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School of Biological Sciences

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https://hdl.handle.net/1853/70750

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Organizational Unit

College of Sciences

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Center for the Study of Systems Biology

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https://finding-aids.library.gatech.edu/agents/corporate_entities/1131

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Publication Search Results

Now showing 1 - 10 of 13

Computational tools for molecular epidemiology and computational genomics of Neisseria meningitidis

(Georgia Institute of Technology, 2010-11-17) Katz, Lee Scott

Neisseria meningitidis is a gram negative, and sometimes encapsulated, diplococcus that causes devastating disease worldwide. For the worldwide genetic surveillance of N. meningitidis, the gold standard for profiling the bacterium uses genetic loci found around the genome. Unfortunately, the software for analyzing the data for these profiles is difficult to use for a variety of reasons. This thesis shows my suite of tools called the Meningococcus Genome Informatics Platform for the analysis of these profiling data. To better understand N. meningitidis, the CDC Meningitis Laboratory and other world class laboratories have adopted a whole genome approach. To facilitate this approach, I have developed a computational genomics assembly and annotation pipeline called the CG-Pipeline. It assembles a genome, predicts locations of various features, and then annotates those features. Next, I developed a comparative genomics browser and database called NBase. Using CG-Pipeline and NBase, I addressed two open questions in N. meningitidis research. First, there are N. meningitidis isolates that cause disease but many that do not cause disease. What is the genomic basis of disease associated versus asymptomatically carried isolates of N. meningitidis? Second, some isolates' capsule type cannot be easily determined. Since isolates are grouped into one of many serogroups based on this capsule, which aids in epidemiological studies and public health response to N. meningitidis, often an isolate cannot be grouped. Thus the question is what is the genomic basis of nongroupability? This thesis addresses both of these questions on a whole genome level.
Controls on nitrogen fixation and nitrogen release in a diazotrophic endosymbiont of shipworms

(Georgia Institute of Technology, 2010-11-15) Horak, Rachel Elizabeth Ann

Nitrogen fixation is an ecologically important microbial process that can contribute bioavailable combined N to habitats low in N. Shipworms, or wood-boring bivalves, host N2-fixing and cellulolytic symbiotic bacteria in gill bacteriocytes, which have been implicated as a necessary adaptation to an N-poor C-rich (wooden) diet. Shipworm symbionts are known to fix N within the gill habitat and newly fixed N is subsequently incorporated into non-symbiont containing host tissue. The presence of N2-fixation in gill bacteriocytes presents a conundrum because N2-fixation is tightly regulated by oxygen in most other diazotrophic microbes. Also, the direct evidence of new N being incorporated into the host tissue indicates that there are potentially complex nutrient cycles in this symbiosis, which have not been investigated. We used the cultivated symbiont Teredinibacter turnerae, which has been isolated from many shipworm species, as a model organism to elucidate controls on N2-fixation and N release in the shipworm symbiosis. Our results indicate that headspace oxygen concentration does not control biomass specific N2-fixation and respiration activity in T. turnerae, but it does influence the magnitude of the growth rate and timing of culture growth. Also, we examined the controls of oxygen on inorganic nutrient uptake rates, and documented a small amount of dissolved inorganic nitrogen release. While the N budget is only partially balanced, we provide indirect evidence for the allocation of fixed N to the excretion of exopolymeric substances and dissolved organic nitrogen; future studies that measure these additional N sinks are necessary to close the N budget. Although there are limitations of using pure cultures to investigate a complex symbiotic system, this study provides direct experimental evidence that T. turnerae has adaptations that are conducive to N2-fixation in gill bacteriocytes.
A novel mode of bacterial respiration: iron solubilization prior to electron transfer

