UMD Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/3
New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a given thesis/dissertation in DRUM.
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Item Structural Variants of AI-2 Analogs to Probe Quorum Sensing in Diverse Bacteria(2011) Gamby, Sonja Josette; Sintim, Herman O.; Master of Life Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Bacterial infections which were once easily managed with antibiotics are now reemerging as a serious threat to human health. The difficulty in managing infectious diseases is arising out of bacterial resistance to front line antibiotics. A new paradigm for fighting bacterial infection via the inhibition of quorum sensing has emerged. Quorum sensing is the process by which small diffusible molecules (autoinducers) are used to sense population density and upregulate genes. Notably, genes for virulence production and biofilm formation have been found to be controlled by this process. Thus, quorum sensing, offers an alternative target for the treatment of bacterial infections. One autoinducer which has been identified across many bacterial species is AI-2. The goals of this thesis were to make more hydrolytically stable analogs of AI-2 as potent inhibitors of quorum sensing, as well as, exploring the effects of AI-2 analogs on QS in P. aeruginosa. In this study, the processing of bis ester protected AI-2 analogs was examined. Also, two long chain AI-2 analogs were synthesized and tested for their ability to inhibit QS in P.aeruginosa. It was found that bis protected analogs are processed different across bacterial species. Also, long chain AI-2 analogs were found to be inhibitors of QS in P. aeruginosa, specifically, by inhibiting a LasR receptor which typically responds to a different class of autoinducer.Item Biological Nanofactories: Altering Cellular Response via Localized Synthesis and Delivery(2008-11-19) Fernandes, Rohan; Bentley, William E; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Conventional research in targeted delivery of molecules-of-interest involves either packaging of the molecules-of-interest within a delivery mechanism or pre-synthesis of an inactive prodrug that is converted to the molecule-of-interest in the vicinity of the targeted area. Biological nanofactories provide an alternative approach to targeted delivery by locally synthesizing and delivering the molecules-of-interest at surface of the targeted cells. The machinery for synthesis and delivery is derived from the targeted cells themselves. Biological nanofactories are nano-dimensioned and are comprised of multiple functional modules. At the most basic level, a biological nanofactory consists of a cell targeting module and a synthesis module. When deployed, a biological nanofactory binds to the targeted cell surface and locally synthesizes and delivers molecules-of-interest thus altering the response of the targeted cells. In this dissertation, biological nanofactories for the localized synthesis and delivery of the 'universal' quorum sensing signaling molecule autoinducer-2 are demonstrated. Quorum sensing is process by which bacterial co-ordinate their activities at a population level through the production, release, sensing and uptake of signaling autoinducers and plays a role in diverse bacterial phenomena such as bacterial pathogenicity, biofilm formation and bioluminescence. Two types of biological nanofactories; magnetic nanofactories and antibody nanofactories are presented in this dissertation as demonstrations of the biological nanofactory approach to targeted delivery. Magnetic nanofactories consist of the AI-2 biosynthesis enzymes attached to functionalized chitosan-mag nanoparticles. Assembly of these nanofactories involves synthesis of the chitosan-mag nanoparticles and subsequent assembly of the AI-2 pathway enzymes onto the particles. Antibody nanofactories consist of the AI-2 biosynthesis enzymes self assembled onto the targeting antibody. Assembly of these nanofactories involves creation of a fusion protein that attaches to the targeting antibody. When added to cultures of quorum sensing bacteria, the nanofactories bind to the surface of the targeted cells via the targeting module and locally synthesize and deliver AI-2 there via the synthesis module. The cells sense and uptake the AI-2 and alter their natural response. Prospects of using biological nanofactories to alter the native response of targeted cells to a 'desired' state, especially with respect to down-regulating undesirable co-ordinated bacterial response, are envisioned.