Digital microfluidics (DMF) is a liquid handling technique that has been demonstrated to automate biological experimentation in a low-cost, rapid, and programmable manner. This review discusses the role of DMF as a "digital bioconverter"-a tool to connect the digital aspects of the design-build-learn cycle with the physical execution of experiments. Several applications are reviewed to demonstrate the utility of DMF as a digital bioconverter, namely, genetic engineering, sample preparation for sequencing and mass spectrometry, and enzyme-, immuno-, and cell-based screening assays.
View Article and Find Full Text PDFComputational systems biology involves integrating heterogeneous datasets in order to generate models. These models can assist with understanding and prediction of biological phenomena. Generating datasets and integrating them into models involves a wide range of scientific expertise.
View Article and Find Full Text PDFBioModels serves as a central repository of mathematical models representing biological processes. It offers a platform to make mathematical models easily shareable across the systems modelling community, thereby supporting model reuse. To facilitate hosting a broader range of model formats derived from diverse modelling approaches and tools, a new infrastructure for BioModels has been developed that is available at http://www.
View Article and Find Full Text PDFThe ability to map environmental signals onto distinct internal physiological states or programmes is critical for single-celled microbes. A crucial systems dynamics feature underpinning such ability is multistability. While unlimited multistability is known to arise from multi-site phosphorylation seen in the signalling networks of eukaryotic cells, a similarly universal mechanism has not been identified in microbial signalling systems.
View Article and Find Full Text PDFSynthetic biology aims to design de novo biological systems and reengineer existing ones. These efforts have mostly focused on transcriptional circuits, with reengineering of signaling circuits hampered by limited understanding of their systems dynamics and experimental challenges. Bacterial two-component signaling systems offer a rich diversity of sensory systems that are built around a core phosphotransfer reaction between histidine kinases and their output response regulator proteins, and thus are a good target for reengineering through synthetic biology.
View Article and Find Full Text PDFAchieving a complete understanding of cellular signal transduction requires deciphering the relation between structural and biochemical features of a signaling system and the shape of the signal-response relationship it embeds. Using explicit analytical expressions and numerical simulations, we present here this relation for four-layered phosphorelays, which are signaling systems that are ubiquitous in prokaryotes and also found in lower eukaryotes and plants. We derive an analytical expression that relates the shape of the signal-response relationship in a relay to the kinetic rates of forward, reverse phosphorylation and hydrolysis reactions.
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