Microfluidic devices for measuring gene network dynamics in single cells

Abstract

The dynamics governing gene regulation have an important role in determining the phenotype of a cell or organism. From processing extracellular signals to generating internal rhythms, gene networks are central to many time-dependent cellular processes. Recent technological advances now make it possible to track the dynamics of gene networks in single cells under various environmental conditions using microfluidic 'lab-on-a-chip' devices, and researchers are using these new techniques to analyse cellular dynamics and discover regulatory mechanisms. These technologies are expected to yield novel insights and allow the construction of mathematical models that more accurately describe the complex dynamics of gene regulation.The study of gene regulation has undergone a transformation over the past decade owing to the maturation of new technologies and an increased interest in the topic among mathematical biologists. New assay techniques, particularly those involving DNA microarrays or fluorescent proteins, have allowed researchers to quantify the relative levels of gene expression in cells and test mathematical models of gene networks in vivo. These technologies are at the heart of two new scientific disciplines, namely 'systems biology' and 'synthetic biology', each of which takes a starkly different approach to the study of gene regulation 1 . Systems biologists take a top-down approach by studying entire large-scale gene networks with the goal of obtaining an integrated understanding of genomic function [2][3][4] . By contrast, synthetic biologists take a bottom-up approach by studying simplified gene networks consisting of just one or a few genes with the goal of uncovering the fundamental principles and mechanisms that govern gene regulation. The definition of synthetic biology is now very broad and includes general work on metabolic and genetic engineering. Here, we use the term to refer to the original definition: the study of gene regulation through the creation of mathematical models and simple de novo circuits. Although we focus on synthetic biology in this Review, systems and synthetic NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript biology are connected by the belief that mathematical and computational modelling will lead to a better understanding of gene regulation 5 .Because synthetic biologists are more concerned with the intricacies of gene regulation, their models tend to include more details of molecular dynamics than those from systems biology. The ability to probe the dynamics of gene networks at the single-cell level is key to the synthetic biology approach. Systems-level effects that control whole genomes or even multicellular and population-scale phenomena are important, but synthetic biologists take the stance that an understanding of the mechanisms underlying gene regulation is just as important and will aid our overall understanding of phenotypic responses. To probe these small-scale interactions and mechanisms, some synthetic biology laboratories have begu...

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