Helicobacter pylori is a unique bacterial pathogen which colonises the human stomach. Infection with H. pylori has been linked to several disease outcomes including gastric and duodenal ulcer, gastric cancer and MALT lymphoma. Considering the harsh environment in which it resides and the lack of competition from other bacteria, this host/pathogen relationship is particularly interesting. Microarray analysis is a new and powerful technique which can be used to investigate various aspects of these complex interactions. Expression profiling of bacteria using microarrays remains in its infancy and thus appropriate methods were developed herein for investigating the transcriptional responses of H. pylori to various environments in vitro. Studies showed the tight relationship between growth phase dependent expression of iron homeostasis, motility and virulence genes in H. pylori for the first time. Consequently, the late exponential phase of growth was implicated as the most virulent growth phase of this bacterium in vitro. In response to mammalian cell co-culture, induced expression of H. pylori metabolism/respiration genes, genes of unknown function and genes encoding the 2-component regulators, HP1021 and HP0166, were detected. These represent a set of genes likely to be important specifically in the context of infection. To investigate the host response to infection a new mouse colonising strain of H. pylori, the Sydney Strain 2000 (SS2000), was isolated for use in comparative studies with the established strain, Sydney Strain 1 (SS1). Both host and strain specific effects were studied in a 15 month colonisation experiment using C57BL/6 and BALB/c mice. Genomic typing was used to investigate dynamic changes that occurred in the mouse-adapted strains during colonisation. In these animals reponses relating to the severity of inflammation and to the infecting H. pylori isolate were revealed by gene expression profiling. Previously unrealised cellular responses were uncovered. These included the significant down-regulation of both ferritin and haemoglobin expression. This perhaps suggests a mechanism for H. pylori induced iron deficiency anaemia. Physiological connections between colonisation, acid secretion and expression of the endocrine hormones were also implicated. These experiments have shown the utility of microarray analysis in the investigation of pathogenesis and have highlighted many directions for further investigation.

Thesis (Ph.D.) -- University of Texas at Arlington, 2008.

Thesis (M. Phil.)--Hong Kong University of Science and Technology, 2003. / Includes bibliographical references (leaves 103-111). Also available in electronic version. Access restricted to campus users.

Thesis (Ph.D.)--City University of Hong Kong, 2009. / "Submitted to Department of Biology and Chemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy." Includes bibliographical references (leaves 133-147)

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 117-135).

Thesis (Ph.D.)--University of Nebraska-Lincoln, 2009. / Title from title screen (site viewed March 2, 2010). PDF text: 100 p. : col. ill. ; 953 K. UMI publication number: AAT 3379821. Includes bibliographical references. Also available in microfilm and microfiche formats.

Thesis (M. Phil.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 79-86).

Alzheimer’s disease (AD) is one of the common diseases of older people. Although several genes have been identified for Familial Alzheimer’s Disease (FAD), a reliable diagnostic, especially for those patients in their early or intermediate phases of AD, is still not available. There is neither effective treatment nor drugs that can stop or reverse AD progression. Breakthroughs in diagnosis or treatment development likely require understanding of the molecular mechanisms of AD. Studies in FAD have shown that APP, PS1, PS2 and some other genes are related to FAD. Mutations of APP and PS1 lead to amyloid plaque accumulation which is also prominent in Sporadic AD. Transgenic animals closely mimic human AD pathologies in many aspects. A mouse model carrying both APP Swedish mutation and PS1 deltaE9 mutation is used in this study. This mouse model accumulates amyloid plaque rapidly, and the plaque shows up as early as 6 months of age. Using microarrays, we have isolated 176 genes with significant expression changes and 14 turned on/off genes from AD mouse cortex. From this cDNA microarray measurement of global gene expression, several functional groups were regulated significantly in our mouse model of AD pathology. Mt2 and Atp7a were identified and may be candidates for further studies of AD pathology, as well as potential drug targets. Five significant microRNAs were found from AD mouse cortex, providing evidence that microRNAs could play a role in AD. cDNA arrays were also used to identify potential biomarkers from whole blood samples that distinguish AD mice from their non-transgenic littermates. / text

published_or_final_version / Dentistry / Master / Master of Orthodontics

Not available / text