(Georgia Institute of Technology, 2010-11-11) Fennessey, Christine Michelle

Microbial iron respiration contributes significantly to the biogeochemical cycling of metals and may be one of the earliest respiratory processes to have evolved on early earth. Metal-respiring microbes also hold great potential for use in microbial fuel cells for the generation of "green" energy and for remediation of radionuclides in contaminated environments. Despite its significance in global metal cycling processes, the molecular mechanism of Fe(III) respiration has yet to be determined. Unlike many other terminal electron acceptors, Fe(III) is a solid at circumneutral pH and, therefore, cannot come into direct contact with the microbial inner membrane: the site of terminal electron transfer in gram-negative bacteria. It is postulated that metal-respiring organisms have developed alternate strategies for the reduction of solid iron. One such strategy involves the production of an Fe(III)-solublizing ligand by the metal-respiring bacteria which solubilizes the Fe(III) prior to respiration, rendering the metal more easily accessible to the Fe(III) reductase complex. In this study, the genes involved in the solubilization of Fe(III) by the gram-negative dissimilatory metal reducing bacteria Shewanella oneidensis MR-1 were determined using random mutagenesis to generate mutations in the wild-type genome and high-throughput square-wave voltammetry to screen for the attenuation of Fe(III) production in the mutants. Two mutants unable to solubilize Fe(III) were identified and designated d29 and d64. After mutation complementation analysis, it was determined that the point mutations were both located in type II secretion genes: gspG and gspE respectively, indicating that the type II secretion system is required for Fe(III) solubilization prior to respiration. It was also hypothesized that the ligand produced for Fe(III) solubilization during dissimilatory Fe(III) respiration was a siderophore: a small Fe(III)-chelating molecule produced by the cells for the assimilation of Fe(III) for growth. A siderophore biosynthesis gene (SO3031) and a siderophore ferric reductase gene (SO3034) were deleted in frame and the resultant mutants screened to determine whether they were capable of Fe(III) solubilization and reduction during anaerobic Fe(III) respiration. Both mutants retained Fe(III) solubilization and reduction activity, indicating that the siderophore Fe(III) assimilatory system is distinct from the Fe(III) solubilization system utilized during Fe(III) respiration. The work presented here is significant in that it describes a rapid screening method for identifying Fe(III) solubilization mutants, reports on the involvement of the type II secretion system in Fe(III) solubilization during iron respiration, and finally demonstrates that a dissimilatory metal reducing bacteria synthesizes and secretes Fe(III)-chelating molecules which are distinct from Fe(III)-siderophores.
Robustness and hierarchical control of performance variables through coordination during human locomotion

(Georgia Institute of Technology, 2010-11-03) Auyang, Arick Gin-Yu

The kinematic motor redundancy of the human legs provides more local degrees of freedom than are necessary to achieve low degree of freedom performance variables like leg length and orientation. The purpose of this dissertation is to investigate how the neuromuscular skeletal system simplifies control of a kinematically redundant system to achieve stable locomotion under different conditions. I propose that the neuromuscular skeletal system minimizes step to step variance of leg length and orientation while allowing segment angles to vary within the set of acceptable combinations of angles that achieves the desired leg length and orientation. I find that during human hopping, control of the locomotor system is organized hierarchically such that leg length and orientation are achieved by structuring segment angle variance. I also found that leg length and leg orientation was minimized for a variety of conditions and perturbations, including frequency, constrained foot placement, and different speeds. The results of this study will give valuable information on interjoint compensation strategies used when the locomotor system is perturbed. This work also provides evidence for neuromuscular system strategies in adapting to novel, difficult tasks. This information can be extended to give insight into new and different areas to focus on during gait rehabilitation of humans suffering from motor control deficits in movement and gait.
Algorithm development for next generation sequencing-based metagenome analysis

(Georgia Institute of Technology, 2010-08-26) Kislyuk, Andrey O.

We present research on the design, development and application of algorithms for DNA sequence analysis, with a focus on environmental DNA (metagenomes). We present an overview and primer on algorithm development for bioinformatics of metagenomes; work on frameshift detection in DNA sequencing data; work on a computational pipeline for the assembly, feature prediction, annotation and analysis of bacterial genomes; work on unsupervised phylogenetic clustering of metagenomic fragments using Markov Chain Monte Carlo methods; and work on estimation of bacterial genome plasticity and diversity, potential improvements to the measures of core and pan-genomes.
The evolution of cleaning mutualism and predator cooperation in a radiation of Caribbean fishes

(Georgia Institute of Technology, 2010-07-07) Lettieri, Liliana B.

