Research Fellows Theses
Recent Submissions
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Propst, Matthew Stephen (September 10, 2008)[more][less]
Abstract: Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system (CNS) affecting 1 in 2000 of the US population. Susceptibility to MS is influenced by environmental, gender, genetic and pathogenic factors. For instance, there is a higher incidence of MS in women than men (2:1) and that there is a sudden onset of the disease between the ages of 15 and 50, suggesting that gender, age and puberty alter the susceptibility to the disease. The etiology of MS is not known, and although viral infection is suspected to be an initiating event. Theiler’s murine encephalomyelitis virus (TMEV) infection in SJL mice causes a biphasic disease in which the chronic phase causes an inflammatory demyelinating disease of the CNS which closely resembles MS. In the current study we utilize TMEV to investigate the influence of both age and gender on disease progression in this viral model of human multiple sclerosis. Here, we tested the hypothesis that age and gender significantly affect the pathogenesis of Theiler’s virus-induced disease in which we showed that males displayed worse symptoms than females at later ages of inoculation. URI: http://handle.tamu.edu/1969.1/85755 Files in this item: 1
MSPropst-ResearchFellowsThesis.pdf (388.7Kb) -
Muff, Rebecca A. (August 30, 2008)[more][less]
Abstract: Russia’s women have had a difficult time finding a voice in literature until as recently as the 1980s. With this new voice, many women writers have countered the widespread gender assumptions inherent in patriarchal Russian culture. This essay explores how four contemporary Russian women authors— Ludmilla Petrushevskaya, Nina Sadur, Tatyana Tolstaya, and Ludmila Ulitskaya—challenge binary gender stereotypes, particularly those concerning women. Each author has uniquely rejected a prescribed definition of ‘woman’ in her prose, and together the four authors form a literary rebellion against stereotypical notions of femininity. URI: http://handle.tamu.edu/1969.1/85752 Files in this item: 1
THESIS.pdf (604.1Kb) -
Tilford, Sarah (August 24, 2008)[more][less]
Abstract: During pregnancy in the mouse, extensive communication takes place between the conceptus (embryo/fetus and associated extraembryonic membranes) and uterus. Our focus centers on the uterine response to the conceptus. In ruminants, the conceptus produces interferon tau that induces interferon stimulated genes (ISGs) which likely regulate uterine receptivity, conceptus implantation, and conceptus growth and development. Our hypothesis is that ISGs are similarly induced in uterus during pregnancy in the mouse. If ISGs have a critical role in pregnancy establishment and maintenance in mammals, it is important to identify these ISGs in order to address fertility issues in human medicine. In this research, in situ hybridization analysis of uteri during gestation in the mouse was conducted to understand cell specific expression of selected ISGs during pregnancy. Of the fifteen ISGs investigated, ten (Irf1, Irf2, Irf6, Irf7, Isg15, Oas2, Plscr1, Stat1, Rsad2, Tlr4) were found to be expressed in the uterus during pregnancy. URI: http://handle.tamu.edu/1969.1/85750 Files in this item: 1
Tilford_thesis.pdf (1.242Mb) -
Chateau, Morgan (August 24, 2008)[more][less]
Abstract: Chromosomal DNA in our cells is wrapped around a histone protein octomer like thread on a spool, forming a structure called a nucleosome. Series of nucleosomes form the nuclear chromosomes found in all eukaryotic organisms. Modifications to histone proteins can change how accessible chromosomal DNA is to protein complexes that act on DNA. DNA sequences that are inaccessible are called silent chromatin and regions that can’t be transcribed are subject to “gene silencing.” Proper gene silencing is necessary for normal cell development and regulation. Incorrect or missing histone modifications can cause the loss of gene silencing and uncontrolled gene expression similar to the situation in cells of patients with cancer or leukemia. My project focuses on a histone modifying complex COMPASS. COMPASS is composed of eight proteins, one of which is the histone H3 methyltransferase Set1. There are seven Set1 homologs in yeast and over 60 Set1-like proteins in humans, including MLL, which is known to be associated with human leukemia. Previous studies have shown that Set1 and most COMPASS proteins are essential for gene silencing at the ribosomal DNA locus (rDNA) in yeast. The SET domain is the active site of the Set1 histone methyltransferase, where methyl groups are covalently attached to the fourth lysine residue (K4) of histone H3. My goal is to investigate the effect of six individual amino acid substitutions in the SET domain of Set1; Y967A, I972A, Y993A, H1017L, Y967F, and G951A, on histone H3 methylation and gene silencing. These altered Set1 proteins are being expressed in the yeast Saccharomyces cerevisiae. Using Western blots and marker genes, the effect of these mutations are compared to wild type Set1. My data show that there are defects in histone H3 methylation in the amino acid substitution variants of Set1. In five of the mutants there is a complete loss of H3K4 methylation. In the future, we will determine if these altered Set1 proteins are assembled into the COMPASS complex. By characterizing the catalytic domain of Set1 using amino acid substitution variants, we will acquire a better understanding of the related proteins in humans. URI: http://handle.tamu.edu/1969.1/85749 Files in this item: 1
Thesis 2008 Final n.pdf (621.3Kb) -
Owen, Joshua (August 3, 2008)[more][less]
Abstract: The emergence of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb) has intensified efforts to discover novel drugs for tuberculosis (TB) treatment. Targeting the persistent state of Mtb, a condition in which Mtb is resistant to conventional drug therapies, is of particular interest. Persistent bacteria rely on metabolic pathways that are distinct from active infection Mtb as the environmental conditions of the persistent state are different (e.g., low nutrient). Because persistent Mtb are forced to survive in a low nutrient environment, a short, two enzyme pathway that becomes heavily utilized and upregulated is the glyoxylate shunt. Since the glyoxylate shunt enzymes are not present in mammals, they make attractive drug targets. We are studying malate synthase (MS), one of the enzymes in the glyoxylate shunt. We used computational, biochemical, and cellular techniques to identify potential inhibitors of MS. Crystal structures of MS in complex with inhibitors were used to rationally design better MS inhibitors. MS inhibitors validated via an enzyme activity assay, were then tested against whole cells using a non-pathogenic form of mycobacteria, Mycobacterium smegmatis. In this manner, inhibitors against MS have been identified and characterized for further development into potential novel antitubercular drugs. URI: http://handle.tamu.edu/1969.1/85728 Files in this item: 1
Senior_thesis-J_Owen.pdf (2.988Mb)
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