+publisher:"University of Adelaide" +contributor:("School of Molecular and Biomedical Science")

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1. Vink, Robert. [Uncovering the critical roles of magnesium and substance P in central nervous system injury].

Degree: 2013, University of Adelaide

URL: http://hdl.handle.net/2440/80409

► Dot Point Summary . First to apply phosphorus magnetic resonance spectroscopy to the study of traumatic brain injury (TBl) and spinal cord injury (SCl) -… (more)

▼ Dot Point Summary . First to apply phosphorus magnetic resonance spectroscopy to the study of traumatic brain injury (TBl) and spinal cord injury (SCl) - led to a complete description of high energy phosphate metabolism after CNS trauma - led to the co-development of the lateral fluid percussion model of rodent TBI - was the first in vivo demonstration that brain trauma was different from ischaemia - identified that energy metabolism differed between brain and spinal cord injury . First to apply proton magnetic resonance spectroscopy (MRS) to the study of TBI and SCI - identified that lactate concentration did not reach injury thresholds after brain trauma - first described that n-acetyl-aspartate was an unsuitable MRS concentration standard after brain injury - first described that n-acetyl-aspartate declined after brain injury . Discovered that brain magnesium concentration declined after TBI - a seminal demonstration that intracellular free magnesium concentration can change in vivo - first to demonstrate that tissue total magnesium can decline after injury - first to calculate the impact of magnesium change on critical bioenergetic parameters in vivo - first to measure altered mitochondrial bioenergetics after TBI . Discovered that magnesium treatment improved outcome after TBI - first description of magnesium as a neuroprotective agent after acute brain injury - first to demonstrate that lowering magnesium concentration was deleterious to outcome - first to demonstrate a dose-response effect for magnesium and define the therapeutic window after TBI . First to apply diffusion weighted imaging to the study of TBI - identified critical early phase of vasogenic oedema following trauma . Discovered that neuropeptides, and in particular substance P, are involved in early oedema formation after TBI and stroke - first to identify neurogenic inflammation as a characteristic feature of acute brain injury - first to describe NK1 antagonists as a novel therapeutic approach to treat oedema - first to describe beneficial effects of combined NK1 antagonists and tPA in stroke - first to describe the efficacy of NK1 antagonists in management of intracranial pressure . Discovered that substance P may play a critical role in cell death in early Parkinson's disease - first to describe NK1 antagonists as a novel therapeutic approach to treat Parkinson's disease . Over 6,500 citations according to Google Scholar . "h" index of 41 . Associate Editor for the journal, Magnesium Research . 0n the editorial boards of Journal of Neurotrauma, Neurotherapeutics and Frontiers in Neurotrauma Advisors/Committee Members: School of Molecular and Biomedical Science (school).

Subjects/Keywords: magnesium; substance P; nervous; brain injury

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APA (6^th Edition):

Vink, R. (2013). [Uncovering the critical roles of magnesium and substance P in central nervous system injury]. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/80409

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Vink, Robert. “[Uncovering the critical roles of magnesium and substance P in central nervous system injury].” 2013. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/80409.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Vink, Robert. “[Uncovering the critical roles of magnesium and substance P in central nervous system injury].” 2013. Web. 22 Feb 2020.

Vancouver:

Vink R. [Uncovering the critical roles of magnesium and substance P in central nervous system injury]. [Internet] [Thesis]. University of Adelaide; 2013. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/80409.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Vink R. [Uncovering the critical roles of magnesium and substance P in central nervous system injury]. [Thesis]. University of Adelaide; 2013. Available from: http://hdl.handle.net/2440/80409

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

2. McColl, Shaun Reuss. Regulation of cell activation and migration by chemotactic factors: collected publications 1988-2011.

Degree: 2013, University of Adelaide

URL: http://hdl.handle.net/2440/80407

► The human body is protected from harmful infection by a number of cellular and humoral factors that are involved in a wide range of complex… (more)

Subjects/Keywords: cell activation; migration; chemotactic factors; cellular; humoral

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APA (6^th Edition):

McColl, S. R. (2013). Regulation of cell activation and migration by chemotactic factors: collected publications 1988-2011. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/80407

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

McColl, Shaun Reuss. “Regulation of cell activation and migration by chemotactic factors: collected publications 1988-2011.” 2013. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/80407.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

McColl, Shaun Reuss. “Regulation of cell activation and migration by chemotactic factors: collected publications 1988-2011.” 2013. Web. 22 Feb 2020.

Vancouver:

McColl SR. Regulation of cell activation and migration by chemotactic factors: collected publications 1988-2011. [Internet] [Thesis]. University of Adelaide; 2013. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/80407.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

McColl SR. Regulation of cell activation and migration by chemotactic factors: collected publications 1988-2011. [Thesis]. University of Adelaide; 2013. Available from: http://hdl.handle.net/2440/80407

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

3. Mabarrack, Nicholas Harry Edward. The recent thymic origin, differentiation and suppressive mechanism of regulatory T cells.

Degree: 2013, University of Adelaide

URL: http://hdl.handle.net/2440/84963

► Regulatory T cells are a purported lineage of CD4⁺ cells that inhibit the proliferation and effector functions of other T cells to prevent the development… (more)

▼ Regulatory T cells are a purported lineage of CD4⁺ cells that inhibit the proliferation and effector functions of other T cells to prevent the development of autoimmune disease. However, little is known about how they arise, their lifespan and their patterns of recirculation. Furthermore, the mechanisms through which they inhibit other T cells remain unclear. In order to address these issues, we investigated the relationship between regulatory T cells and recent thymic emigrants (RTE) which are newly formed T cells released into the periphery from the thymus. The CD25⁺ Foxp3⁺ regulatory T cell subset was found to be closely associated with RTE, and generated the CD25⁻ Foxp3⁺ T regulatory T cell subset by unidirectional differentiation. This process was exploited to mature flow sorted CD4⁺ CD25bright[bright in superscript]Foxp3⁺ T cells into CD25⁻ Foxp3⁺ T cells and determine that they retain their functional suppressive activity. The phenotype and physiology of the CD25⁺ Foxp3⁺ and CD25⁻ Foxp3⁺ regulatory T cell subsets were characterised and compared to conventional T cell subsets, revealing the differential expression of numerous key molecules. The high expression of CD62L and LFA-1 by CD25⁺ Foxp3⁺ regulatory T cells was consistent with both their relative enrichment within secondary lymphoid tissues and their sessile nature. The profile of adhesion molecules on the surface of CD25⁻ Foxp3⁺ cells suggested they may tend to localise to sites of inflammation other than the lamina propria, as they have a low expression of CD103 and CD62L, but high expression of LFA-1. However, CD25⁻ Foxp3⁺ regulatory T cells were found to selectively migrate into the intestinal mucosa, where they were enriched, and they also returned back to the thymus, suggesting they may constitute a tissue homing subset of regulatory T cells. We explored the mechanism of regulatory T cell suppression, and found that regulatory T cells condition APC to reduce their ability to activate other T cells. Following the application of this system to differential gene expression microarray analysis, we identified several putative molecular targets of regulation including 10 novel predicted serine/threonine kinases, a novel four point-1, ezrin, radixin and moesin domain containing signalling molecule, the E2F transcription factor 5, and a CD163-like molecule. Aging was found to negatively affect the productivity of the thymus, although it was found to be still generating new T cells into old age. While the number of thymocytes decreased with aging, the number of Foxp3⁺ cells in the thymus was unaffected, possibly their preferential recirculation back to the thymus. The size of the peripheral T cell pool decreased with aging, and the proportion of CD25⁺ Foxp3⁺ regulatory T cells among CD4+ T cells declined. However, the proportion of CD25⁻ Foxp3⁺ regulatory T cells increased with aging in the periphery. The conversion of CD25⁺ Foxp3⁺ regulatory T cells into CD25⁻ Foxp3⁺ T cells may compensate for the declining thymic output of CD25⁺ Foxp3⁺ regulatory T cells… Advisors/Committee Members: Mayrhofer, Graham (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: regulatory T cells; immunology

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APA (6^th Edition):

Mabarrack, N. H. E. (2013). The recent thymic origin, differentiation and suppressive mechanism of regulatory T cells. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/84963

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Mabarrack, Nicholas Harry Edward. “The recent thymic origin, differentiation and suppressive mechanism of regulatory T cells.” 2013. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/84963.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Mabarrack, Nicholas Harry Edward. “The recent thymic origin, differentiation and suppressive mechanism of regulatory T cells.” 2013. Web. 22 Feb 2020.

