Telomeres prevent the ends of eukaryotic chromosomes from being recognized as damaged DNA and protect against cancer and ageing. When telomere structure is perturbed, a co-ordinated series of events ...promote arrest of the cell cycle so that cells carrying damaged telomeres do not divide. In order to better understand the eukaryotic response to telomere damage, budding yeast strains harboring a temperature sensitive allele of an essential telomere capping gene (cdc13-1) were subjected to a transcriptomic study.
The genome-wide response to uncapped telomeres in yeast cdc13-1 strains, which have telomere capping defects at temperatures above approximately 27 degrees C, was determined. Telomere uncapping in cdc13-1 strains is associated with the differential expression of over 600 transcripts. Transcripts affecting responses to DNA damage and diverse environmental stresses were statistically over-represented. BNA2, required for the biosynthesis of NAD+, is highly and significantly up-regulated upon telomere uncapping in cdc13-1 strains. We find that deletion of BNA2 and NPT1, which is also involved in NAD+ synthesis, suppresses the temperature sensitivity of cdc13-1 strains, indicating that NAD+ metabolism may be linked to telomere end protection.
Our data support the hypothesis that the response to telomere uncapping is related to, but distinct from, the response to non-telomeric double-strand breaks. The induction of environmental stress responses may be a conserved feature of the eukaryotic response to telomere damage. BNA2, which is involved in NAD+ synthesis, plays previously unidentified roles in the cellular response to telomere uncapping.
Synthetic biology builds upon the techniques and successes of genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. The field ...still faces substantial challenges, including long development times, high rates of failure, and poor reproducibility. One method to ameliorate these problems would be to improve the exchange of information about designed systems between laboratories. The Synthetic Biology Open Language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, filling a need not satisfied by other pre-existing standards. This document details version 2.1 of SBOL that builds upon version 2.0 published in last year’s JIB special issue. In particular, SBOL 2.1 includes improved rules for what constitutes a valid SBOL document, new role fields to simplify the expression of sequence features and how components are used in context, and new best practices descriptions to improve the exchange of basic sequence topology information and the description of genetic design provenance, as well as miscellaneous other minor improvements.
BacillOndex is an extension of the Ondex data integration system, providing a semantically annotated, integrated knowledge base for the model Gram-positive bacterium Bacillus subtilis. This ...application allows a user to mine a variety of B. subtilis data sources, and analyse the resulting integrated dataset, which contains data about genes, gene products and their interactions. The data can be analysed either manually, by browsing using Ondex, or computationally via a Web services interface. We describe the process of creating a BacillOndex instance, and describe the use of the system for the analysis of single nucleotide polymorphisms in B. subtilis Marburg. The Marburg strain is the progenitor of the widely-used laboratory strain B. subtilis 168. We identified 27 SNPs with predictable phenotypic effects, including genetic traits for known phenotypes. We conclude that BacillOndex is a valuable tool for the systems-level investigation of, and hypothesis generation about, this important biotechnology workhorse. Such understanding contributes to our ability to construct synthetic genetic circuits in this organism.
Synthetic biology builds upon the techniques and successes of genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. The field ...still faces substantial challenges, including long development times, high rates of failure, and poor reproducibility. One method to ameliorate these problems would be to improve the exchange of information about designed systems between laboratories. The Synthetic Biology Open Language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, filling a need not satisfied by other pre-existing standards. This document details version 2.0 of SBOL, introducing a standardized format for the electronic exchange of information on the structural and functional aspects of biological designs. The standard has been designed to support the explicit and unambiguous description of biological designs by means of a well defined data model. The standard also includes rules and best practices on how to use this data model and populate it with relevant design details. The publication of this specification is intended to make these capabilities more widely accessible to potential developers and users in the synthetic biology community and beyond.
As genetic circuits become more sophisticated, the size and complexity of data about their designs increase. The data captured goes beyond genetic sequences alone; information about circuit ...modularity and functional details improves comprehension, performance analysis, and design automation techniques. However, new data types expose new challenges around the accessibility, visualization, and usability of design data (and metadata). Here, we present a method to transform circuit designs into networks and showcase its potential to enhance the utility of design data. Since networks are dynamic structures, initial graphs can be interactively shaped into subnetworks of relevant information based on requirements such as the hierarchy of biological parts or interactions between entities. A significant advantage of a network approach is the ability to scale abstraction, providing an automatic sliding level of detail that further tailors the visualization to a given situation. Additionally, several visual changes can be applied, such as coloring or clustering nodes based on types (e.g., genes or promoters), resulting in easier comprehension from a user perspective. This approach allows circuit designs to be coupled to other networks, such as metabolic pathways or implementation protocols captured in graph-like formats. We advocate using networks to structure, access, and improve synthetic biology information.
GENETTA is a software tool that transforms synthetic biology designs into networks using graph theory for analysis and manipulation. By representing complex data as interconnected points, GENETTA ...allows dynamic customization of visualizations, including interaction networks and parts hierarchies. It can also merge design data from multiple databases, providing a unified perspective. The generated interactive network can be edited by adding nodes and edges, simplifying changes to existing design files. This article presents GENETTA and its features through specific use cases, showcasing its practical applications.
Summary
Sulfur‐oxidizing Sulfurimonas spp. are widespread in sediments, hydrothermal vent fields, aquifers and subsurface environments such as oil reservoirs where they play an important role in the ...sulfur cycle. We determined the genome sequence of the oil field isolate Sulfurimonas sp. strain CVO and compared its gene expression during nitrate‐dependent sulfide oxidation to the coastal sediment isolate Sulfurimonas denitrificans. Formation of elemental sulfur (S0) and high expression of sulfide quinone oxidoreductase (SQR) genes indicates that sulfide oxidation in both strains is mediated by SQR. Subsequent oxidation of S0 was achieved by the sulfur oxidation enzyme complex (SOX). In the coastal S. denitrificans, the genes are arranged and expressed as two clusters: soxXY1Z1AB and soxCDY2Z2H, and sulfate was the sole metabolic end product. By contrast, the oil field strain CVO has only the soxCDY2Z2H cluster and not soxXY1Z1AB. Despite the absence of the soxXY1Z1AB cluster, strain CVO oxidized S0 to thiosulfate and sulfate, demonstrating that soxCDY2Z2H genes alone are sufficient for S0 oxidation in Sulfurimonas spp. and that thiosulfate is an additional metabolic end product. Screening of publicly available metagenomes revealed that Sulfurimonas spp. with only the soxCDY2Z2H cluster are widespread suggesting this mechanism of thiosulfate formation is environmentally significant.
The SynBioHub repository (https://synbiohub.org) is an open-source software project that facilitates the sharing of information about engineered biological systems. SynBioHub provides computational ...access for software and data integration, and a graphical user interface that enables users to search for and share designs in a Web browser. By connecting to relevant repositories (e.g., the iGEM repository, JBEI ICE, and other instances of SynBioHub), the software allows users to browse, upload, and download data in various standard formats, regardless of their location or representation. SynBioHub also provides a central reference point for other resources to link to, delivering design information in a standardized format using the Synthetic Biology Open Language (SBOL). The adoption and use of SynBioHub, a community-driven effort, has the potential to overcome the reproducibility challenge across laboratories by helping to address the current lack of information about published designs.
PDF
