Thesis (MSc(R)) - University of Glasgow, 2007. / MSc(R) thesis submitted to the Faculty of Information and Mathematical Sciences, Department of Computing Science, University of Glasgow, 2007. Includes bibliographical references. Print version also available.

Thesis (Ph.D.)--Drexel University, 2010. / Includes abstract and vita. Includes bibliographical references (leaves 115-126).

<p> Trypanosomatids cause human diseases such as leishmaniasis and African trypanosomiasis. Trypanosomatids are protists from the order Trypanosomatida and include species of the genera <i>Trypanosoma</i> and <i> Leishmania</i>, which occupy a similar ecological niche. Both have digenic life-stages, alternating between an insect vector and a range of mammalian hosts. However, the strategies used to subvert the host immune system differ greatly as do the clinical outcome of infections between species. The genomes of both the host and the parasite instruct us about strategies the pathogens use to subvert the human immune system, and adaptations by the human host allowing us to better survive infections. We have applied unsupervised learning algorithms to aid visualization of amino acid sequence similarity and the potential for recombination events within <i>Trypanosoma brucei </i>'s large repertoire of variant surface glycoproteins (VSGs). Methods developed here reveal five groups of VSGs within a single sequenced genome of <i>T. brucei</i>, indicating many likely recombination events occurring between VSGs of the same type, but not between those of different types. These tools and methods can be broadly applied to identify groups of non-coding regulatory sequences within other Trypanosomatid genomes. To aid in the detection, quantification, and species identification of leishmania DNA isolated from environmental or clinical specimens, we developed a set of quantitative-PCR primers and probes targeting a taxonomically and geographically broad spectrum of <i>Leishmania</i> species. This assay has been applied to DNA extracted from both human and canine hosts as well as the sand fly vector, demonstrating its flexibility and utility in a variety of research applications. Within the host genomes, fine mapping SNP analysis was performed to detect polymorphisms in a family study of subjects in a region of Northeast Brazil that is endemic for <i>Leishmania infantum chagasi</i>, the parasite causing visceral leishmaniasis. These studies identified associations between genetic loci and the development of visceral leishmaniasis, with a single polymorphism associated with an asymptomatic outcome after infection. The methods and results presented here have capitalized on the large amount of genomics data becoming available that will improve our understanding of both parasite and host genetics and their role in human disease.</p>

Thesis (Ph.D.)--University of California, San Francisco, 2007. / Source: Dissertation Abstracts International, Volume: 68-11, Section: B, page: 7115. Adviser: Joseph DeRisi.

Thesis (Ph.D.)--University of California, San Francisco, 2008. / Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 0768. Adviser: Robert W. Mahley. Includes supplementary digital materials.

Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2006. / Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3639. Adviser: Huimin Zhao. Includes bibliographical references. Available on microfilm from Pro Quest Information and Learning.

The worldwide rise of diabetes and obesity has spurred research investigating the molecular mechanisms that mediate the deleterious effects associated with these diseases. Individuals with diabetes and/or obesity are at increased risk from a variety of health consequences, including heart attack, stroke and peripheral vascular disease; all of these complications have oxygen deprivation as the central component of their pathology. The nematode Caenorhabditis elegans has been established as a model system for understanding the genetic and molecular regulation of oxygen deprivation response, and in recent years methods have been developed to study the effects of excess glucose and altered lipid homeostasis. Using C. elegans, I investigated transcriptomic profiles of wild-type and hyl-2(tm2031) ( a ceramide biosynthesis mutant) animals fed a standard or a glucose supplemented diet. I then completed a pilot RNAi screen of differentially regulated genes and found that genes involved in the endobiotic detoxification pathway (ugt-63 and cyp-25A1) modulate anoxia response. I then used a lipidomic approach to determine whether glucose feeding or mutations in the ceramide biosynthesis pathway or the insulin-like signaling pathway impact lipid profiles. I found that gluocose alters the lipid profile of daf-2(e1370) (an insulin-like receptor mutant) animals. These studies indicate that a transcriptomic approach can be used to discover novel pathways involved in oxygen deprivation response and further validate C. elegans as a model for understanding diabetes and obesity.