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Full-Text Articles in Systems Biology

Computational Analysis Of Transcriptional And Post-Transcriptional Feedback Loops In Development And Cell Differentiation, Benjamin Rigel Nordick Aug 2022

Computational Analysis Of Transcriptional And Post-Transcriptional Feedback Loops In Development And Cell Differentiation, Benjamin Rigel Nordick

Masters Theses

Regulation of gene expression is critical to organism development and health. Positive and negative feedback in networks of gene regulatory interactions are associated with the maintenance of distinct cell states/types or oscillations, respectively. Recent computational studies identified two structures of positive feedback relevant to establishment of cell type: interconnected transcriptional “high-feedback” loops and a purely post-transcriptional feedback loop arising from multiple microRNA molecules cooperatively regulating one mRNA. The goals of this work were to develop methods for analyzing often-unintuitive high-feedback loops in large networks, generalize the two new regulatory structures to consider oscillation, and further explore the ability of post-transcriptional …


Multi-Omic Systems Biological Analysis Of Host-Microbe Interactions, Piet Jones May 2022

Multi-Omic Systems Biological Analysis Of Host-Microbe Interactions, Piet Jones

Doctoral Dissertations

Systems biology offers the opportunity to understand the complex mechanisms of various biological phenomena. The wealth of data that is produced, at an increasing rate, provides the potential to meet this opportunity. Here we take an applied approach to integrate multiple omic level data sources in order to generate biologically relevant hypotheses. We apply a novel analysis pipeline to model both, in concert, the microbial and transcriptomic signature from COVID-19 positive patients. We show patients may suffer from an increased microbial burden, with an increased pathogen potential. Gene expression evidence further shows patients may exhibit a compromised barrier immunity, owing …


Bioinformatic And Experimental Approaches For Deeper Metaproteomic Characterization Of Complex Environmental Samples, Ramsunder Mahadevan Iyer Dec 2017

Bioinformatic And Experimental Approaches For Deeper Metaproteomic Characterization Of Complex Environmental Samples, Ramsunder Mahadevan Iyer

Doctoral Dissertations

The coupling of high performance multi-dimensional liquid chromatography and tandem mass spectrometry for characterization of microbial proteins from complex environmental samples has paved the way for a new era in scientific discovery. The field of metaproteomics, which is the study of protein suite of all the organisms in a biological system, has taken a tremendous leap with the introduction of high-throughput proteomics. However, with corresponding increase in sample complexity, novel challenges have been raised with respect to efficient peptide separation via chromatography and bioinformatic analysis of the resulting high throughput data. In this dissertation, various aspects of metaproteomic characterization, including …


In Silico Driven Metabolic Engineering Towards Enhancing Biofuel And Biochemical Production, Richard Adam Thompson May 2016

In Silico Driven Metabolic Engineering Towards Enhancing Biofuel And Biochemical Production, Richard Adam Thompson

Doctoral Dissertations

The development of a secure and sustainable energy economy is likely to require the production of fuels and commodity chemicals in a renewable manner. There has been renewed interest in biological commodity chemical production recently, in particular focusing on non-edible feedstocks. The fields of metabolic engineering and synthetic biology have arisen in the past 20 years to address the challenge of chemical production from biological feedstocks. Metabolic modeling is a powerful tool for studying the metabolism of an organism and predicting the effects of metabolic engineering strategies. Various techniques have been developed for modeling cellular metabolism, with the underlying principle …


Characterizing Early-Life Microbiome Functionality In Premature Infant Gut By A Metaproteomics Approach, Weili Xiong May 2016

Characterizing Early-Life Microbiome Functionality In Premature Infant Gut By A Metaproteomics Approach, Weili Xiong

Doctoral Dissertations

Microbes inhabit all parts of human body that are exposed to the environment and their interactions with human host mutually benefit each other and play significant roles in human health and diseases. The human gastrointestinal tract harbors the largest population of the microbiota and has gained broad research attention and efforts over the past decade. Colonization of the gut by microbes begins at birth and this early-life bacterial establishment can impact infants’ health and even the human health and lifestyle across an entire life span. Recent studies on community structure and composition of infant gut microbiota have revealed the species …


Computational Identification Of Terpene Synthase Genes And Their Evolutionary Analysis, Qidong Jia May 2016

Computational Identification Of Terpene Synthase Genes And Their Evolutionary Analysis, Qidong Jia

Doctoral Dissertations

Terpenoids, the largest and most structurally and functionally diverse class of natural compounds on earth, are mostly synthesized by plants to be involved in various plant environment interactions. Some terpenoids are classified as primary metabolites essential for plant growth and development. Terpene synthases (TPSs), the key enzymes for terpenoid biosynthesis, are the major determinant of the tremendous diversity of terpenoid carbon skeletons. The TPS genes represent a mid-size family of about 30-100 functional genes in almost all major sequenced plant genomes. TPSs are also found in fungi and bacteria, but microbial TPS genes share low levels of sequence similarity and …


Comparative Genomics Of Microbial Chemoreceptor Sequence, Structure, And Function, Aaron Daniel Fleetwood Dec 2014

Comparative Genomics Of Microbial Chemoreceptor Sequence, Structure, And Function, Aaron Daniel Fleetwood

Doctoral Dissertations

Microbial chemotaxis receptors (chemoreceptors) are complex proteins that sense the external environment and signal for flagella-mediated motility, serving as the GPS of the cell. In order to sense a myriad of physicochemical signals and adapt to diverse environmental niches, sensory regions of chemoreceptors are frenetically duplicated, mutated, or lost. Conversely, the chemoreceptor signaling region is a highly conserved protein domain. Extreme conservation of this domain is necessary because it determines very specific helical secondary, tertiary, and quaternary structures of the protein while simultaneously choreographing a network of interactions with the adaptor protein CheW and the histidine kinase CheA. This dichotomous …


Development Of An Experimental And Computational Platform For Enhanced Characterization Of Modified Peptides And Proteins In Environmental Proteomics, Ritin Sharma Aug 2014

Development Of An Experimental And Computational Platform For Enhanced Characterization Of Modified Peptides And Proteins In Environmental Proteomics, Ritin Sharma

Doctoral Dissertations

Over the last decade, mass spectrometry based proteomics has been established as the front-runner in systems-level protein expression studies. However, with the field progressing into research of more and more complex samples, novel challenges have been raised with respect to efficient protein extraction and computational matching. In this dissertation, various aspects in the proteomics workflow, including experimental and computational approaches, have been developed, optimized and systematically evaluated. In this work, some of the critical factors with respect to proteomics sample preparation, like available biomass, detergent removal methods, and intact protein fractionation to achieve deeper proteome measurements were evaluated. The presented …


Development And Application Of Mass Spectrometry-Based Proteomics To Generate And Navigate The Proteomes Of The Genus Populus, Paul Edward Abraham May 2013

Development And Application Of Mass Spectrometry-Based Proteomics To Generate And Navigate The Proteomes Of The Genus Populus, Paul Edward Abraham

Doctoral Dissertations

Historically, there has been tremendous synergy between biology and analytical technology, such that one drives the development of the other. Over the past two decades, their interrelatedness has catalyzed entirely new experimental approaches and unlocked new types of biological questions, as exemplified by the advancements of the field of mass spectrometry (MS)-based proteomics. MS-based proteomics, which provides a more complete measurement of all the proteins in a cell, has revolutionized a variety of scientific fields, ranging from characterizing proteins expressed by a microorganism to tracking cancer-related biomarkers. Though MS technology has advanced significantly, the analysis of complicated proteomes, such as …