Enzyme promiscuity shapes adaptation to novel growth substrates
Not Available
59 BASIC BIOLOGICAL SCIENCES↗
Engineering topics
King, Zachary A.
Publications and source records attributed to King, Zachary A..
Optimization of Energy Flow Through Synthetic Metabolic Modules and Regulatory Networks in a Model Photosynthetic Eukaryotic Microbe
Diatoms are important oceanic photosynthetic microorganisms, responsible for approximately 20% of all carbon fixation on Earth. Additionally, diatoms are attractive metabolic engineering candidates. This investigation leveraged Systems Biology techniques to advance our understanding of and potential to engineer diatoms for bioproducts of societal interest, such as biofuels. Systems Biology combines computational and experimental techniques to understand an organism at the whole-cell level as well as characterize the interface between the organism and its environment. Our research resulted in major contributions to the understanding of systems-level light-driven metabolism. Diatoms have a unique evolutionary history. As a result, existing understanding of photosynthetic metabolism may not be applicable to diatom physiology. We generated, validated, and published a high-quality metabolic model of diatom metabolism facilitating novel insights into these unique organisms. Additionally, we overcame a consistent challenge in the modeling of photosynthetic organisms by integrating light into metabolic models. This result allows realistic assessments of how the light environment affects cell physiology and metabolism, a necessary advancement for bioengineering. Next, we generated several methodologies for integrating large-scale datasets with models of metabolism. These “big data” approaches begin to address a constant challenge in biology, which is translating data into information and understanding. Finally, we built web-based databases for housing, distributing, and visualizing systems-level biology data. These projects created an online ecosystem for sharing, analyzing, and characterizing metabolic information and is currently being used by public and private institutions. Photosynthetic bioengineering has the promise to create high-energy products with minimal inputs. Systems Biology has a long history of facilitating bioengineering of cellular metabolism. However, photosynthetic organisms are only sparsely present in this history. This project and its outputs have accelerated the application of proven Systems Biology techniques to light-driven metabolism. The resulting methodologies will accelerate public and private endeavors leveraging photosynthetic systems in the bioengineering of bioproducts such as biofuels or carbon sequestration.
09 BIOMASS FUELS↗
COBRAme: A computational framework for genome-scale models of metabolism and gene expression
Not Available
59 BASIC BIOLOGICAL SCIENCES↗
A Phaeodactylum tricornutum literature database for interactive annotation of content
Not Available
Gallina, Alessandra A.↗
BiGG Models: A platform for integrating, standardizing and sharing genome-scale models
In this study, genome-scale metabolic models are mathematically structured knowledge bases that can be used to predict metabolic pathway usage and growth phenotypes. Furthermore, they can generate and test hypotheses when integrated with experimental data. To maximize the value of these models, centralized repositories of high-quality models must be established, models must adhere to established standards and model components must be linked to relevant databases. Tools for model visualization further enhance their utility. To meet these needs, we present BiGG Models (http://bigg.ucsd.edu), a completely redesigned Biochemical, Genetic and Genomic knowledge base. BiGG Models contains more than 75 high-quality, manually-curated genome-scale metabolic models. On the website, users can browse, search and visualize models. BiGG Models connects genome-scale models to genome annotations and external databases. Reaction and metabolite identifiers have been standardized across models to conform to community standards and enable rapid comparison across models. Furthermore, BiGG Models provides a comprehensive application programming interface for accessing BiGG Models with modeling and analysis tools. As a resource for highly curated, standardized and accessible models of metabolism, BiGG Models will facilitate diverse systems biology studies and support knowledge-based analysis of diverse experimental data.
59 BASIC BIOLOGICAL SCIENCES↗
Escher: A Web Application for Building, Sharing, and Embedding Data-Rich Visualizations of Biological Pathways
Escher is a web application for visualizing data on biological pathways. Three key features make Escher a uniquely effective tool for pathway visualization. First, users can rapidly design new pathway maps. Escher provides pathway suggestions based on user data and genome-scale models, so users can draw pathways in a semi-automated way. Second, users can visualize data related to genes or proteins on the associated reactions and pathways, using rules that define which enzymes catalyze each reaction. Thus, users can identify trends in common genomic data types (e.g. RNA-Seq, proteomics, ChIP)—in conjunction with metabolite- and reaction-oriented data types (e.g. metabolomics, fluxomics). Third, Escher harnesses the strengths of web technologies (SVG, D3, developer tools) so that visualizations can be rapidly adapted, extended, shared, and embedded. This paper provides examples of each of these features and explains how the development approach used for Escher can be used to guide the development of future visualization tools.
59 BASIC BIOLOGICAL SCIENCES↗