Pseudomonas aeruginosa is an opportunistic human pathogen that infects immunocompromised individuals such as those suffering from burns or the genetic disorder cystic fibrosis. This organism utilizes a cell-cell communication mechanism known as quorum sensing (QS) to coordinate virulence gene expression and biofilm formation. It has three interconnected QS systems, namely las, rhl and pqs. Each system is comprised of autoinducer synthesis genes, lasI, rhlI, and pqsABCDH, and the cognate regulatory genes, lasR, rhlR, and pqsR, respectively. Here, we primarily focused on understanding the regulatory mechanisms of QS, which we investigated at two levels. First, we sought to identify additional activators that regulate QS at the level of the las and rhl systems, and second, we investigated the regulation of downstream genes, particularly biofilm exopolysaccharide genes, by QS. For the first approach, we employed a mutagenesis screen to identify global QS activators. We screened a non-redundant transposon library for mutants deficient in QS-dependent phenotypes. We identified a novel regulator, GidA, a glucose-inhibited cell division protein, that selectively controls QS gene expression posttranscriptionally via RhlR-dependent and –independent pathways. For the second part, we established a regulatory link between QS and Pel exopolysaccharide. We showed that the las system represses Pel and modulates colony biofilm structure through the pqs pathway. LasR mediated colony rugosity via 4-hydroxy-2-alkylquinolines in a PqsR-independent manner, ascribing a novel function to this class of signaling molecules in P. aeruginosa. Taken together, our study highlights the complexity of QS, which involves integration of various regulatory pathways to control downstream processes in response to different environmental conditions. / Graduation date: 2012

Graduation date: 1993

Thesis (M. Phil.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

Nearly one half of the human genome is composed of transposable elements (TEs). Once dismissed as 'selfish' or 'junk' DNA, TEs have also been implicated in a numerous functions that serve the needs of their host genome. I have evaluated the role of TEs in mediating the epigenetic mechanisms that serve to regulate human gene expression. These findings can be broadly divided into two major mechanisms by which TEs affect human gene expression; by modulating nucleosome binding in the promoter regions and by recruiting epigenetic histone modifications that enable them to serve as promoters and enhancers. Thus. the studies encompassed in this thesis elucidate the contributions of TEs in epigenetically regulating human gene expression on a global as well as local scale.

Thesis (Ph. D.)--University of Missouri-Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 201-225). Also available on the Internet.

Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references (p. 180-205). Also available in print.

Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references (p. 180-205). Also available online.

Thesis (Ph. D.)--University of Missouri-Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 201-225). Also available on the Internet.

Thesis (Ph. D.)--Ohio State University, 2003. / Title from first page of PDF file. Document formatted into pages; contains xii, 152 p. : ill., (some col.). Includes abstract and vita. Advisor: Anthony Young, Molecular, Cellular, and Developmental Biology Program. Includes bibliographical references (p. 137-150).

Thesis (Ph. D.)--University of Oregon, 2002. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 174-182).