Collective oscillation period of inter-coupled biological negative cyclic feedback oscillators

A number of biological rhythms originate from networks comprised of multiple cellular oscillators. But analytical results are still lacking on the collective oscillation period of inter-coupled gene regulatory oscillators, which, as has been reported, may be different from that of an autonomous oscillator. Based on cyclic feedback oscillators, we analyze the collective oscillation pattern of coupled cellular oscillators. First we give a condition under which the oscillator network exhibits oscillatory and synchronized behavior. Then we estimate the collective oscillation period based on a novel multivariable harmonic balance technique. Analytical results are derived in terms of biochemical parameters, thus giving insight into the basic mechanism of biological oscillation and providing guidance in synthetic biology design.Comment: arXiv admin note: substantial text overlap with arXiv:1203.125

Estados sincronizados en la dinámica de circuitos genéticos oscilatorios.

Los circuitos genéticos oscilatorios son un componente fundamental de la biología de los seres vivos. Estos circuitos están presentes en la fisiología de los todos los seres vivos a través de los circuitos circadianos y en muchos otros procesos de regulación, formación de patrones, etc (ver por ejemplo: Towards a physical understanding of developmental patterning, J. Negrete Jr, A. C. Oates, Nature Reviews Genetics 2021). El objetivo principal de este trabajo es analizar circuitos genéticos que presentan comportamientos oscilatorios basados en el retardo de las respuestas y los mecanismos de sincronización entre células aplicado a un modelo del reloj de segmentación en el proceso de somitogénesis. El estudio la dinámica del sistema ha revelado que los osciladores celulares experimentan una bifurcación de Hopf mediada por el retardo y que, al introducir el acoplo mediado por un segundo retardo intercelular, se observan ventanas de sincronización global o asincronía en función del valor que toma dicho retardo.<br /

Understanding Control of Metabolite Dynamics and Heterogeneity

Microbes live in complex and continually changing environments. Rapid shifts in nutrient availability are a common challenge for microbes, and cause changes in intracellular metabolite levels. Microbial response to dynamic environments requires coordination of multiple levels of cellular machinery including gene expression and metabolite concentrations. This coordination is achieved through metabolic control systems, which sense metabolite concentrations and direct cellular activity in response. Several reoccurring control architectures are found throughout diverse metabolic systems, which suggests underlying evolutionary advantages for using these control systems to coordinate metabolism. One common, yet understudied, control architecture is the positive feedback metabolite uptake loop, which features a metabolite responsive-transcription factor (MRTF) that activates genes necessary to uptake its cognate metabolite. Understanding the design principles behind these complex metabolic control systems is a fundamental issue across many biological sub-disciplines since metabolism is a central feature of cellular behavior.The goal of this dissertation is to elucidate how the architecture and parameters of a MRTF-based control system shape metabolite dynamics and heterogenous metabolic response to changing nutrient environments. This dissertation focuses on the Escherichia coli fatty acid degradation system, which employs the positive feedback uptake loop architecture. The function and performance of these control systems to three common metabolic tasks was evaluated. First, after a nutrient depletion, microbes must rapidly turn off metabolic pathways to conserve resources. Second, microbes must maintain sensing ability in the face of metabolic conditions which impact cellular growth rate. Finally, upon abrupt shifts between nutrients, microbes must shift metabolic resources to uptake the new nutrient or otherwise cease growth. This shifting process can be heterogenous, with a sub-population which maintains a non-growing state that confers tolerance to antimicrobial compounds. Taken together, this work provides deeper understanding of the design principles for the control of metabolite dynamics and heterogeneity for applications in metabolic engineering and synthetic biology