Vancouver:

Mabarrack NHE. The recent thymic origin, differentiation and suppressive mechanism of regulatory T cells. [Internet] [Thesis]. University of Adelaide; 2013. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/84963.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Mabarrack NHE. The recent thymic origin, differentiation and suppressive mechanism of regulatory T cells. [Thesis]. University of Adelaide; 2013. Available from: http://hdl.handle.net/2440/84963

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

4. Lum, Mabel Yuen Teng. Identification of host cell proteins involved in Shigella flexneri pathogenesis.

Degree: 2014, University of Adelaide

URL: http://hdl.handle.net/2440/87369

► Shigella flexneri is the etiological agent of bacillary dysentery (shigellosis). It is transmitted via the faecal-oral route and is a significant human pathogen due to… (more)

▼ Shigella flexneri is the etiological agent of bacillary dysentery (shigellosis). It is transmitted via the faecal-oral route and is a significant human pathogen due to the high morbidity among children <5 years in developing countries. The key pathogenic features of Shigella include cell death induction in myeloid immune cells and circumventing cell death in colonic epithelial cells, the site of bacterial infection. Shigella also interact with host proteins to initiate de novo actin synthesis to facilitate its intra- and intercellular spread to disseminate in the host. In this thesis, the role of three host proteins: myosin IIA, dynamin II, and dynamin-related protein 1 (Drp1) during Shigella cell-to-cell spreading was examined. The myosin IIA specific kinase, myosin like chain kinase (MLCK), was previously shown to be important for Shigella plaque formation. Myosin IIA and MLCK have also been implicated in septin caging of non-motile Shigella which are targeted for degradation. Chemical inhibition and siRNA knockdown of myosin IIA reduced Shigella plaque formation. Curiously HeLa cells infected with Shigella mutants defective in cell-to-cell spreading have significantly reduced myosin IIA levels when quantified by immunofluorescence microscopy. Dynamin II and Drp1 are members of the dynamin superfamily. Both proteins have self-assembly driven GTPase activation. Dynamin II is important for clathrin-mediated endocytosis and pinches the budding clathrin-coated vesicle, and Drp1 is essential for mitochondrial fission. It was hypothesized that Shigella protrusion formation into adjacent host cells resembles endocytic and exocytic processes, and components of these processes may facilitate Shigella dissemination. When dynamin II GTPase was inhibited with dynasore and dynamin II was knocked down with siRNA, Shigella cell-to-cell spreading was significantly reduced. The in vivo efficacy of dynasore was tested in a murine Sereny model. No significant reduction in inflammation was observed but mice were protected against weight loss during infection. Further experimentation suggested dynasore protected mice against cytotoxic effects from the three secretion system (TTSS) effectors expressed by Shigella during infection. Drp1 was investigated in this thesis as dynasore also inhibits the GTPase of this mitochondrial fission protein. Mitochondrial fission is important in maintaining mitochondrial dynamics and also in events downstream of intrinsic apoptosis and programmed necrosis pathways activation. Loss of mitochondrial function in Shigella-induced epithelial cell death has been reported previously. Hence the role of Drp1 in Shigella plaque formation and HeLa death was examined with the Drp1-specific inhibitor, Mdivi-1, and siRNA knockdown. HeLa cell death was significantly reduced; suggesting loss of mitochondrial function observed previously may now be attributed to Drp1 and subsequent Drp1-mediated mitochondrial fission. The impairment in Shigella cell-to-cell spreading in the absence of Drp1 suggests maintaining an intact… Advisors/Committee Members: Morona, Renato (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: Shigella; pathogenesis; endocytosis; inhibitors; cell-to-cell spreading; apoptosis; necrosis; sereny; dynasore; dynamin

…University of Adelaide and where applicable, any partner institution responsible for the joint…

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APA (6^th Edition):

Lum, M. Y. T. (2014). Identification of host cell proteins involved in Shigella flexneri pathogenesis. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/87369

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lum, Mabel Yuen Teng. “Identification of host cell proteins involved in Shigella flexneri pathogenesis.” 2014. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/87369.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lum, Mabel Yuen Teng. “Identification of host cell proteins involved in Shigella flexneri pathogenesis.” 2014. Web. 22 Feb 2020.

Vancouver:

Lum MYT. Identification of host cell proteins involved in Shigella flexneri pathogenesis. [Internet] [Thesis]. University of Adelaide; 2014. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/87369.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lum MYT. Identification of host cell proteins involved in Shigella flexneri pathogenesis. [Thesis]. University of Adelaide; 2014. Available from: http://hdl.handle.net/2440/87369

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

5. Teh, Min Yan. Analysis of Shigella flexneri cell surface virulence factors.

Degree: 2013, University of Adelaide

URL: http://hdl.handle.net/2440/80722

► The IcsA autotransporter (AT) is a key virulence protein of Shigella flexneri, a human pathogen that causes bacillary dysentery through invasion of colonic epithelium. IcsA… (more)

▼ The IcsA autotransporter (AT) is a key virulence protein of Shigella flexneri, a human pathogen that causes bacillary dysentery through invasion of colonic epithelium. IcsA is a polarly distributed, outer membrane protein that confers motility to intracellular bacteria by engaging the host actin regulatory protein, neural Wiskott-Aldrich syndrome protein (NWASP). The activated N-WASP in turn activates Arp2/3 complex, which initiates de novo actin nucleation and polymerisation to form F-actin comet tails and allow actin-based motility (ABM). The N-terminal surface-exposed IcsA passenger -domain (aa 53-758) is responsible for N-WASP interaction, where multiple IcsA regions: aa 185-312 (N-WASP interacting region [IR] I), aa 330-382 (N-WASP IR II) and aa 508-730 (N-WASP IR III), have been suggested to be interacting with N-WASP from previous linker-insertion mutagenesis (IcsAi). A putative autochaperone (AC) region (aa 634-735) located at the C-terminal end of IcsA passenger domain, which forms part of the self-associating AT (SAAT) domain, has been suggested to be required for IcsA biogenesis. IcsAi proteins with linker insertion mutations within the AC region had a significant reduction in production when expressed in smooth lipopolysaccharide (S-LPS) S. flexneri. This thesis investigated the biogenesis of IcsA, seeking to identify factors that affect IcsA AC mutant production in the S-LPS background. IcsAi AC mutant production was restored to a wild-type comparable levels in the rough LPS (R-LPS) S. flexneri (that lack the O-antigen component). The same phenotypes were observed in S. flexneri (both S-LPS and R-LPS) expressing site-directed mutagenised IcsA AC protein (aa 716-717). Various approaches were performed to identify the factors that caused different IcsA AC mutant production between SLPS and R-LPS S. flexneri. Both LPS Oag and DegP (a periplasmic chaperone/protease) were identified to affect IcsA AC mutant production in S-LPS strain, as the IcsA AC mutant production was restored in S. flexneri ΔdegP S-LPS strain. In addition, site-directed mutagenesis of residues Y716 and D717 within the AC region showed that these residues are critical for IcsA production and/or stability in the S-LPS background but not in the R-LPS background. Another aim of this work was to further define N-WASP IRs II and III via site-directed mutagenesis of specific amino acids. Mutant IcsA protein production level, N-WASP recruitment and F-actin comet tail formation by S-LPS and R-LPS S. flexneri were characterised. Residues 330-331, and residue 382 within N-WASP IR II, and residues 716- 717 within N-WASP IR III, were identified to be involved in N-WASP recruitment. It was shown for the first time that N-WASP activation involves interaction with different regions on different IcsA molecules and hence that oligomeric IcsA is needed for this interaction. Various “GFP-N-WASP” sub-domain proteins and IcsA protein were over-expressed, purified and used in protein binding assays. These provided preliminary data for protein binding assays… Advisors/Committee Members: Morona, Renato (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: Shigella flexneri; autotransporter; IcsA; N-WASP

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Teh, M. Y. (2013). Analysis of Shigella flexneri cell surface virulence factors. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/80722

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Teh, Min Yan. “Analysis of Shigella flexneri cell surface virulence factors.” 2013. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/80722.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Teh, Min Yan. “Analysis of Shigella flexneri cell surface virulence factors.” 2013. Web. 22 Feb 2020.

Vancouver:

Teh MY. Analysis of Shigella flexneri cell surface virulence factors. [Internet] [Thesis]. University of Adelaide; 2013. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/80722.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Teh MY. Analysis of Shigella flexneri cell surface virulence factors. [Thesis]. University of Adelaide; 2013. Available from: http://hdl.handle.net/2440/80722

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

6. Grabowicz, Marcin. Biogenesis of Shigella flexneri IcsA protein.

Degree: 2010, University of Adelaide

URL: http://hdl.handle.net/2440/63498

► The IcsA autotransporter is a vital virulence factor for Shigella flexneri, a humanspecific causative agent of bacillary dysentery that accounts for over a million global… (more)