The steps by which neutral, random and/or negative biological interactions evolve into mutualistic ones remain poorly understood. Here, we study Elacatinus gobies and the fishes from which they clean parasites, termed 'clients'. Colorful stripes are common to mutualist cleaners and non-cleaning sister species. Blue stripes are unique to obligate cleaners. We quantified the contrast potential of ancestral and novel stripe colors, using fish color vision models, and determined that color stripes have become more visible to clients over evolutionary time. In turn, we focused on the role of color as a potentially specialized signal. We show that cleaners possess a putative chemical defense (one multimedia file in .mov format included) and demonstrate that stripes are sufficient to elicit client stereotypical posing behavior and to deter attack. Analysis of previously published records show that yellow cleaners tend to predators less than expected, compared to green and blue cleaners. Our results highlight evolution from predator avoidance to tolerance with conspicuous advertising reinforced by chemical defense in cleaners. Similar trajectories, via recognizable signals to risky partners, may be common in other diffuse mutualisms. We discuss the generality of defense and signal traits in other species rich lineages of mutualists.
Epigenetic regulation of the human genome by transposable elements

(Georgia Institute of Technology, 2010-07-07) Huda, Ahsan

Nearly one half of the human genome is composed of transposable elements (TEs). Once dismissed as 'selfish' or 'junk' DNA, TEs have also been implicated in a numerous functions that serve the needs of their host genome. I have evaluated the role of TEs in mediating the epigenetic mechanisms that serve to regulate human gene expression. These findings can be broadly divided into two major mechanisms by which TEs affect human gene expression; by modulating nucleosome binding in the promoter regions and by recruiting epigenetic histone modifications that enable them to serve as promoters and enhancers. Thus. the studies encompassed in this thesis elucidate the contributions of TEs in epigenetically regulating human gene expression on a global as well as local scale.
Aquatic plant-herbivore interactions across multiple spatial scales.

(Georgia Institute of Technology, 2010-05-21) Morrison, Wendy Elizabeth

For decades scientists believed that herbivory had minimal impact on freshwater ecosystems. We now know that herbivory in freshwater systems equals or exceeds herbivory in terrestrial and marine systems. In extreme cases, herbivores can change clear, macrophyte dominated ecosystems into turbid plankton dominated ecosystems. Even though research on plant-herbivore interactions in freshwater systems has increased, there is still much that is unknown. This thesis is comprised of four studies investigating freshwater plant-herbivore interactions across multiple spatial scales. The first study investigated how induced chemical defenses in Cabomba caroliniana suppress herbivore consumption and growth as well as how this herbivore-generated change in plant chemistry affects the growth of plant associated microbes. At the spatial scale of individual ponds or lakes, consumers that induce their host plants may also be indirectly affecting other consumers and microbial pathogens via changes in this shared resource. The second study moves to an ecosystem scale and investigates how exotic versus native apple snails may impact Everglades' habitats. We investigated plant preference, consumption, growth and conversion efficiencies in the singly native apple snail to occur in the U.S. (Pomacea paludosa) versus four introduced species (P. canaliculata, P. insularum, P. haustrum and P. diffusa). We found that even though plant preferences are similar, invasive snails tend to eat more, grow more rapidly, and sometimes more efficiently than natives. This suggests that invasive species could have a large impact on the environment, especially the abundance of submerged plants. The third study investigated how palatability of freshwater plants varies with latitude (i.e. geographic scale). Increased herbivory at lower latitudes is hypothesized to select for increased plant defenses, which has been shown to be true for tropical forests, salt marshes, and seaweeds. When we contrasted eight confamilial plants collected in Indiana versus Southern Florida, three of four herbivores significantly preferred northern plants. When we evaluated a second set of plants collected from Indiana versus Central Florida, only one of three herbivores preferred the northern plants. Overall, our results suggest a preference for northern plants, but the strength of this relationship was variable. We hypothesize that this variability may be driven by 1) local variance in herbivore pressure that creates variance in plant defenses, and/or 2) the effect of winter length on the survival and feeding rate of herbivores. The final study expanded to a world scale, and investigated herbivore preference for native vs exotic plants. We found that both N. American crayfish and S. American snails preferred exotic plants over confamilial natives, despite responding to different plant characteristics. The single species of apple snail that occurs in N. American showed no preference for native or exotic plants from a N. American perspective, but instead exhibited preferences that correlated with its history of evolution in S. America. As the N. American species is a sister species of the S. American snails, feeding by the N. American snail appears more affected by its S. American lineage than its recent history in N. America. This suggests that phylogenetic legacy will affect choices of the herbivore as well as resistance or susceptibility of plants.
Application of bioinformatics in studies of sphingolipid biosynthesis

