Molecular and Evolutionary Properties of Non-Gene-Coding Regions in Bacteria Using Comparative Genome Bioinformatics
Year of Dissertation:
2010
Although most non-gene-coding regions of the genome have long been thought of as nonfunctional, a growing body of literature now show that many sites act as important sources of phenotypic variation and complexity. In eukaryotes, this has been attributed to the sophisticated gene regulatory apparatus that includes cis-acting regulatory elements acting on multiple levels. In bacteria, this level of regulatory multiplicity is reduced, as is reflected by the lower percentage of intergenic segments in their genomes and the lower capacity for metabolic and catabolic activities. Most non-gene-coding intergenic portion of the genome of bacteria is thought of as functionally compact, mostly transcriptional and translational regulatory in nature, containing only limited number of infrastructural or regulatory RNAs. This study addresses the extent of this cis-regulatory organization on noncoding genomic regions in the Lyme bacteria Borrelia burgdorferi as apparent in their molecular and evolutionary properties and how they can influence and be applied to the bioinformatic predictions of cis-regulatory function. Several general molecular and evolutionary properties of a bacterial non-coding genome were identified. Overall, most non-gene-coding intergenic portion of Borrelia are constrained, functionally compact and degenerate. A phylogenetic footprinting approach for very closely related species (> 90% nucleotide sequence identity) was developed to test for specific sites of transcriptional regulation, which was additionally tested using the Escherichia coli genome dataset. The method finds most constrained regions to coincide with several general properties of promoter binding, suggesting that constraint levels are differentiable even amongst these very closely related bacterial species, providing a way to measure for molecular function at a fine phylogenetic level through the understanding of the patterns of DNA sequence evolution.
Systematics of Grammitid ferns (Polypodiaceae): using a combined approach to resolve the circumscription of Melopmene, and portions of the polyphyletic genera Lellingeria and Terpsichore
Year of Dissertation:
2009
Recent phyogenetic analyses of grammitid ferns (Polypodiaceae) demonstrated that many genera recognized within this clade are not
The role of BAFF overexpression in the loss of anti-dsDNA B cell tolerance
Year of Dissertation:
2010
Overexpression of BAFF is believed to play an important role in Systemic Lupus Erythematosus and elevated levels of serum BAFF have been found in lupus patients. Excess BAFF also leads to overproduction of anti-dsDNA antibodies and a lupus-like syndrome in mice. In the present study, we use mice transgenic for the R4A-Cμ (IgMa) heavy chain of an anti-dsDNA antibody, to study the effects of BAFF overexpression on anti-dsDNA B-cell regulation. We observe that overexpression of BAFF promotes anti-dsDNA B cell maturation and secretion of antibody and enriches for transgenic anti-dsDNA B cells in the marginal zone and follicular splenic compartments. In addition, our data suggests that BAFF rescues a subset of anti-dsDNA B cells from a regulatory checkpoint in the transitional stage of development. The subset of B cells identified as transitional type 3 (T3) subset present in R4A-Cμ and R4A-Cμ/BAFF mice, exhibits an anergic phenotype and contains a high frequency of anti-dsDNA B cells. Our findings suggest that BAFF may enhance survival of this subset and promote anti-dsDNA Ab secretion in synergy with environmental stimuli such as CpG.
SURVIVAL SIGNALS IN HUMAN CANCER CELLS MEDIATED BY PHOSPHOLIPASE D AND mTOR
Year of Dissertation:
2009
Phospholipase D (PLD), which is commonly elevated in renal and other cancers, provides a survival signal that suppresses apoptosis induced by serum deprivation in renal cancer cells. Hypoxia-Inducible Factors α (HIFα), important effectors of hypoxic response, have been shown to play a pivotal role in the tumorigenesis of renal cancer cells that lack the von Hipple Lindau tumor suppressor gene (VHL), a critical mediator of HIFα proteolytic degradation. We report here a role for PLD as another regulatory component of HIFα expression in renal cancer cells where accumulation of both HIF1α and HIF2α in require functional PLD for efficient translation, independently from pVHL expression.
Using Tissue Culture as an Alternative Source of Polyphenols Produced by
Author:
George Tsalokostas
Year of Dissertation:
2009
Plants have long been used as sources of pharmaceuticals or other commercial products. Many of these products are difficult to synthesize at affordable prices. Furthermore, the extensive testing that is required of synthetic products in order to meet safety standards, compared to requirements for natural products, has stimulated interest in replacing many synthetic chemicals, especially food additives, by natural plant extracts. "Plantations" of medicinal plants, as with any cropped plants, are vulnerable to diminished yields due to outbreaks of disease or unfavorable changes in growing conditions, resulting in considerable economic loss to growers. Furthermore, some plants can not be grown as crops in the geographical areas where there is the most need for their products. In such cases, an alternative means of obtaining natural products from plants is through plant tissue culture. The fruit and leaves of Ficus carica (the edible fig) produce many polyphenolic antioxidants of potential therapeutic value. However, the plant is vulnerable to fig mosaic virus disease, and does not grow well out of semitropical and Mediterranean climates. In this work, Ficus carica tissue cultures were investigated as an alternate source of antioxidant polyphenols. It is well know that ntioxidants have anticarcinogenic, antibacterial, and antiviral properties and can be used as food supplements. In an effort to determine culture conditions that resulted in the production of polyphenols comparable to those produced by intact plants, chemical and physical factors that affect yield, such as basal media composition, light intensity, temperature, growth hormones, and elicitors were tested.