▼ The IcsA autotransporter is a vital virulence factor for Shigella flexneri, a humanspecific causative agent of bacillary dysentery that accounts for over a million global deaths annually. Ingested Shigellae invade and spread throughout the colonic epithelium. IcsA confers motility to intracellular bacteria by engaging host actin regulatory proteins to polymerise filaments of actin in a processes termed actin-based motility. This IcsA-dependent motility potentiates the intercellular spreading. IcsA is displayed at one pole of the bacterium, thereby providing a functional focus for actin polymerisation that generated propulsive force. This work investigated the biogenesis of IcsA, seeking to identify factors that direct the cytoplasmic deliver of the nascent protein towards the pole. A refined polar targeting region, IcsA₅₃₂₋₅₇₀ has been identified. Additionally, insertion mutant, i532 and i563, within the recognised targeting sequence IcsA₅₀₆₋₆₂₀ that have been identified that are defective, though not entirely deficient, in polar targeting. GFP+ fusions to these mutated targeting sequences revealed rapid motion of fluorescent foci throughout the cytoplasm, a process that likely precedes polar targeting in the wild-type. The delivery of the polarly targeted IcsA₅₀₆₋₆₂₀ region was shown to occur contemporaneously with segregating origins of chromosomal replication (oriC) and likely shares a common cell cycle cue. The diffusive properties of exported IcsA in outer-membrane have also been investigated, addressing whether the protein diffuses in the outer membrane or is masked by LPS. To directly observe the behaviour of IcsA soon after it appears at the cell surface, a strategy exploiting metabolic biotinylation was developed and used to rapidly and specifically label nascent IcsA in the outer membrane. In further investigation of the IcsA-LPS interplay, the profile of polar LPS was shown to be uniform in comparison to the lateral cell body in S. flexneri. Reciprocal co-purification presented biochemical evidence that confirmed IcsAIcsA interactions in the outer-membrane, supporting functional oligomerisation of IcsA in the outer-membrane. Advisors/Committee Members: Morona, Renato (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: Shigella; flexneri; IcsA; autotransporter; polarity

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Grabowicz, M. (2010). Biogenesis of Shigella flexneri IcsA protein. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/63498

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Grabowicz, Marcin. “Biogenesis of Shigella flexneri IcsA protein.” 2010. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/63498.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Grabowicz, Marcin. “Biogenesis of Shigella flexneri IcsA protein.” 2010. Web. 22 Feb 2020.

Vancouver:

Grabowicz M. Biogenesis of Shigella flexneri IcsA protein. [Internet] [Thesis]. University of Adelaide; 2010. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/63498.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Grabowicz M. Biogenesis of Shigella flexneri IcsA protein. [Thesis]. University of Adelaide; 2010. Available from: http://hdl.handle.net/2440/63498

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

7. Haylock-Jacobs, Sarah. The role of class IA P13Kơ in experimental autoimmune encephalomyelitis.

Degree: 2010, University of Adelaide

URL: http://hdl.handle.net/2440/64588

► Through its role in cells of haematopoietic origin, the class IA phosphoinositide 3-kinase delta (PI3Kδ) has a significant impact on both the cell-mediated and innate… (more)

▼ Through its role in cells of haematopoietic origin, the class IA phosphoinositide 3-kinase delta (PI3Kδ) has a significant impact on both the cell-mediated and innate arms of the immune system. The catalytic protein subunit of PI3Kδ, p110δ, has been implicated in leukocyte activation and survival, Th1 and Th2 differentiation as well as the development of autoimmunity in a model of rheumatoid arthritis. While the impact of p110δ inactivation in vitro is becoming clearer, the precise role that p110δ plays in vivo remains poorly understood, particularly in regard to Th17 differentiation and models of autoimmunity. Here, using mice that express a catalytically inactive form of p110δ (p110δD910A/D910A mice) it is shown that functional p110δ is required for full expression of experimental autoimmune encephalomyelitis (EAE), a Th17-dependent model of the human autoimmune disease multiple sclerosis (MS). In p110δ-inactivated mice, T and B cell activation and function during EAE were markedly reduced, and fewer T and B cells were observed in the central nervous system (CNS) throughout disease. Th17 cell generation was demonstrably more dependent on p110δ than was the Th1 response. The decrease in T cell activation was not due to a defect in dendritic cell (DC) function because p110δ-inactivated DCs migrated, became activated and presented antigen normally. However, there was a significant increase in the proportion of T and B lymphocytes undergoing apoptosis at early stages of EAE. Due to the promising findings observed in the p110δD910A/D910A mice, the ability of the p110δ inhibitor, IC87114, to reduce EAE pathogenesis was investigated. While IC87114 was shown to be a potent inhibitor of Th1 and Th17 activation and differentiation in vitro, administration of this compound failed to reduce EAE disease under the dosing regimen used. Despite this, these findings indicate that p110δ plays an important role in the development of IL-17-dependent inflammation and suggest that small molecule inhibitors for p110δ may be useful therapeutics for the treatment of IL-17-driven pathologies. Advisors/Committee Members: McColl, Shaun Reuss (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: P13-kinase; experimental autoimmune encephalomyelitis; EAE

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APA (6^th Edition):

Haylock-Jacobs, S. (2010). The role of class IA P13Kơ in experimental autoimmune encephalomyelitis. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/64588

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Haylock-Jacobs, Sarah. “The role of class IA P13Kơ in experimental autoimmune encephalomyelitis.” 2010. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/64588.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Haylock-Jacobs, Sarah. “The role of class IA P13Kơ in experimental autoimmune encephalomyelitis.” 2010. Web. 22 Feb 2020.

Vancouver:

Haylock-Jacobs S. The role of class IA P13Kơ in experimental autoimmune encephalomyelitis. [Internet] [Thesis]. University of Adelaide; 2010. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/64588.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Haylock-Jacobs S. The role of class IA P13Kơ in experimental autoimmune encephalomyelitis. [Thesis]. University of Adelaide; 2010. Available from: http://hdl.handle.net/2440/64588

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

8. Leclercq, Tamara Marie. Regulation of sphingosine kinase by interacting proteins.

Degree: 2010, University of Adelaide

URL: http://hdl.handle.net/2440/64752

► Sphingosine kinase 1 (SK1) is responsible for phosphorylating the lipid sphingosine, generating the bio-active phospholipid, sphingosine 1-phosphate (S1P). Cells possess basal SK1 activity which has… (more)

▼ Sphingosine kinase 1 (SK1) is responsible for phosphorylating the lipid sphingosine, generating the bio-active phospholipid, sphingosine 1-phosphate (S1P). Cells possess basal SK1 activity which has been proposed to serve in a ‘housekeeping’ function to limit the levels of proapoptotic sphingosine and ceramide in the cell. In some circumstances, however, such as cell exposure to growth factors and cytokines this basal level of SK1 activity is increased, resulting in an increased production of S1P. As S1P is a pro-proliferative, pro-survival molecule, its increased production is associated with enhanced cell proliferation, survival and an oncogenic phenotype. The Pitson laboratory has shown previously that one mechanism by which SK1 is activated is through phosphorylation at Ser-225 by ERK1/2. Here, my studies focused on alternative mechanisms of SK1 activation that arise through its interaction with two proteins, eukaryotic elongation factor 1A (eEF1A) and a relatively uncharacterised protein, SK activator molecule 1 (SKAM). eEF1A is able to directly increase the catalytic activity of SK1 in vitro and is also able to increase endogenous SK activity when over-expressed in quiescent cells that have reduced levels of endogenous eEF1A protein. Due to the abundance of eEF1A protein within a cell, I hypothesized that the effect of eEF1A on SK activity may be dynamically regulated. eEF1A contains a ‘G protein-like’ domain that enables it to bind GDP and GTP. When bound by GTP, eEF1A undergoes a large conformational change that enables it to bind aminoacyltRNA for transport to the ribosome. Similarly, just as the nucleotide-bound state of eEF1A regulates its role in protein synthesis, I found that the nucleotide-bound state of eEF1A also regulates its ability to activate SK1. Strikingly, it is only the translationally inactive eEF1A.GDP that can activate SK1. A truncated form of eEF1A named PTI-1 has been described that lacks the ‘G protein-like’ domain and thus can not bind guanine nucleotides, rendering it structurally analogous to eEF1A.GDP. In keeping with my finding that only eEF1A.GDP activates SK1, I found that PTI-1 also activates SK1 both in vitro and in cells. Importantly, PTI-1 has been previously characterized as an oncoprotein and for the first time my studies have shown a likely mechanism by which PTI-1 induces a tumourigenic phenotype. Expression of PTI-1 in NIH 3T3 cells induces neoplastic transformation, as measured by focus formation. Notably, this PTI-1-induced transformation is blocked when cells are treated with SK inhibitors or when cells are co-transfected with PTI-1 and a dominant negative SK1, indicating that oncogenesis by PTI-1 is mediated through SK1. The current study also investigated the regulation of SK1 activity by its interaction with SKAM1. Previous studies have shown that SKAM1, like eEF1A, can directly increase the catalytic activity of SK1 in vitro and in cells. My studies have determined the minimal region of interaction of SKAM1 that is still able to interact with and activate SK1.… Advisors/Committee Members: Pitson, Stuart Maxwell (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: sphingosine kinase; sphingosine-1-phosphate; elongation factor 1A; sphingosine kinase activator molecule; prostate tumour inducer; translationally controlled tumour protein; cancer

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Leclercq, T. M. (2010). Regulation of sphingosine kinase by interacting proteins. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/64752

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Leclercq, Tamara Marie. “Regulation of sphingosine kinase by interacting proteins.” 2010. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/64752.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Leclercq, Tamara Marie. “Regulation of sphingosine kinase by interacting proteins.” 2010. Web. 22 Feb 2020.

