Includes copies of articles co-authored by the author during the preparation of this thesis, in back pocket. / Errata attached to back flyleaf. / Includes bibliographical references (leaves 127-139). / 139 leaves : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The results presented lend further evidence to previous work suggesting that cold shock domain factors function to repress granulocyte macrophage-colony stimulating factor transcription via DNA binding to single stranded regions across the proximal promoter. / Thesis (Ph.D.)--Adelaide University, Dept. of Medicine, 2001

Normal tissue homeostasis and appropriate responses to injury and infection are dependent on cellular communication mediated by cell surface receptors that respond to extrinsic stimuli. The GM-CSF receptor was the major focus of this project. This receptor shares a common signalling subunit, β [subscript c], with the IL-3 and IL-5 receptors. The unique GM-CSF receptor α-subunit ( GMRα ) confers ligand binding specificity to the complex and is essential for GM-CSF receptor signalling, although the full complement of signalling events mediated by GMRα remains elusive. Through cloning of candidate interacting proteins, expression and co-immunoprecipitation studies, we have confirmed interactions for two proteins previously reported to interact with the GMRα, p85 and IKKβ. Additionally, we identified the Src family kinase, Lyn, as a novel direct interacting partner of GMRα and provide insights into possible roles of this kinase in initiating signalling from the GM-CSF receptor. In addition to GMRα associated events we aimed to further characterise the role of the common β [subscript c] subunit in GM-CSF mediated signalling. We utilised two classes of consitutively active β [subscript c] mutants ( extracellular or transmembrane ) which transform the bi-potential myeloid FDB1 cell line to either factor-independent growth and survival, or granulocyte-macrophage differentiation, respectively. Here we report a comprehensive biochemical analysis of signalling by these two classes of mutants in this cell line. The two activated GMR mutants displayed distinct and non-overlapping signalling capacity. In particular, expression of a mutant with a substitution in the transmembrane domain ( V449E ) selectively activated JAK / STAT5 and MAPK pathways resulting in a high level of sensitivity to JAK and MEK inhibitors. In contrast, expression of a mutant with a 37 amino acid duplication in its extracellular domain ( FI Δ ) selectively activates the PI3K / AKT and IKKβ / NFkB pathways. Cells responding to this mutant display a relative high level of sensitivity to two independent PI3K inhibitors and relative resistance to inhibition of MEK and JAK2. The non-overlapping nature of signalling by these two activated mutants suggests that there are alternative modes of receptor activation that differentially dependent on JAK2 and that act synergistically in the mature liganded cytokine receptor complex. Further detailed analysis of these mutants will facilitate the dissection of the signalling pathways involved in the GM-CSF response that mediate proliferation, survival and differentiation. / Thesis (Ph.D.)--School of Medicine, 2007.

Thesis (Ph.D.) -- University of Adelaide, Dept. of Obstetrics and Gynaecology, 1999. / Errata posted inside back end-paper (leaf 250). Bibliography: leaves 204-249.

Thesis (Ph. D.)--University of Maryland, 1996. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Maryland, 1996. / Includes bibliographical references.

Amendments to thesis in pocket on back cover. / Copy of author's previously published article in pocket on back cover. / Bibliography: leaves 124-172. / viii, 172, [101] leaves, [22] leaves of plates : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Studies the biological effects and leukaemic potential of h[beta]c mutants using murine models. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1999?

Errata posted inside back end-paper (leaf 250). / Bibliography: leaves 204-249. / xxiv, 250 leaves, [8] leaves of plates : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Investigates the nature of the seminal vesicle-derived trigger(s) that stimulate the granulocyte-macrophage colony-stimulating factor release from the murine uterine epithelium. / Thesis (Ph.D.)--University of Adelaide, Dept. of Obstetrics and Gynaecology, 1999

Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1999? / Amendments to thesis in pocket on back cover. Copy of author's previously published article in pocket on back cover. Bibliography: leaves 124-172.

Thesis (M. Phil.)--University of Hong Kong, 2008. / Includes bibliographical references (leaf 119-147) Also available in print.

Thesis (M. Phil.)--University of Hong Kong, 2008. / Includes bibliographical references (leaf 119-147) Also available online.