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  • Thesis

  • Authors: Fleckenstein, Anne E. (2006)

  • Multiple drug resistance is quickly becoming an obstacle to the treatment of disease. Bacteria, parasitic protazoa, yeast and mammalian cancer cells develop mutations that render them resistant to a wide variety of structurally and chemically different compounds. In the yeast Saccharomyces cerevisiae, one of the main mechanisms causing drug resistance is the loss of function of ABC transporters that are responsible for effluxing the drug from the cell. The main ABC transporter responsible for efflux of many different drugs is Pdr5p. However, earlier work (Fleckenstein 1999; Shallom and Golin, 1996) shows that this is not the only pathway mediating resistance to these drugs. The global regulator Sin4p and the transcription factor YRRI operate in a PDR5-independent pathway to ...

  • Thesis

  • Authors: Walker, Megon Jarmaine (2006)

  • Understanding molecular interactions is at the core of computational biology and includes problems such as characterizing protein-protein, protein-small molecule, protein-DNA, and Protein-RNA binding events. These interactions are often elucidated by expensive and time-consuming assays during which candidate binders are screened against a target. The main aim of this dissertation is to improve the speed, cost, and overall efficiency of screening assays in the context of drug design and molecular systems biology. Sequential screening is an iterative process of experimentation and model refinement. Target binding activity is determined for samples of putative binders, results are used to update a classification model, and subsequent binding experiments are performed based on knowledg...

  • Thesis

  • Authors: O'Lone, Raegan Brie (2006)

  • Estrogen receptors (ERs) are cell-specific mediators of physiological changes. They act primarily as transcriptional regulators through binding DNA at specific target sequences, such as estrogen response elements (EREs), within gene regulatory regions. Few primary target genes of ERs have been identified, especially in nonreproductive tissues such as the vasculature, where estrogen responses impact both sexes. I initially utilized a bioinformatics approach to characterize known ER-regulated promoters, both with regards to primary estrogen response elements and to secondary transcription factor binding sites that may coregulate estrogen responses. Secondary promoter elements were identified as being overrepresented in promoters containing palindromic EREs The involvement of these pre...

  • Thesis

  • Authors: Vinar, Tomas (2006)

  • In this thesis, we present enhancements of hidden Markov models for the problem of finding genes in DNA sequences. Genes are the parts of DNA that serve as a template for synthesis of proteins. Thus. gene finding is a crucial step in the analysis of DNA sequencing data. Hidden Markov models are a key tool used in gene finding. Yhis thesis presents three methods for extending the capabilities of hidden Markov models to better capture the statistical properties of DNA sequences. In all three, we encounter limiting factors that lead to trade-offs between the model accuracy and those limiting factors. First. we build better models for recognizing biological signals in DNA sequences. Our new models capture non-adjacent dependencies within these signals. In this case. the main limiting ...

  • Thesis

  • Authors: Brejova, Bronislava (2006)

  • This thesis introduces new techniques for finding genes in genomic sequences. Genes are regions of a genome encoding proteins of an organism. Identification of genes in a genome is an important step in the annotation process after a new genome is sequenced. The prediction accuracy of gene finding can be greatly improved by using experimental evidence. This evidence includes homologies between the genome and databases of known proteins, or evolutionary conservation of genomic sequence in different species. We propose a flexible framework to incorporate several different sources of such evidence into a gene finder based on a hidden Markov model. Various sources of evidence are expressed as partial probabilistic statements about the annotation of positions in the sequence, and these a...

  • Thesis

  • Authors: Swingley, Wesley Douglas (2006)

  • Since the advent of life on this planet, photosynthetic prokaryotes have evolved to fill a variety of ecological niches. Many organisms have made novel adaptations in light harvesting mechanisms, pigment compositions, and opportunistic metabolic pathways. We set out to study two such organisms, Acaryochloris marina and Roseobacter denitrificans. The marine cyanobacterium A. marina lives in an environment where much of the photosynthetically active light is absorbed by another cyanobacterial species. Consequently, A. marina utilizes the unique pigment chlorophyll (Chi) d to absorb light that is unused by Chl a and b in the competing species. In spite of the lower-energy light absorbed by Chl d (-30 nm red-shifted) A. marina is able to perform the high-energy demanding oxygen evoluti...

  • Thesis

  • Authors: Kandil, Mahrous Mahmoud (2006)

  • Cyanuric acid is a key intermediate in the biodegradation pathway of atrazine which has been detected in ground and surface waters because of its widespread use around the world. Few strains are known for their ability to degrade and mineralize atrazine. Some of these strains harbor the atzD and trzD genes, which encode for cyanuric acid amidohydrolase, essential for cyanuric acid mineralization into carbon dioxide and ammonia. For more than 20 years, research has revealed that urea is one of the intermediates in cyanuric acid degradation. However, recent studies suggest that urea is not produced during the metabolism of atrazine or cyanuric acid. In this thesis, hundreds of isolates capable of degrading cyanuric acid were isolated and purified using direct plating method and a cle...

  • Article

  • Authors: Allen, Jonathan Edward (2006)

  • Obtaining the complete set of proteins for each eukaryotic organism is an important step in the quest to understand how life evolves and functions. The complex physiology of eukaryotic cells, however, makes direct observation of proteins and their parent genes difficult to achieve. An organism's genome provides the raw data that contains the set of instructions for generating the complete set of proteins, providing the potential to obtain a complete list of proteins without having to rely exclusively on direct observations in the cell. Computational gene prediction systems, therefore, play an important role in compiling sets of putative proteins for each sequenced genome. This dissertation addresses the problem of computational gene prediction in eukaryotic genomes, presenting a fr...

  • Thesis

  • Authors: Celic, Ivana (2006)

  • The Sir2 proteins, also known as sirtuins, represent a large and highly conserved family of NAD+-dependent protein deacetylases that control various fundamental biological proceses. The baker’s yeast, Saccharomyces cerevisiae, has five members of this family, Sir2p and Hst1-4p, important for regulation of transcriptional silencing and genomic stability. Hst3p and Hst4p are two redundant sirtuins with the major role in maintenance of genomic stablity. They control genomic stability by regulating the level of acetylation of histone H3 lysine 56. This residue, present in the core of the nucleosome surface, is acetylated during the S phase of the cel cycle and contributes to the repair proceses active during DNA replication. At the end of the S phase, K56 of histone H3 is deacetylated ...

  • Thesis

  • Authors: Lee, Hyunjoo Jean (2006)

  • Improper gonad differentiation can lead to conditions ranging from reduced fertility to sex reversal. In mammals, Sty (sex determining region, Y chromosome) initiates testis development by directing supporting cell precursors to differentiate into testicular Sertoli cells rather than ovarian granulosa cells. How ovary development is initiated is poorly understood, and we sought to gain a better understanding of fetal ovary development by identifying cell-type-specific genes that might be involved in ovarian somatic cell differentiation. Our lab previously developed Sty--EGFP transgenic mice that express enhanced green fluorescent protein uniquely in the supporting cell lineage of both male and female gonads. This transgene is the earliest known specific marker of these cells. ...