Vancouver:

Leclercq TM. Regulation of sphingosine kinase by interacting proteins. [Internet] [Thesis]. University of Adelaide; 2010. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/64752.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Leclercq TM. Regulation of sphingosine kinase by interacting proteins. [Thesis]. University of Adelaide; 2010. Available from: http://hdl.handle.net/2440/64752

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

9. Jarman, Kate Elizabeth. Regulation of sphingosine kinase 1 signalling by calcium- and integrin-binding proteins.

Degree: 2010, University of Adelaide

URL: http://hdl.handle.net/2440/65139

► Sphingosine kinase 1 (SK1) catalyses the conversion of sphingosine to sphingosine-1-phosphate (S1P). Since elevated levels of cellular S1P have a well characterised prosurvival, pro-proliferative and… (more)

▼ Sphingosine kinase 1 (SK1) catalyses the conversion of sphingosine to sphingosine-1-phosphate (S1P). Since elevated levels of cellular S1P have a well characterised prosurvival, pro-proliferative and oncogenic effect in cells, the regulation of SK1 activity is the subject of much current focus. Cells typically have low basal levels of SK1 activity, which appears to have a 'housekeeping’ role in the sphingomyelin cycle. However, the catalytic activity of this enzyme can be increased by a number of growth factors, cytokines and other agonists, generating a greater pool of S1P, which then appears to be involved in its cellular signalling. The Pitson group have previously demonstrated that the agonist-induced activation of human SK1 is mediated through phosphorylation of this enzyme at Ser²²⁵. Following this phosphorylation, SK1 translocates from the cytosol to the plasma membrane, with both of these events critical for the pro-survival, anti-apoptotic and oncogenic effects of this enzyme. Prior to the current study, the mechanism for the rapid, agonist-induced translocation of SK1 to the plasma membrane remained undetermined. Previous studies have demonstrated the requirement of the calmodulin binding site in SK1 for this translocation event, however a direct requirement for calmodulin itself has yet to be shown. In this study, we show that calcium- and integrin-binding protein 1 (CIB1), a calmodulinlike molecule, mediates the agonist-induced translocation of SK1 to the plasma membrane. We also demonstrate the ability of CIB1 to act as calcium-myristoyl switch, providing a functional mechanism by which it can mediate SK1 localisation to the plasma membrane. In addition, CIB1 was shown to be critical for the agonist-induced production of S1P and also the anti-apoptotic signalling associated with SK1. Furthermore, CIB1 itself was shown to be potentially oncogenic, and a dominant-negative version of CIB1 was also able to inhibit H-Ras-induced oncogenesis. These studies have also investigated the three other members of the CIB family of proteins, CIB2, CIB3 and CIB4 and their roles in regulating SK1 localisation and subsequent signalling events. While CIB1 was critical for the agonist-induced translocation of SK1 to the plasma membrane, CIB2 acted in an opposite manner, blocking the translocation of this enzyme. Furthermore, expression of CIB2 enhanced cellular apoptosis, presumably through its inhibitory effects on the SK1 survival pathway. In addition, CIB2 blocked H-Ras mediated oncogenesis. Hence, CIB1 and CIB2 appear to have opposing roles in the cell in relation to the regulation of SK1 signalling. CIB3 and CIB4 also appeared to interact with SK1 in vitro, however the cellular function of these interactions was not elucidated in this study. Interestingly, despite having considerable sequence similarity to CIB1 and CIB2, neither protein acted in a similar manner to either CIB1 or CIB2 with respect to SK1 function. While CIB3 did not appear to have any role in the SK1 signalling pathway, studies suggested CIB4 likely to… Advisors/Committee Members: Pitson, Stuart Maxwell (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: sphingosine kinase 1; sphingosine-1-phosphate; CIB1; calcium-myristoyl switch; translocation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Jarman, K. E. (2010). Regulation of sphingosine kinase 1 signalling by calcium- and integrin-binding proteins. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/65139

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Jarman, Kate Elizabeth. “Regulation of sphingosine kinase 1 signalling by calcium- and integrin-binding proteins.” 2010. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/65139.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Jarman, Kate Elizabeth. “Regulation of sphingosine kinase 1 signalling by calcium- and integrin-binding proteins.” 2010. Web. 22 Feb 2020.

Vancouver:

Jarman KE. Regulation of sphingosine kinase 1 signalling by calcium- and integrin-binding proteins. [Internet] [Thesis]. University of Adelaide; 2010. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/65139.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Jarman KE. Regulation of sphingosine kinase 1 signalling by calcium- and integrin-binding proteins. [Thesis]. University of Adelaide; 2010. Available from: http://hdl.handle.net/2440/65139

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

10. Jolly, Lachlan. The deubiquitylating enzyme USP9X promotes the polarity and self-renewal of neural progenitor cells.

Degree: 2010, University of Adelaide

URL: http://hdl.handle.net/2440/65477

► Neural Progenitor Cells (NPCs) are the primordial cells of central nervous system (CNS). Understanding how they are regulated benefits our knowledge of normal development, the… (more)

▼ Neural Progenitor Cells (NPCs) are the primordial cells of central nervous system (CNS). Understanding how they are regulated benefits our knowledge of normal development, the pathology of neurological disorders, and of therapeutic designs. One gene identified as a putative regulator of stem cell (SC) populations, including NPCs, by virtue of displaying commonly elevated expression in representative SC populations is USP9X. During development, USP9X mRNA is found highly expressed in the ventricular zones of the developing murine CNS. On this basis the USP9X protein, a substrate specific deubiquitylating enzyme, was hypothesized to be highly expressed in NPCs, and to function in the control of NPC behavior. USP9X protein was found enriched within the apical end-feet structures of NPCs, where it partially co-localised with N-cadherin. This expression domain is common to highly conserved NPC polarity imparting complexes, and to fate determinant networks, which are functionally integrated together to control NPC fate. Thus USP9X protein expression was consistent with a putative regulatory role in NPC fate. To identify cellular processes regulated by USP9X in NPCs, the effect of USP9X over-expression was analysed in embryonic stem cell (ESC)-derived NPCs. ESC lines were generated housing transgenes encoding USP9X under the transcriptional control of the human Nestin 2nd intron, and differentiated into neurons via NPC intermediates. The nestin-USP9X transgene expression resulted in two phenomena. First, it produced a dramatically altered cellular architecture wherein the majority (over 80%) of NPCs were arranged into ‘rosette’ colonies. These NPCs expressed markers of Radial Glial cells, named radial progenitors (RPs) thereafter, and were highly polarised akin to their in-vivo counterparts. Second, USP9X over expression caused a five-fold percentage increase of RPs and neurons. BrdU labelling, as well as the examination of the RP:neuron ratio indicated that nestin-USP9X enhanced the self-renewal of RPs but did not block their subsequent differentiation to neurons and astrocytes. nestin-USP9X RPs reformed rosette colonies following passage as single cells whereas control cells did not, suggesting it aids the establishment of polarity. From these data it was proposed that USP9X-induced polarisation of NPCs, provides an environment conducive for self-renewal. The nestin-USP9X transgene was subsequently used to generate transgenic embryos. Initially, three founding embryos were analysed. In two of three nestin-USP9X embryos, thickening, convolution, and disorganised CNS tissues were observed. A further four nestin- USP9X transgenic embryos generated through the breeding of a transgenic line revealed relatively milder defects of thickened CNS tissues. These effects are speculated to result from expansion of the NPC population, but await further experimental investigation. Together this study identifies USP9X as a regulator of NPC function. In-vivo, USP9X was found highly enriched in the apical end-feet structures, common to… Advisors/Committee Members: Wood, Stephen Andrew (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: neurogenesis; ubiquitin; embryonic stem cell

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Jolly, L. (2010). The deubiquitylating enzyme USP9X promotes the polarity and self-renewal of neural progenitor cells. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/65477

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Jolly, Lachlan. “The deubiquitylating enzyme USP9X promotes the polarity and self-renewal of neural progenitor cells.” 2010. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/65477.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Jolly, Lachlan. “The deubiquitylating enzyme USP9X promotes the polarity and self-renewal of neural progenitor cells.” 2010. Web. 22 Feb 2020.