Systems biology-based study of provitamin A carotenoid biosynthesis in Arabidopsis thaliana
Year of Dissertation:
2011
Due to their great nutritional and health value, understanding the regulatory mechanisms and recognizing new points of control in the carotenoid pathway can be the goal of breeding plans for increasing carotenoids accumulation in crop plants. Systems biology is an inter-disciplinary field, which integrates computational models and tools with molecular biology and different types of data including in silico transcriptomics, co-expression correlation, metabolomics, proteomics and phylogenetic information in order to develop hypotheses with statistically sound robustness. In the first steps of my work I describes the sequential use of freely available databases to explore the regulation of carotenoid biosynthesis in Arabidopsis during chloroplast development. The findings suggested that coordinated transcriptional regulation of genes along the isoprenoid-related biosynthesis pathways, play a major role in coordinating the synthesis of functionally related, chloroplast-localized isoprenoid-derived compounds. Next I aspired to find candidate genes that are participating in or regulating the carotenoid pathway. A model was developed to integrate several types of high-throughput data, in order to optimize candidate gene ranking in an effort to best define associated genes for a specific studied pathway. The candidate ranking was achieved by using an iterative algorithm (called MORPH), which is built on implementation of machine learning techniques. Application of the method on several biological pathways in Arabidopsis proved the ability of the algorithm to capture experimentally proven gene candidates related to known biological pathways. The robustness of the predictions provided by MORPH creates an exciting research methodology to explore regulation of biological pathways in plants. Although the development of the computational algorithm was initially triggered by the specific needs of our laboratory, namely, for close analysis of the carotenoid pathway, the algorithm is suitable for almost any biological pathway in plants. Moreover the method could be applied to any other model system that has enough available high-throughput data.
Carotenogenesis in Maize Endosperm: Natural Genetic Variation as a Tool for Predictive Metabolic Engineering
Author:
Ratnakar Vallabhaneni
Year of Dissertation:
2009
Vitamin A deficiency is a global health burden. This deficiency can be alleviated through provitamin A carotenoid biofortification of maize and other Poaceae crops. However, the predictive metabolic engineering or breeding is limited by the incomplete understanding of endogenous pathway regulation. If the pathway regulation was better understood, enhancement of carotenoid biosynthesis could be controlled by limiting rate-controlling steps and timing of expression in carotenogeneic tissues.
SYSTEMATICS AND PHYLOGENY OF ELAPHOGLOSSUM SECTION LEPIDOGLOSSA (DRYOPTERIDACEAE)
Author:
Alejandra Vasco-Gutierrez
Year of Dissertation:
2010
Elaphoglossum (Dryopteridaceae) is one of the most diverse genera of ferns, yet it is noteworthy for lacking monographic studies for any of its subgroups. This study was an attempt to find clades of convenient size for monographic study within Elaphoglossum section Lepidoglossa, one of the largest sections of the genus. To do that the phylogeny of the section was investigated using three chloroplast markers. These molecular phylogenetic analyses identified 13 clades, two of which were selected for monographic revision: the Elaphoglossum ciliatum group and Elaphoglossum subsection Muscosa. The Elaphoglossum ciliatum group turned out to have nine species characterized by laminar scales reduced to minute dots, spiny perispores, and resinous rhizomes. Elaphoglossum subsection Muscosa turned out to have 15 species characterized by flat scales with acicular marginal cells, scaly laminae, and spores about twice as long as other species of Elaphoglossum. Besides constituting a framework from which to choose morphologically recognizable clades of convenient size for monographic study, the phylogeny provided important new insights into the systematics and taxonomy of Elaphoglossum section Lepidoglossa.
Fine-scale genetics, population dynamics, and management of suburban white-tailed deer (Odocoileus virginianus)
Year of Dissertation:
2012
Overabundant populations of white-tailed deer Odocoileus virginianus can cause broad declines in native biodiversity, the lack of advanced woody regeneration, and shifts in successional trajectories. These problems are especially pronounced in the suburbs of the Northeastern U.S. In the northern suburbs of New York City, land managers have begun implementing small scale (< 20 km2), bow-only hunts to reduce overabundant deer herds. The success of these controlled hunts will depend on deer socio-population dynamics, the efficacy of bow hunting, and the sustained participation of bow hunters. I used a multi-disciplinary approach to address these issues and to evaluate the utility of bow hunting as a tool for managing suburban deer.
DEVELOPMENTAL ALTERATIONS OF RAPHÉ NUCLEI IN AUTISTIC SUBJECTS 5-15 YEARS OF AGE- METHODS AND TECHNICAL LIMITATIONS
Year of Dissertation:
2013
The role of the serotonergic system in autism is supported by more than 500 reports. They reveal a link between serotonergic system alterations and social deficits, repetitive behavior, hyperactivity, anxiety and obsessive compulsive behavior observed in autism. However, in spite of evidence of altered development of brain serotonergic system and contribution of these alterations to the autism phenotype, the raphé nuclei, which are the source of brain serotonin, have not been examined.