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This study focused on the connection between the EnvZ/OmpR two-component regulatory system and the iron homeostasis system in Escherichia coli, specifically how a mutant form of EnvZ11/OmpR is able to reduce the expression of fepA::lacZ, a reporter gene fusion in E. coli. FepA is one of several outer membrane siderophore

This study focused on the connection between the EnvZ/OmpR two-component regulatory system and the iron homeostasis system in Escherichia coli, specifically how a mutant form of EnvZ11/OmpR is able to reduce the expression of fepA::lacZ, a reporter gene fusion in E. coli. FepA is one of several outer membrane siderophore receptors that allow extracellular siderophores bound to iron to enter the cells to power various biological processes. Previous studies have shown that in E. coli cells that expressed a mutant allele of envZ, called envZ11, which led to altered expression of various iron genes including down regulation of fepA::lacZ. The wild type EnvZ/OmpR system is not considered to regulate iron genes, but because these envz11 strains had downregulated fepA::lacZ, this study was undertaken to understand the connection and mechanisms of this downregulation. A large number of Lac+ revertants were obtained from the B32-2483 strain (envz11 and fepA::lacZ) and 7 Lac+ revertants that had reversion mutations not directly correcting the envZ11 allele were further characterized. With P1 phage transduction genetic mapping that involved moving a kanamycin resistance marker linked to fepA::lacZ, two Lac+ revertants were found to have their reversion mutations in the fepA promoter region, while the other five revertants had their mutations mapping outside the fepA region. These two revertants underwent DNA sequencing and found to carry two different single base pair mutations in two different locations of the fepA promoter region. Each one is in the Fur repressor binding region, but one also may have affected the Shine-Dalgarno region involved in translation initiation. All 7 reveratants underwent beta-galactosidase assays to measure fepA::lacZ expression. The two revertants that had mutations in the fepA promoter region had significantly increased fepA activity, with the revertant with the Shine-Dalgarno mutation having the most elevated fepA expression. The other 5 revertants that did not map in the fepA region had fepA expression elevated to the same level as that found in the wild type EnvZ/OmpR background. The data suggest that the negative effect of envZ11 can be overcome by multiple mechanisms, including directly correcting the envZ11 allele or changing the fepA promoter region.
ContributorsKalinkin, Victor Arkady (Co-author) / Misra, Rajeev (Co-author, Thesis director) / Mason, Hugh (Committee member) / Foy, Joseph (Committee member) / Biomedical Informatics Program (Contributor) / School of Life Sciences (Contributor) / W. P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
The Dorrance Center for Rare Childhood Disorders is a unique research division at TGen (The Translational Genomics Research Institute) that provides personalized care to children and young adults facing rare, undiagnosed diseases. TGen scientists believe that the answers to these enigmatic disorders can often be found in a person's genetic

The Dorrance Center for Rare Childhood Disorders is a unique research division at TGen (The Translational Genomics Research Institute) that provides personalized care to children and young adults facing rare, undiagnosed diseases. TGen scientists believe that the answers to these enigmatic disorders can often be found in a person's genetic code. They aim to solve these genetic mysteries using whole exome sequencing, a method that prioritizes the protein-coding portion of the genome in the search for disease-causing variants. Unfortunately, a communication gap sometimes exists between the TGen scientists and the patients they serve. I have seen, first hand, the kind of confusion that this study elicits in the families of its participants. Therefore, for my thesis, I decided to create a booklet that is meant to provide some clarity as to what exactly The Dorrance Center for Rare Childhood Disorders does to help diagnose children with rare disorders. The purpose of the booklet is to dispel any confusion regarding the study by providing a general review of genetics and an application of these lessons to the relevant sequencing technology as well as a discussion of the causes and effects of genetic mutations that often times are linked to rare childhood disorders.
ContributorsCambron, Julia Claire (Author) / LaBelle, Jeffrey (Thesis director) / Huentelman, Matt (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2015-05
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Description
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a devastating illness that causes the degeneration of both upper and lower motor neurons, leading to eventual muscle atrophy. ALS rapidly progresses into paralysis, with patients typically dying due to respiratory complications within three to five years from the