Vancouver:

Jolly L. The deubiquitylating enzyme USP9X promotes the polarity and self-renewal of neural progenitor cells. [Internet] [Thesis]. University of Adelaide; 2010. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/65477.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Jolly L. The deubiquitylating enzyme USP9X promotes the polarity and self-renewal of neural progenitor cells. [Thesis]. University of Adelaide; 2010. Available from: http://hdl.handle.net/2440/65477

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

11. Bell, Francesca Y. Copper tolerance of Listeria monocytogenes strain DRDC8.

Degree: 2010, University of Adelaide

URL: http://hdl.handle.net/2440/65482

► Listeria monocytogenes is one of the most important food-borne pathogens due to the severity of the disease it can cause. While the virulence factors required… (more)

▼ Listeria monocytogenes is one of the most important food-borne pathogens due to the severity of the disease it can cause. While the virulence factors required for effective colonisation and infection of mammalian hosts have been well described, other genes may modulate disease persistence. For L. monocytogenes strain DRDC8, the ctpA gene encodes a copper transporting P-type ATPase that apparently maintains intra-cellular copper ion homeostasis (Francis & Thomas, 1997a) and is also required for persistent infection of the liver and spleens of mice (Francis & Thomas, 1997b). However, the distribution of this gene is apparently limited to non-clinically derived environmental L. monocytogenes isolates (Bell, 2002). This may be explained by carriage of ctpA on plasmid DNA (Bell, 2002). Based on predictions of function and proximity to the ctpA gene (pCT0020), ORFs pCT0017, pCT0018, pCT0019 and ctpA were identified as a putative a cop-like operon involved in copper ion transport in L. monocytogenes (Bell, 2002). Southern hybridisation analysis was used to confirm that the ctpA gene is carried on plasmid pCT100 in strain DRDC8. In addition, evidence to suggest that ctpA was encoded by bacteriophage DNA was not obtained. Furthermore, sequence analysis of DNA flanking ctpA identified ORFs that encode polypeptide sequences similar to proteins involved in plasmid replication and other plasmid-associated functions. Mating experiments provided evidence to show that plasmid pCT100 is not conjugative. This suggested that lateral transfer of this plasmid between cohabitating organisms may be limited. Sequence analysis of a 37.279 kbp region of plasmid pCT100 from L. monocytogenes strain DRDC8 (GenBank Accession U15554) showed this plasmid had regions of gene content and organisation similar to that of other characterised Listeria plasmids, particularly plasmid pLI100 from L. innocua CLIP11262 and plasmid pLM80 from L. monocytogenes strain 4b H7858. Gene’s common to these plasmids included those implicated in plasmid DNA replication, DNA transposition/insertion and heavy metal (cadmium) transport. Sequence analysis of plasmid pCT100 also identified regions of DNA absent from other Listeria sequences. For example, a DNA region encoding a series of polypeptide sequences similar to chromosomally-encoded proteins involved in copper transport in other Gram-positive bacteria was identified. The ORFs encoded by this region (pCT0017, pCT0018, pCT0019 and pCT0020 (ctpA), pCT0023, pCT0024, pCT0025, pCT0026, pCT0027) represent a novel cluster of genes implicated in copper homeostasis/tolerance that had not been previously described for other Listeria spp. PCR analysis was used to show that carriage of this copper gene cluster may be restricted to only some Australian ctpA positive L. monocytogenes isolates, typically of dairy and poultry origin. In addition to these plasmid-encoded ORFs, PCR and sequence analysis identified a chromosomal ORF (cutR) also implicated in copper homeostasis/tolerance for strain DRDC8. cutR encodes a polypeptide… Advisors/Committee Members: Thomas, Connor Jocelyn (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: Listeria; DRDC8; copper tolerance; P-type ATPase; ctpA; CopY-like; copper responsive regulator

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bell, F. Y. (2010). Copper tolerance of Listeria monocytogenes strain DRDC8. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/65482

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bell, Francesca Y. “Copper tolerance of Listeria monocytogenes strain DRDC8.” 2010. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/65482.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bell, Francesca Y. “Copper tolerance of Listeria monocytogenes strain DRDC8.” 2010. Web. 22 Feb 2020.

Vancouver:

Bell FY. Copper tolerance of Listeria monocytogenes strain DRDC8. [Internet] [Thesis]. University of Adelaide; 2010. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/65482.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bell FY. Copper tolerance of Listeria monocytogenes strain DRDC8. [Thesis]. University of Adelaide; 2010. Available from: http://hdl.handle.net/2440/65482

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

12. Papadopoulos, Magdalene. Characterisation of Shigella flexneri polysaccharide co-polymerase (PCP) protein Wzz: analysis of structure, function and protein interaction.

Degree: 2011, University of Adelaide

URL: http://hdl.handle.net/2440/65630

► In Shigella flexneri, Wzz[subscript]SF determines the lipopolysaccharides (LPS) O antigen (Oag) modal chain length of 11-17 repeat units (RUs). Wzz[subscript]SF has two transmembrane regions, the… (more)

▼ In Shigella flexneri, Wzz[subscript]SF determines the lipopolysaccharides (LPS) O antigen (Oag) modal chain length of 11-17 repeat units (RUs). Wzz[subscript]SF has two transmembrane regions, the N-terminal TM1 and the C-terminal TM2, and previous studies have shown that the TM2 region is important in Wzz function. The mechanism of Oag modal chain length regulation has not been revealed. Previous studies have probed the structure-function relationship of Wzz[subscript]SF and have suggested that function is a result of the overall structure and not one particular region. Genetic evidence suggests that Wzz may form a complex with other Oag processing proteins, possibly with the Wzy polymerase. This thesis describes in-frame linker mutagenesis of Wzz[subscript]SF, and five classes of Wzz insertion (Wzz[subscript]i) mutants with 5 amino acid insertions were identified: Class I (non-functional), Class II (conferred very short (VS) Oag chain length, 2-10 RUs), Class III (8-14 RUs), Class IV (11-19 RUs), and Class V (16-25 RUs). The susceptibility of strains expressing Wzzi mutants to colicin E2 was investigated, and a correlation between random/VS LPS Oag modal chain length, and susceptibility to colicin E2 was found. Chemical cross-linking analyses were conducted to assess Wzz oligomerisation and showed that high molecular weight proteins were easily detected in wild-type Wzz[subscript]SF and mutants from Classes V, but not easily detected in Classes II and III, and only Wzz[subscript]SF, Wzz[subscript]i Class IV and Class V dimers were detected after heating to 100ºC and in the presence of SDS, suggesting wild-type/longer LPS Oag modal chain length may be dependent on dimer stability. The involvement of the TM2 region in Wzz:Wzz interactions was also investigated. S. typhimurium Wzz (Wzz[subscript]ST) confers an LPS Oag modal chain length of Long-type (L-type) 19-30 RUs, and Wzz[subscript]ST and Wzz[subscript]SF have identical residues in the conserved residues of their TM2 regions. Wzz[subscript]ST expression in Wzz deficient S. flexneri strain confers an L-type LPS Oag modal chain length, however co-expression of Wzz[subscript]ST with Wzz[subscript]SF resulted in mono-modal LPS Oag modal chain length. A previously constructed Wzz mutant which had two G305A/G311A substitutions in the TM2 region confers a VS LPS Oag modal chain length (3-8 RUs), however co-expression of Wzz[subscript]G305A/G311A with wild-type Wzz[subscript]SF resulted in LPS with a bimodal Oag chain length distribution (both wild-type 11-17 RUs, and VS-type 3-8 RUs). Strains expressing His[subscript]6-Wzz[subscript]SF and FLAG-tagged version of Wzz[subscript]ST, Wzz[subscript]SF and Wzz[subscript]G305A/G311A were used in co-purification assays. Purified His[subscript]6-Wzz[subscript]SF and had FLAGWzz[subscript]ST was in the eluted fraction, demonstrating that FLAG-Wzz[subscript]ST interacted with His[subscript]6-Wzz[subscript]SF. However when His[subscript]6-Wzz[subscript]SF was purified from a strain co-expressing FLAGWzz[subscript]G305A/G311A,… Advisors/Committee Members: Morona, Renato (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: PCP; O antigen; WZZ; polysaccaride

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Papadopoulos, M. (2011). Characterisation of Shigella flexneri polysaccharide co-polymerase (PCP) protein Wzz: analysis of structure, function and protein interaction. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/65630

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Papadopoulos, Magdalene. “Characterisation of Shigella flexneri polysaccharide co-polymerase (PCP) protein Wzz: analysis of structure, function and protein interaction.” 2011. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/65630.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Papadopoulos, Magdalene. “Characterisation of Shigella flexneri polysaccharide co-polymerase (PCP) protein Wzz: analysis of structure, function and protein interaction.” 2011. Web. 22 Feb 2020.

Vancouver:

Papadopoulos M. Characterisation of Shigella flexneri polysaccharide co-polymerase (PCP) protein Wzz: analysis of structure, function and protein interaction. [Internet] [Thesis]. University of Adelaide; 2011. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/65630.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Papadopoulos M. Characterisation of Shigella flexneri polysaccharide co-polymerase (PCP) protein Wzz: analysis of structure, function and protein interaction. [Thesis]. University of Adelaide; 2011. Available from: http://hdl.handle.net/2440/65630

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

13. Denton, Jai Andrew. From model organism to industrial workhorse: analysis of genes in Aspergillus nidulans and disruption of cre2 for Trichoderma reesei strain improvement.

