Biological significance of autoregulation through steady state analysis of genetic networks

Biological significance of autoregulation through steady state analysis of genetic network

Multiple feedback loop design in the tryptophan regulatory network of Escherichia coli suggests a paradigm for robust regulation of processes in series

Biological networks have evolved through adaptation in uncertain environments. Of the different possible design paradigms, some may offer functional advantages over others. These designs can be quantified by the structure of the network resulting from molecular interactions and the parameter values. One may, therefore, like to identify the design motif present in the evolved network that makes it preferable over other alternatives. In this work, we focus on the regulatory networks characterized by serially arranged processes, which are regulated by multiple feedback loops. Specifically, we consider the tryptophan system present in Escherichia coli, which may be conceptualized as three processes in series, namely transcription, translation and tryptophan synthesis. The multiple feedback loop motif results from three distinct negative feedback loops, namely genetic repression, mRNA attenuation and enzyme inhibition. A framework is introduced to identify the key design components of this network responsible for its physiological performance. We demonstrate that the multiple feedback loop motif, as seen in the tryptophan system, enables robust performance to variations in system parameters while maintaining a rapid response to achieve homeostasis. Superior performance, if arising from a design principle, is intrinsic and, therefore, inherent to any similarly designed system, either natural or engineered. An experimental engineering implementation of the multiple feedback loop design on a two-tank system supports the generality of the robust attributes offered by the design

GPCR mediated control of calcium dynamics: A systems perspective

G-protein coupled receptor (GPCR) mediated calcium (Ca2+)-signaling transduction remains crucial in designing drugs for various complex diseases including neurodegeneration, chronic heart failure as well as respiratory diseases. Although there are several reviews detailing various aspects of Ca2+-signaling such as the role of IP3 receptors and Ca2+-induced-Ca2+-release, none of them provide an integrated view of the mathematical descriptions of GPCR signal transduction and investigations on dose-response curves. This article is the first study in reviewing the network structures underlying GPCR signal transduction that control downstream [Cac2+]-oscillations. The central theme of this paper is to present the biochemical pathways, as well as molecular mechanisms underlying the GPCR-mediated Ca2+-dynamics in order to facilitate a better understanding of how agonist concentration is encoded in Ca2+-signals for Gαq, Gαs, and Gαi/o signaling pathways. Moreover, we present the GPCR targeting drugs that are relevant for treating cardiac, respiratory, and neuro-diseases. The current paper presents the ODE formulation for various models along with the detailed schematics of signaling networks. To provide a systems perspective, we present the network motifs that can provide readers an insight into the complex and intriguing science of agonist-mediated Ca2+-dynamics. One of the features of this review is to pinpoint the interplay between positive and negative feedback loops that are involved in controlling intracellular [Cac2+]-oscillations. Furthermore, we review several examples of dose-response curves obtained from [Cac2+]-spiking for various GPCR pathways. This paper is expected to be useful for pharmacologists and computational biologists for designing clinical applications of GPCR targeting drugs through modulation of Ca2+-dynamics

The production of fuels and chemicals from food processing wastes using a novel fermenter separator

During 1991, considerable progress was made on the waste utilization project. Two small Wisconsin companies have expressed an interest in promoting and developing the ICRS technology. Pilot plant sites at (1) Hopkinton, IA, for a sweet whey plant, and Beaver Dam WI, for an acid whey site have been under development siting ICRS operations. The Hopkinton, IA site is owned and operated by Permeate Refining Inc., who have built a batch ethanol plant across the street from Swiss Valley Farms cheddar cheese operations. Permeate from Swiss Valley is piped across to PRI. PRI has signed a contract to site a 300--500,000 gallon/yr to ICRS pilot plant. They feel that the lower labor, lower energy, continuous process offered by the ICRS will substantially improve their profitability. Catalytics, Inc, is involved with converting whey from a Kraft cream cheese operation to ethanol and yeast. A complete project including whey concentration, sterilization, and yeast growth has been designed for this site. Process design improvements with the ICRS focussed on ethanol recovery techniques during this year's project. A solvent absorption/extractive distillation (SAED) process has been developed which offers the capability of obtaining an anhydrous ethanol product from vapors off 3 to 9% ethanol solutions using very little energy for distillation. Work on products from waste streams was also performed. a. Diacetyl as a high value flavor compound was very successfully produced in a Stirred Tank Reactor w/Separation. b. Yeast production from secondary carbohydrates in the whey, lactic acid, and glycerol was studied. c. Lactic acid production from cellulose and lactose studies continued. d. Production of anti-fungal reagents by immobilized plant cells; Gossypol has antifungal properties and is produced by G. arboretum