Computational Modeling of Planktonic and Biofilm Metabolism

dc.contributor.authorGuo, Weihuaen
dc.contributor.committeechairFeng, Xueyangen
dc.contributor.committeememberSenger, Ryan S.en
dc.contributor.committeememberZhang, Chenmingen
dc.contributor.committeememberHe, Zhenen
dc.contributor.departmentBiological Systems Engineeringen
dc.date.accessioned2017-10-17T08:00:30Zen
dc.date.available2017-10-17T08:00:30Zen
dc.date.issued2017-10-16en
dc.description.abstractMost of microorganisms are ubiquitously able to live in both planktonic and biofilm states, which can be applied to dissolve the energy and environmental issues (e.g., producing biofuels and purifying waste water), but can also lead to serious public health problems. To better harness microorganisms, plenty of studies have been implemented to investigate the metabolism of planktonic and/or biofilm cells via multi-omics approaches (e.g., transcriptomics and proteomics analysis). However, these approaches are limited to provide the direct description of intracellular metabolism (e.g., metabolic fluxes) of microorganisms. Therefore, in this study, I have applied computational modeling approaches (i.e., 13C assisted pathway and flux analysis, flux balance analysis, and machine learning) to both planktonic and biofilm cells for better understanding intracellular metabolisms and providing valuable biological insights. First, I have summarized recent advances in synergizing 13C assisted pathway and flux analysis and metabolic engineering. Second, I have applied 13C assisted pathway and flux analysis to investigate the intracellular metabolisms of planktonic and biofilm cells. Various biological insights have been elucidated, including the metabolic responses under mixed stresses in the planktonic states, the metabolic rewiring in homogenous and heterologous chemical biosynthesis, key pathways of biofilm cells for electricity generation, and mechanisms behind the electricity generation. Third, I have developed a novel platform (i.e., omFBA) to integrate multi-omics data with flux balance analysis for accurate prediction of biological insights (e.g., key flux ratios) of both planktonic and biofilm cells. Fourth, I have designed a computational tool (i.e., CRISTINES) for the advanced genome editing tool (i.e., CRISPR-dCas9 system) to facilitate the sequence designs of guide RNA for programmable control of metabolic fluxes. Lastly, I have also accomplished several outreaches in metabolic engineering. In summary, during my Ph.D. training, I have systematically applied computational modeling approaches to investigate the microbial metabolisms in both planktonic and biofilm states. The biological findings and computational tools can be utilized to guide the scientists and engineers to derive more productive microorganisms via metabolic engineering and synthetic biology. In the future, I will apply 13C assisted pathway analysis to investigate the metabolism of pathogenic biofilm cells for reducing their antibiotic resistance.en
dc.description.degreePh. D.en
dc.format.mediumETDen
dc.identifier.othervt_gsexam:13002en
dc.identifier.urihttp://hdl.handle.net/10919/79669en
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subject13C assisted pathway and flux analysisen
dc.subjectplanktonic and biofilm metabolismen
dc.subjectflux balance analysisen
dc.subjectmulti-omics analysisen
dc.subjectMachine learningen
dc.subjectCRISPR-Cas9en
dc.subjectmetabolic engineeringen
dc.subjectbiofuelsen
dc.subjectcell-free protein synthesisen
dc.titleComputational Modeling of Planktonic and Biofilm Metabolismen
dc.typeDissertationen
thesis.degree.disciplineBiological Systems Engineeringen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePh. D.en

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