Degree: 2011, University of Adelaide

URL: http://hdl.handle.net/2440/67239

► Carbon catabolite repression is a regulatory system whereby an organism can sequentially utilise carbon sources based on their available energy. This system results in the… (more)

▼ Carbon catabolite repression is a regulatory system whereby an organism can sequentially utilise carbon sources based on their available energy. This system results in the repression of genes encoding enzymes responsible for the utilisation of poorer carbon sources when preferable ones are available. Carbon catabolite repression has been extensively studied in the filamentous fungus Aspergillus nidulans. Repression is mediated via CreA, a zinc finger DNA binding protein, which is in turn, either directly or indirectly, regulated by an ubiquitination / deubiquitination system involving CreB, CreC and CreD. Previous work demonstrated that the A. nidulans genome contains a CreD homologue, ApyA, and that both of these proteins interact with an ubiquitin ligase, HulA. This relationship was proposed to be similar to Rod1p and Rog3p and their interaction with the ubiquitin ligase Rsp5p in Saccharomyces cerevisiae. Both apyA and hulA were targeted for disruption to facilitate phenotypic analysis and the study of epistatic interactions. Deletion of hulA was shown to be lethal in an A. nidulans haploid, but viable as a heterozygote in an A. nidulans diploid. The only detectable phenotypes of this deletion in a heterozygous diploid were increased sensitivity to molybdate and acriflavine. A strain containing a disruption of apyA did not demonstrate any detectable phenotypes, however, the apyA disruption allele showed epistatic interactions with mutations in creB, creC and creD. The disruption of apyA partially suppressed the phenotype of sensitivity to allyl alcohol in the presence of glucose displayed by strains containing mutations in creB and creC. However, the level of suppression exhibited by the disruption of apyA was not as strong as that shown by the creD34 mutation. A strain containing mutations in both creD and apyA demonstrated severe morphological deficiencies on minimal media as well as stronger resistance to acriflavine than creD34 alone, and resistance to molybdate. Bioinformatic analysis of CreD and CreD‐like proteins, including ApyA, from sequenced members of the Aspergilli and Rod1p, Rog3p and related proteins from members of Saccharomycetes suggested that the arrestin-like proteins, a group to which these belong, are subject to frequent gene duplication events. The number and range of sequenced fungal genomes also allowed a bioinformatic examination of the conservation of proteins involved in the carbon repression mechanisms across the fungal kingdom. A homologue of CreA was identified only within the members of Ascomycota that were examined, but putative homologues of CreB and CreC were identified across the fungal kingdom. The Saccharomycetes were an exception to this as a CreC homologue was not indentified and the CreB homologue was highly divergent or absent. The filamentous fungus, Trichoderma reesei is an important source of cellulases for use in the textile and alternative fuel industries. Previous studies have suggested a benefit for the manipulation of carbon catabolite repression for strain… Advisors/Committee Members: Kelly, Joan Maree (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: genetics; filamentous fungi; gene regulation; biotechnology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Denton, J. A. (2011). From model organism to industrial workhorse: analysis of genes in Aspergillus nidulans and disruption of cre2 for Trichoderma reesei strain improvement. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/67239

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Denton, Jai Andrew. “From model organism to industrial workhorse: analysis of genes in Aspergillus nidulans and disruption of cre2 for Trichoderma reesei strain improvement.” 2011. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/67239.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Vancouver:

Denton JA. From model organism to industrial workhorse: analysis of genes in Aspergillus nidulans and disruption of cre2 for Trichoderma reesei strain improvement. [Internet] [Thesis]. University of Adelaide; 2011. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/67239.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Denton JA. From model organism to industrial workhorse: analysis of genes in Aspergillus nidulans and disruption of cre2 for Trichoderma reesei strain improvement. [Thesis]. University of Adelaide; 2011. Available from: http://hdl.handle.net/2440/67239

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

14. Knott, Michelle Louise. Host-parasite interactions in primary and secondary infections with Nippostrongylus brasiliensis and Heligmosomoides bakeri.

Degree: 2010, University of Adelaide

URL: http://hdl.handle.net/2440/67240

► Parasitic helminth infections are a significant problem worldwide. Some helminth species are becoming resistant to current therapies and new forms of treatment and/or vaccines are… (more)

▼ Parasitic helminth infections are a significant problem worldwide. Some helminth species are becoming resistant to current therapies and new forms of treatment and/or vaccines are required. Nippostrongylus brasiliensis is a tissue-invasive parasitic helminth that infects rodents, and the lifecycle of this parasite is similar to that of the human hookworms. The aims of this study were to investigate primary and secondary immune responses to N. brasiliensis, focusing on the pre-lung phase of infection. The roles of cytokines, chemokines, signalling pathways and leukocytes such as eosinophils were investigated in the skin, lungs and small intestine. The roles of eosinophils were also investigated in primary infections with the intestinal nematode Heligmosomoides bakeri. Interleukin (IL)-5 is important for eosinophil development and maturation and for protection during some helminth infections. Over-expression of IL-5 provides potent protection in primary infections with N. brasiliensis in the pre-lung phase of infections. Although mice deficient in IL-5 or eosinophils might therefore be predicted to be more susceptible to N. brasiliensis, IL-5-deficient (IL-5⁻/⁻) and eosinophil-deficient (ΔdblGATA) mice showed similar infection patterns as wildtype (WT) mice during primary N. brasiliensis infections. Intestinal worm and/or egg numbers however were elevated in mice with defective eosinophilopoiesis compared with WT animals. In secondary infections, despite skin inflammatory responses (4 hours p.i.) being similar in WT, IL-5⁻/⁻ and ΔdblGATA animals, at day 2 p.i., lung larval burdens in the two latter hosts were significantly higher than in the resistant WT controls. However, parasites were expelled from intestines of all mice by day 7 of secondary infections. These data suggest that in the pre-gut phase of secondary infection, IL-5 and eosinophils play an important role in resistance to N. brasiliensis. Despite this, eosinophils do not appear to be essential for protection mediated within the gut during secondary infections, even though IL-5 and eosinophils do appear to confer some protection in the gut during primary infections. Complement is required for the recruitment of eosinophils into the skin in the first 150 minutes of primary infection with N. brasiliensis (Giacomin et al., 2008a), however other chemotactic factors appear to be involved after this time. Although eotaxin is chemotactic for eosinophils in some tissues, the importance of eotaxin and signalling pathways involved in expression of this chemokine has not been previously characterized in N. brasiliensis infections. Signal transducer and activator of transcription (STAT)6 is a key transcription factor in the IL-4/IL-13 signalling pathway and these cytokines can induce expression of eotaxin in some tissues. Expulsion of N. brasiliensis adult worms during primary infections is profoundly impaired in STAT6- deficient (STAT6⁻/⁻) mice. IL-5 Tg mice are highly resistant to primary infections with N. brasiliensis and in the current study, it was shown that… Advisors/Committee Members: Dent, Lindsay Agin (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: IL-5; eosinophic parasite; helminth; primary and secondary infections; Nippostrongylus brasiliensis; Heligmosomoides bakeri; STAT6; IL-4Ra; IL-13; eotaxin; FVB/N mouse

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Knott, M. L. (2010). Host-parasite interactions in primary and secondary infections with Nippostrongylus brasiliensis and Heligmosomoides bakeri. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/67240

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Knott, Michelle Louise. “Host-parasite interactions in primary and secondary infections with Nippostrongylus brasiliensis and Heligmosomoides bakeri.” 2010. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/67240.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Knott, Michelle Louise. “Host-parasite interactions in primary and secondary infections with Nippostrongylus brasiliensis and Heligmosomoides bakeri.” 2010. Web. 22 Feb 2020.

Vancouver:

Knott ML. Host-parasite interactions in primary and secondary infections with Nippostrongylus brasiliensis and Heligmosomoides bakeri. [Internet] [Thesis]. University of Adelaide; 2010. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/67240.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Knott ML. Host-parasite interactions in primary and secondary infections with Nippostrongylus brasiliensis and Heligmosomoides bakeri. [Thesis]. University of Adelaide; 2010. Available from: http://hdl.handle.net/2440/67240

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

15. Belle, Leila. Tyrosine phosphatase pez: a novel regulator of TGFβ signalling, epithelial-mesenchymal transition and protein secretion in development and cancer.

