system dynamics. It is known that a time lag can emerge from a sequence of biochemical reactions. Applying this modeling framework to the protein production processes, delay distributions are derived in a stochastic (probability density function) and deterministic setting (impulse function), whilst being shown to be equivalent under different assumptions. The dependence of the distribution properties on rate constants, gene length, and time-varying temperatures is investigated. Overall, the distribution of the delay in the context of protein production processes is shown to be highly dependent on the size of the genes and mRNA strands as well as the reaction rates. Results suggest longer genes have delay distributions with a smaller relative variance, and hence, less uncertainty in the completion times, however, they lead to larger delays. On the other hand large uncertainties may actually play a positive role, as broader distributions can lead to larger stability regions when this formalization of the protein production delays is incorporated into a feedback system.

Furthermore, evidence suggests that delays may play a role as an explicit design into existing controlling mechanisms. Accordingly, the reccurring dual-feedback motif is also investigated with delays incorporated into the feedback channels. The dual-delayed feedback is shown to have stabilizing effects through a control theoretic approach. Lastly, a distributed delay based controller design method is proposed as a potential design tool. In a preliminary study, the dual-delayed feedback system re-emerges as an effective controller design.

CLADP - THE CAMBRIDGE LINEAR ANALYSIS AND DESIGN PROGRAMS USER REFERENCE MANUAL (4TH ISSUE: APRIL 1983).

CLADP is an engineering software program developed at Cambridge University for the interactive computer aided design of feedback control systems. CLADP contains a wide range of tools for the analysis of complex systems, and the assessment of their performance when feedback control is applied, thus enabling control systems to be designed to meet difficult performance objectives. The range of tools within CLADP include the latest techniques in the field whose central theme is the extension of classical frequency domain concepts (well known and well proven for single loop systems) to multivariable or multiloop systems, and by making extensive use of graphical presentation information is provided in a readily understood form.

CLADP: THE CAMBRIDGE LINEAR ANALYSIS AND DESIGN PROGRAMS.

An interactive software facility for designing multivariable control systems is described. The paper discusses the desirable characteristics of such a facility, the particular capabilities of CLADP and the numerical algorithms which lie behind them.