(Georgia Institute of Technology, 2010-05-17) Momin, Amin Altaf

The studies in this dissertation demonstrate that the gene expression pathway maps are useful tools to notice alteration in different branches of sphingolipid biosynthesis pathway based on microarray and other transcriptomic analysis. To facilitate the integrative analysis of gene expression and sphingolipid amounts, updated pathway maps were prepared using an open access visualization tool, Pathvisio v1.1. The datasets were formatted using Perl scripts and visualized with the aid of color coded pathway diagrams. Comparative analysis of transcriptomics and sphingolipid alterations from experimental studies and published literature revealed 72.8 % correlation between mRNA and sphingolipid differences (p-value < 0.0001 by the Fisher's exact test).The high correlation between gene expression differences and sphingolipid alterations highlights the application of this tool to evaluate molecular changes associate with sphingolipid alterations as well as predict differences in specific metabolites that can be experimentally verified using sensitive approaches such as mass spectrometry. In addition, bioinformatics sequence analysis was used to identify transcripts for sphingolipid biosynthesis enzyme 3-ketosphinganine reductase, and homology modeling studies helped in the evaluation of a cell line defective in sphingolipid metabolism due to mutation in the enzyme serine palmitoyltransferase, the first enzyme of de novo biosynthesis pathway. Hence, the combination of different bioinformatics approaches, including protein and DNA sequence analysis, structure modeling and pathway diagrams can provide valuable inputs for biochemical and molecular studies of sphingolipid metabolism.
Genes encoding the key enzymes for the bacterial degradation of the natural nitro compounds 3-nitrotyrosine and 1-nitro-2-phenylethane.

(Georgia Institute of Technology, 2010-04-06) Parks, Samantha Terris

Natural nitro compounds with diverse structures and biological functions are produced by bacteria, fungi, plants and animals. Little is known about the behavior of such compounds in natural ecosystems. The lack of accumulation in the biosphere implies that they are biodegraded. Microbial strategies for biodegradation of synthetic nitro compounds are well established; however only two pathways are known for degradation of natural nitro compounds. The research described here examines the genes that encode the key enzymes required for biodegradation of 3-nitrotyrosine (3NTyr) and 1-nitro-2-phenylethane (NPE). 3NTyr is a biological marker for disease and inflammation in plants and animals. A 3NTyr degrading microbe, Variovorax sp. JS669 was isolated from soil. We identified the JS669 denA, which encodes an enzyme that catalyzes denitration of 4-hydroxy-3-nitro-phenylacetate, the key step in metabolism of 3NTyr. The isolation of 3NTyr degraders and development of molecular probes specific to denA revealed that 3NTyr degradation is a widespread phenomena in natural habitats and the compound is metabolized by phylogenetically diverse bacteria. Phylogenetic analysis of the 4-hydroxy-3-nitro-phenylacetate denitrase from JS669 revealed it to be the first functionally annotated protein in a clade of unidentified Class A flavin monooxygenases. NPE has been identified from several plants, yet the biodegradation of the compound remained a mystery. Here we report the degradation of NPE and its analog 2-nitropropylbenzene. Discovery of the metabolic pathway revealed a novel microbial strategy to use a meta-ring fission degradation pathway to cleave an undesirable side chain from an aromatic compound and use the remainder of the compound as a carbon and energy source. Two genes that encode enzymes in the biodegradation pathway were identified and both are deeply branched within their respective phylogenetic trees, indicating that both represent highly specialized microbial enzymes. Furthermore, microbial degradation of NPE resulted in the production of 3-nitropropionic acid, a natural toxin that inhibits succinate dehydrogenase and is responsible for livestock illness and death. This is the first report of bacterial production of 3-nitropropionic acid, and might represent a significant source of 3-nitropropionic acid in natural habitats. The findings from these studies contribute to the overall understanding of microbial metabolism. Specifically, this research reveals genes that encode novel enzymes and strategies for the biodegradation of two natural nitro compounds. Furthermore, discovery of mechanisms for the biodegradation of such compounds reveals novel microbial metabolic diversity and provides insight into the evolution of degradation pathways for synthetic compounds.