Degree: 2011, University of Adelaide

URL: http://hdl.handle.net/2440/69633

► The body of work documented in this thesis defines the protein tyrosine phosphatase Pez as a novel positive regulator of TGFβ signalling, epithelialmesenchymal transition and… (more)

▼ The body of work documented in this thesis defines the protein tyrosine phosphatase Pez as a novel positive regulator of TGFβ signalling, epithelialmesenchymal transition and protein secretion. In a zebrafish model of embryonic development, Pez was found to be expressed transiently in discrete, tissue-specific regions of the developing brain, heart, pharyngeal arches and somites, and knock-down of Pez expression was found to result in architectural defects in these organs, indicating a crucial role for Pez in organogenesis during embryonic development. Over-expression of Pez in epithelial MDCK cells induced an epithelial-mesenchymal transitio (EMT), as confirmed by increased expression of mesenchymal genes and EMT-associated transcription factors, concomitant with a reduction in epithelial gene expression and transition from epithelial to mesenchymal-like morphology. Pez-dependent induction of EMT was found to be a consequence of increased TGFβ signalling in Pez-expressing cells in this in vitro model. Furthermore, TGFβ₃ mRNA was found to be co-expressed with Pez in a number of tissues during zebrafish development, and TGFB₃ expression was lost from these tissues following Pez knock-down, suggesting that Pez is required for TGFB₃ expression in these tissues. Pez-dependent regulation of TGFβ was also found to occur in the setting of human breast cancers, with manipulation of Pez expression altering TGFB secretion in human breast cancer-derived cell lines. Additionally, altered Pez expression led to widespread changes in the secretome of these breast cancer cell lines. In breast and other epithelial cell types, Pez was found to localise predominantly to a perinuclear region that partially co-localised with markers of the golgi apparatus. Preliminary investigations suggest that Pez-dependent activation of golgi-localised Src family kinases may contribute to its effects in regulating protein secretion. Together, these results implicate Pez as a novel regulator of embryonic development, TGFβ production and EMT, and a modulator of the tumour cell secretome. Further investigation into the molecular mechanism by which Pez mediates these effects has the potential to enhance our understanding of essential biological processes contributing to embryonic development, tissue homeostasis, and human disease states, including cancer. Advisors/Committee Members: Khew-Goodall, Yeesim (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: phosphatase; TGFβ; EMT; development; cancer; zebrafish; secretion; golgi; Pez; PTPN14

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Belle, L. (2011). Tyrosine phosphatase pez: a novel regulator of TGFβ signalling, epithelial-mesenchymal transition and protein secretion in development and cancer. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/69633

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Belle, Leila. “Tyrosine phosphatase pez: a novel regulator of TGFβ signalling, epithelial-mesenchymal transition and protein secretion in development and cancer.” 2011. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/69633.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Belle, Leila. “Tyrosine phosphatase pez: a novel regulator of TGFβ signalling, epithelial-mesenchymal transition and protein secretion in development and cancer.” 2011. Web. 22 Feb 2020.

Vancouver:

Belle L. Tyrosine phosphatase pez: a novel regulator of TGFβ signalling, epithelial-mesenchymal transition and protein secretion in development and cancer. [Internet] [Thesis]. University of Adelaide; 2011. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/69633.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Belle L. Tyrosine phosphatase pez: a novel regulator of TGFβ signalling, epithelial-mesenchymal transition and protein secretion in development and cancer. [Thesis]. University of Adelaide; 2011. Available from: http://hdl.handle.net/2440/69633

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

16. Sugano, Yuya. Characterization of the zebrafish orthologue of Klotho.

Degree: 2011, University of Adelaide

URL: http://hdl.handle.net/2440/70207

► Klotho is a multi-functional anti-ageing protein. Its deletion causes accelerated ageing in mice while its overexpression increases mouse longevity. Klotho is a single pass transmembrane… (more)

▼ Klotho is a multi-functional anti-ageing protein. Its deletion causes accelerated ageing in mice while its overexpression increases mouse longevity. Klotho is a single pass transmembrane protein and its extracellular domain is cleaved at the cell surface by proteolytic enzymes and subsequently shed into the blood and cerebrospinal fluid, thereby functioning as a humoral factor. The transmembrane form of Klotho is a co-receptor for fibroblast growth factor 23 (Fgf23). Fgf23 acts on the kidney to induce phosphate excretion into urine. However, in the absence of Klotho, Fgf23 cannot bind to its receptor. Therefore, Klotho deficient mice show hyperphosphataemia. The extracellular domain of Klotho released by proteolytic cleavage inhibits the insulin/insulin-like signaling pathway. The inhibition of the insulin pathway enhances protection of cells from oxidative stress and this is an evolutionarily conserved mechanism for extending life span. In addition to this function, secreted Klotho is known to activate calcium ion channels and inhibit the Wnt pathway. Taken together, Klotho acts as an ageing suppressor, but the precise mechanism of how Klotho exerts these functions is not fully understood. In particular, the function of Klotho against oxidative stress needs to be closely investigated as oxidative stress is a major contributor to ageing as well as many diseases associated with ageing, such as Alzheimer’s disease. The strength of zebrafish as a model system for human diseases has been displayed over the past two decades. Zebrafish possess relative simplicity of organ structure while preserving morphological and genetical similarity to higher vertebrates. In this study, I characterize the zebrafish orthologue of Klotho. Chapter 2 (thesis chapter in the form of a manuscript) describes the identification of the candidate gene and confirmation of its orthologous relationship with Klotho genes in other organisms by bioinformatics approaches. It determines the temporal expression of klotho during embryonic development and the tissue specificity of its expression in adult zebrafish by RT-PCR. It also investigates the relative levels of klotho mRNA transcript in zebrafish embryos and adult tissues by quantitative real time RT-PCR. Chapter 3 describes exploration of expression of zebrafish Klotho in response to oxidative stress using an oxidative stress inducer, hydrogen peroxide. It also examines proteolytic cleavage of zebrafish Klotho as seen in humans and mice by Western Blotting analysis. Chapter 4 describes an attempt to create site-directed mutations in the klotho coding sequence in the genome of zebrafish using zinc finger nucleases. Advisors/Committee Members: Lardelli, Michael Trent (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: Klotho; zebrafish; RT-PCR; quantitative real-time; PCR; in situ hybridization; oxidative stress; western blotting; zinc finger nucleases

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sugano, Y. (2011). Characterization of the zebrafish orthologue of Klotho. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/70207

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sugano, Yuya. “Characterization of the zebrafish orthologue of Klotho.” 2011. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/70207.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sugano, Yuya. “Characterization of the zebrafish orthologue of Klotho.” 2011. Web. 22 Feb 2020.

Vancouver:

Sugano Y. Characterization of the zebrafish orthologue of Klotho. [Internet] [Thesis]. University of Adelaide; 2011. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/70207.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sugano Y. Characterization of the zebrafish orthologue of Klotho. [Thesis]. University of Adelaide; 2011. Available from: http://hdl.handle.net/2440/70207

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

17. McCartney, Erin. Molecular interactions between alcohol, hepatitis C virus and interferon.

Degree: 2011, University of Adelaide

URL: http://hdl.handle.net/2440/70235

► Hepatitis C virus (HCV) is a significant human pathogen that in many cases, establishes a chronic life long infection of the liver, resulting in progressive… (more)

▼ Hepatitis C virus (HCV) is a significant human pathogen that in many cases, establishes a chronic life long infection of the liver, resulting in progressive liver disease that culminates in the development of cirrhosis and hepatocellular carcinoma (HCC). The only treatment option available for HCV infection is a combination therapy of Interferon-α (IFN-α) and Ribavirin. However, it is only successful in a limited number of patients. There are a number of co-factors that accelerate liver disease in chronic hepatitis C (CHC) and one of the most significant factors is alcohol consumption. Furthermore, alcohol consumption has been shown to reduce the efficacy of IFN-α treatment. Despite these clinical observations, the molecular mechanisms by which alcohol exerts these effects are unknown and remain relatively unexplored. This is largely due to the lack of an appropriate model system to enable studies into the interaction between the HCV life cycle, alcohol metabolism and IFN. To overcome this limitation, we have developed an in vitro cell culture model system that enables Huh-7 cells to metabolise alcohol (ethanol), via the enzyme cytochrome P4502E1 (CYP2E1), while also supporting HCV replication directed from both the HCV replicon and infectious HCV model systems. As such, this model system has been used in this thesis to extensively investigate the interactions between alcohol metabolism, HCV and IFN. It is known clinically that HCV infected persons who consume alcohol, have exacerbated liver disease and in some cases increased serum of HCV. One postulated mechanism for this effect is that alcohol consumption increases HCV replication, which in turn leads to increased viral burden in the liver and associated pathogenic effects. We have shown that CYP2E1 mediated metabolism of alcohol increases HCV RNA replication in vitro, in both the replicon and infectious HCV model systems. Furthermore, we have demonstrated that this process is mediated via the oxidative stress produced by alcohol metabolism, as the anti-oxidant NAC blocked this alcoholinduced increase in HCV RNA replication. These observations correlate with what is noted clinically and suggest a potential mechanism whereby alcohol consumption in chronically infected HCV individuals, leads to accelerated rates of liver disease progression. These findings form a rationale to clinically investigate the use of antioxidant therapy in CHC patients consuming alcohol. In this thesis we present a molecular mechanism for the reduced response rates to IFN-α therapy in HCV infected individuals consuming alcohol. Specifically we have shown that alcohol metabolism attenuates the anti-HCV activity of IFN-α via perturbation of the JAK/STAT signaling cascade and subsequently decreases the expression of anti-viral ISGs, which are the effector molecules of an IFN response. Thus alcohol metabolism seems to be able to blunt the anti-viral effects of IFN and this has implications for anti-viral directed therapy and the innate immune response to HCV infection in the liver. Also arising… Advisors/Committee Members: Beard, Michael Robert (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: alcohol; ethanol; hepatitis C virus; interferon; STAT3; STAT1

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

McCartney, E. (2011). Molecular interactions between alcohol, hepatitis C virus and interferon. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/70235

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

McCartney, Erin. “Molecular interactions between alcohol, hepatitis C virus and interferon.” 2011. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/70235.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

McCartney, Erin. “Molecular interactions between alcohol, hepatitis C virus and interferon.” 2011. Web. 22 Feb 2020.

