7 research outputs found

    TABASCO: A single molecule, base-pair resolved gene expression simulator-0

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    <p><b>Copyright information:</b></p><p>Taken from "TABASCO: A single molecule, base-pair resolved gene expression simulator"</p><p>http://www.biomedcentral.com/1471-2105/8/480</p><p>BMC Bioinformatics 2007;8():480-480.</p><p>Published online 19 Dec 2007</p><p>PMCID:PMC2242808.</p><p></p>SA, and using the Tabasco gene expression simulator (Figure 3). The Tabasco-based simulation uses a transcription initiation model (a) with the rest of gene expression using the general schematic shown in Figure 1. We constructed the model for the species-level simulator (b) to mimic the Tabasco-based model, except that elongation reactions were treated as single-lumped reactions

    TABASCO: A single molecule, base-pair resolved gene expression simulator-3

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    <p><b>Copyright information:</b></p><p>Taken from "TABASCO: A single molecule, base-pair resolved gene expression simulator"</p><p>http://www.biomedcentral.com/1471-2105/8/480</p><p>BMC Bioinformatics 2007;8():480-480.</p><p>Published online 19 Dec 2007</p><p>PMCID:PMC2242808.</p><p></p>s from tracking individual molecules (Single Molecule Resolution) to grouping them into species (Species Level Resolution). The arrows represent reactions that can occur (process labeled in blue)

    TABASCO: A single molecule, base-pair resolved gene expression simulator-2

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    <p><b>Copyright information:</b></p><p>Taken from "TABASCO: A single molecule, base-pair resolved gene expression simulator"</p><p>http://www.biomedcentral.com/1471-2105/8/480</p><p>BMC Bioinformatics 2007;8():480-480.</p><p>Published online 19 Dec 2007</p><p>PMCID:PMC2242808.</p><p></p> creation of implicit rules defined by the state of protein-DNA interactions and of the DNA itself. For example, when a traversing polymerase occupies a genetic element such as a protein-DNA binding site (a), the binding site is inactivated and prevented from binding a protein until the polymerase completely clears the site. Activation of genetic elements by entry of DNA into the cell (b) and inter-polymerase interactions (c) can be directly simulated as well. Finally, in complex genetic environments (d) where multiple promoters and terminators regulate the expression of genes, a priori transcription levels for each protein need not be calculated, for they are generated implicitly

    Refactored M13 Bacteriophage as a Platform for Tumor Cell Imaging and Drug Delivery

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    M13 bacteriophage is a well-characterized platform for peptide display. The utility of the M13 display platform is derived from the ability to encode phage protein fusions with display peptides at the genomic level. However, the genome of the phage is complicated by overlaps of key genetic elements. These overlaps directly couple the coding sequence of one gene to the coding or regulatory sequence of another, making it difficult to alter one gene without disrupting the other. Specifically, overlap of the end of gene VII and the beginning of gene IX has prevented the functional genomic modification of the N-terminus of p9. By redesigning the M13 genome to physically separate these overlapping genetic elements, a process known as “refactoring,” we enabled independent manipulation of gene VII and gene IX and the construction of the first N-terminal genomic modification of p9 for peptide display. We demonstrate the utility of this refactored genome by developing an M13 bacteriophage-based platform for targeted imaging of and drug delivery to prostate cancer cells <i>in vitro</i>. This successful use of refactoring principles to re-engineer a natural biological system strengthens the suggestion that natural genomes can be rationally designed for a number of applications

    One-Step Cloning and Chromosomal Integration of DNA

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    We describe “clonetegration”, a method for integrating DNA into prokaryotic chromosomes that approaches the simplicity of cloning DNA within extrachromosomal vectors. Compared to existing techniques, clonetegration drastically decreases the time and effort needed for integration of single or multiple DNA fragments. Additionally, clonetegration facilitates cloning and expression of genetic elements that are impossible to propagate within typical multicopy plasmids

    Artificial Symmetry-Breaking for Morphogenetic Engineering Bacterial Colonies

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    Morphogenetic engineering is an emerging field that explores the design and implementation of self-organized patterns, morphologies, and architectures in systems composed of multiple agents such as cells and swarm robots. Synthetic biology, on the other hand, aims to develop tools and formalisms that increase reproducibility, tractability, and efficiency in the engineering of biological systems. We seek to apply synthetic biology approaches to the engineering of morphologies in multicellular systems. Here, we describe the engineering of two mechanisms, symmetry-breaking and domain-specific cell regulation, as elementary functions for the prototyping of morphogenetic instructions in bacterial colonies. The former represents an artificial patterning mechanism based on plasmid segregation while the latter plays the role of artificial cell differentiation by spatial colocalization of ubiquitous and segregated components. This separation of patterning from actuation facilitates the design-build-test-improve engineering cycle. We created computational modules for CellModeller representing these basic functions and used it to guide the design process and explore the design space <i>in silico</i>. We applied these tools to encode spatially structured functions such as metabolic complementation, RNAPT7 gene expression, and CRISPRi/Cas9 regulation. Finally, as a proof of concept, we used CRISPRi/Cas technology to regulate cell growth by controlling methionine synthesis. These mechanisms start from single cells enabling the study of morphogenetic principles and the engineering of novel population scale structures from the bottom up

    SBOL: A community standard for communicating designs in synthetic biology

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    <p>Abstract</p> <p>The Synthetic Biology Open Language (SBOL) is a proposed data standard for exchanging designs within the synthetic biology community. SBOL represents synthetic biology designs in a community-adopted, formalized format for exchange between software tools, research groups, and commercial service providers. The re-use of previously validated designs is critical to the evolution of synthetic biology from a research discipline to an engineering practice. As a community-driven standard, SBOL adapts as synthetic biology evolves, providing specific capabilities for different aspects of the synthetic biology workflow. The SBOL Developers Group has implemented SBOL 1.1 as an XML/RDF serialization and provides software libraries and specification documentation to help developers implement SBOL in their own software. This paper also reports on early successes, including a demonstration of the utility of SBOL for information exchange between three different tools from three academic sites.</p> <p> </p
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