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a devastating illness that causes the degeneration of both upper and lower motor neurons, leading to eventual muscle atrophy. ALS rapidly progresses into paralysis, with patients typically dying due to respiratory complications within three to five years from the onset of their symptoms. Even after many years of research and drug trials, there is still no cure, and current therapies only succeed in increasing life-span by approximately three months. With such limited options available for patients, there is a pressing need to not only find a cure, but also make new treatments available in order to ameliorate disease symptoms. In a genome-wide association study previously conducted by the Translational Genomics Research Institute (TGen), several single-nucleotide polymorphisms (SNPs) upstream of a novel gene, FLJ10968, were found to significantly alter risk for ALS. This novel gene acquired the name FGGY after publication of the paper. FGGY exhibits altered levels of protein expression throughout ALS disease progression in human subjects, and detectable protein and mRNA expression changes in a mouse model of ALS. We performed co-immunoprecipitation experiments coupled with mass spectrometry in order to determine which proteins are associated with FGGY. Some of these potential binding partners have been linked to RNA regulation, including regulators of the splicesomal complex such as SMN, Gemin, and hnRNP C. To further validate these findings, we have verified co-localization of these proteins with one another. We hypothesize that FGGY plays an important role in ALS pathogenesis, and we will continue to examine its biological function.
ContributorsTerzic, Barbara (Author) / Jensen, Kendall (Thesis director) / Francisco, Wilson (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
The interaction between England and Scotland is complicated and continually changing. Scottish writer Sir Walter Scott examines this long-standing relationship through his various writings. Scott conveys a presence that is both acutely aware of the damages enacted upon Scotland by various English political efforts, and sensitive to the delicate relationshi

The interaction between England and Scotland is complicated and continually changing. Scottish writer Sir Walter Scott examines this long-standing relationship through his various writings. Scott conveys a presence that is both acutely aware of the damages enacted upon Scotland by various English political efforts, and sensitive to the delicate relationship that the two regions had begun to form during his lifetime. Through a critical analysis of Scott's novel, Rob Roy, one can see the various strategies Scott used to balance the need to address prior controversies within the relationship, and the petition to move beyond the prior conflict and develop a mutual understanding of each culture. Through this, Scott is able to regenerate a sense of Scottish nationalism for his people, and encourage improved relations within the British Isles.
ContributorsChotena, Chelsea (Author) / Facinelli, Diane (Thesis director) / Foy, Joseph (Committee member) / White, Julianne (Committee member) / Barrett, The Honors College (Contributor)
Created2013-05
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Description
The purpose of this thesis is to examine the current atmosphere of genetic patent law and use economic theory to construct models which describe the consequences of the legal code. I intend to analyze the four specific cases of Diamond v. Chakrabarty, Association for Molecular Pathology v. Myriad Genetics, the

The purpose of this thesis is to examine the current atmosphere of genetic patent law and use economic theory to construct models which describe the consequences of the legal code. I intend to analyze the four specific cases of Diamond v. Chakrabarty, Association for Molecular Pathology v. Myriad Genetics, the Alzheimer's Institute of America v. Jackson Laboratory, and the harm caused by PGx Health's monopoly over the LQTS gene.
ContributorsVolz, Caleb Richard (Author) / DeSerpa, Allan (Thesis director) / Silverman, Daniel (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Economics Program in CLAS (Contributor)
Created2014-05
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Description
Gle1 is an mRNP export mediator with major activity localized to the nuclear pore complex in eukaryotic cells. The protein's high preservation across vast phylogenetic distances allows us to approximate research on the properties of yeast Gle1 (yGle1) with those of human Gle1 (hGle1). Research at Vanderbilt University in 2016,

Gle1 is an mRNP export mediator with major activity localized to the nuclear pore complex in eukaryotic cells. The protein's high preservation across vast phylogenetic distances allows us to approximate research on the properties of yeast Gle1 (yGle1) with those of human Gle1 (hGle1). Research at Vanderbilt University in 2016, which provides the research basis of this thesis, suggests that the coiled-coil domain of yGle1 is best crystallized in dicationic aqueous conditions of pH ~8.0 and 10\u201420% PEG 8000. Further exploration of crystallizable microconditions revealed a favorability toward lower pH and lower PEG concentration. Following the discovery of the protein's native crystallography conditions, a comprehensive meta-analysis of scientific literature on Gle1 was conducted on the association of Gle1 mutations with neuron disease.
ContributorsGaetano, Philip Pasquale (Author) / Foy, Joseph (Thesis director) / Dawson, T. Renee (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12