Vancouver:

McCartney E. Molecular interactions between alcohol, hepatitis C virus and interferon. [Internet] [Thesis]. University of Adelaide; 2011. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/70235.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

McCartney E. Molecular interactions between alcohol, hepatitis C virus and interferon. [Thesis]. University of Adelaide; 2011. Available from: http://hdl.handle.net/2440/70235

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

18. McCarthy, Peter James. Investigation into the molecular function of the neuronal Hu RNA binding protein, HuCsv1.

Degree: 2011, University of Adelaide

URL: http://hdl.handle.net/2440/70239

► Of the four Hu genes found in most vertebrates (HuA, HuB, HuC and HuD), all except HuA exhibit mRNA and protein expression that is essentially… (more)

▼ Of the four Hu genes found in most vertebrates (HuA, HuB, HuC and HuD), all except HuA exhibit mRNA and protein expression that is essentially restricted to post-mitotic neurons of the developing and adult nervous systems. Spatial and temporal examination of individual “neuronal Hu” (nHu = HuB, HuC and HuD) proteins in brain tissue suggests nHu proteins may play a functional role during neuronal differentiation; as RNA-binding proteins, the nHu proteins may participate in gene regulatory events that are essential for acquisition of the neuronal phenotype. We have identified a number of candidate mRNA targets of the nHu proteins. Our data suggest that the majority of these mRNAs interact with nHu proteins through sequences present in their 3´ untranslated regions (UTRs). From this 3´UTR target subset, several mRNAs were selected for further examination based on reported roles for their encoded proteins during axonogenesis, a critical developmental process during which nascent neurons grow and extend axons that eventually connect to and form synaptic connections with other neurons. The mRNAs chosen encode for cytoskeleton-modifying proteins; Cofilin, Vasodilator-Stimulated Phosphoprotein (VASP) and the Rho GTPase Cdc42. The primary aim of the work reported in this thesis was to characterise the effect of interactions between the neuronal Hu protein HuC, and the CLIP-identified 3´UTRs listed above. To do this, the 3´UTR sequences were cloned into reporter vectors (both fluorescent and luciferase reporter-based) to produce reporter protein-encoding messages that included a putative target 3´UTR. These vectors were then used in co-transfection experiments with or without HuC and measurements of reporter protein and mRNA abundance obtained. Interestingly, despite initial speculation that HuC might be involved in directly regulating protein expression from target mRNAs, no significant effect of HuC on protein production from any of the 3´UTR-reporter mRNAs tested was observed. However and quite unexpectedly, measurement of 3´UTR-reporter mRNA abundance from co-transfection assays revealed a potential role for HuC in modulating alternative polyadenylation site choice for one of the CLIP-identified 3´UTR sequences. Regulation of mRNA polyadenylation site choice may be a novel mechanism by which nHu proteins post-transcriptionally control gene expression during neuronal development. Advisors/Committee Members: Jensen, Kirk Blomquist (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: post-transcriptional gene regulation; RNA binding proteins; polyadenylation; aternative splicing; neuronal development

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

McCarthy, P. J. (2011). Investigation into the molecular function of the neuronal Hu RNA binding protein, HuCsv1. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/70239

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

McCarthy, Peter James. “Investigation into the molecular function of the neuronal Hu RNA binding protein, HuCsv1.” 2011. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/70239.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

McCarthy, Peter James. “Investigation into the molecular function of the neuronal Hu RNA binding protein, HuCsv1.” 2011. Web. 22 Feb 2020.

Vancouver:

McCarthy PJ. Investigation into the molecular function of the neuronal Hu RNA binding protein, HuCsv1. [Internet] [Thesis]. University of Adelaide; 2011. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/70239.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

McCarthy PJ. Investigation into the molecular function of the neuronal Hu RNA binding protein, HuCsv1. [Thesis]. University of Adelaide; 2011. Available from: http://hdl.handle.net/2440/70239

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

19. Lloyd, Andrew Henry Mark. The origin and characterisation of new nuclear genes originating from a cytoplasmic organellar genome.

Degree: 2011, University of Adelaide

URL: http://hdl.handle.net/2440/70280

► Endosymbiotic transfer of DNA and functional genes from the cytoplasmic organelles (mitochondria and chloroplasts) to the nucleus has been a major factor driving the origin… (more)

▼ Endosymbiotic transfer of DNA and functional genes from the cytoplasmic organelles (mitochondria and chloroplasts) to the nucleus has been a major factor driving the origin of new nuclear genes, a process central to eukaryote evolution. Recent developments have allowed the experimental reconstruction of DNA transfer and functional gene transfer, enabling investigation of the molecular mechanisms involved in these important evolutionary processes. To simulate the process of functional endosymbiotic gene transfer, a chloroplast reporter gene aadA, which had been transferred from the chloroplast to the nucleus, was monitored for nuclear activation. In total 16 plant lines were screened, each line representing an independent nuclear insertion of the aadA gene. For each line ~50 million cells were screened resulting in three plants being recovered in which aadA showed strong nuclear activation. Activation occurred by acquisition of the CaMV 35S nuclear promoter or by nuclear activation of the native chloroplast promoter. Two fortuitous sites resident within the 3' UTR of aadA mRNA both promoted polyadenylation without any sequence change. In addition, cryptic nuclear activity of the chloroplast promoter was revealed which became conspicuous when present in multiple nuclear copies. To determine the method of chloroplast DNA insertion into the nucleus the insertion site was sequenced in line kr2.2. Complete characterisation of the nuclear sequence before and after gene transfer demonstrated simultaneous insertion of multiple chloroplast DNA fragments via synthesis dependent non-homologous end joining, probably at a site of double strand break (DSB) repair. To further investigate the role of DSB repair in the nuclear insertion of organelle DNA, DSBs were induced at a specific nuclear location using the rare-cutting endonuclease I-SceI and the resulting repair events were observed. Analysis of ~300 DSB repair events indicated that most involved the loss of nucleotides from one or both ends being joined. Insertions were observed in five repair events. None of the inserted sequences were of organelle origin. Notably, the amount of nuclear sequence deleted was significantly larger in repair events involving insertion than in those without insertion, indicating that the two types of repair may be mediated by distinct pathways. Advisors/Committee Members: Timmis, Jeremy Newman (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: chloroplast; endosymbiosis; evolution; gene transfer; tobacco

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lloyd, A. H. M. (2011). The origin and characterisation of new nuclear genes originating from a cytoplasmic organellar genome. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/70280

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lloyd, Andrew Henry Mark. “The origin and characterisation of new nuclear genes originating from a cytoplasmic organellar genome.” 2011. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/70280.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lloyd, Andrew Henry Mark. “The origin and characterisation of new nuclear genes originating from a cytoplasmic organellar genome.” 2011. Web. 22 Feb 2020.

Vancouver:

Lloyd AHM. The origin and characterisation of new nuclear genes originating from a cytoplasmic organellar genome. [Internet] [Thesis]. University of Adelaide; 2011. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/70280.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lloyd AHM. The origin and characterisation of new nuclear genes originating from a cytoplasmic organellar genome. [Thesis]. University of Adelaide; 2011. Available from: http://hdl.handle.net/2440/70280

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

20. Wiszniak, Sophie. Investigating mechanisms of post-transcriptional gene regulation in the germ cells of Zebrafish.

Degree: 2011, University of Adelaide

URL: http://hdl.handle.net/2440/70450

► In most organisms, the primordial germ cells are specified and set aside from the surrounding somatic tissues very early in development. Their ability to carry… (more)

▼ In most organisms, the primordial germ cells are specified and set aside from the surrounding somatic tissues very early in development. Their ability to carry out a gene regulatory program quite distinct from the surrounding somatic cells, and their capacity to specify entire new organisms has made them a focus of many studies that seek to understand how specific transcriptional and translational programs contribute to cell fate. Zebrafish, a vertebrate with external development of the embryo, is currently one of the best animal models for understanding the molecular basis of germ cell specification. Briefly, germ cell specification is dependent on maternally provided cytoplasmic determinants, termed the germ plasm. The germ plasm, is localised to areas of the embryo that will become the germ cells later in development by inheritance the germ plasm through cleavage divisions. A number of mRNA components of the germ plasm have been identified; interestingly many of them encode RNA-binding proteins, and almost all of them have invertebrate and mammalian orthologues. Evidence suggests that these maternally provided mRNA determinants are specifically maintained in the germ cells throughout embryonic development, and at least some of these gene products are essential for germ cell specification. A number of studies have begun to elucidate the molecular mechanisms that allow germ cell specific maintenance of these mRNAs, and also to identify how maternally provided messages destined for the germ cells are destabilised and eliminated in the somatic tissues. For example, the germ cell specific mRNAs nanos and TDRD7 are destabilised in somatic cells through interactions of the 3´UTR sequences with the microRNA miR-430. This miR-430-mediated repression is overcome in germ cells through the binding of an RNA-binding protein Dead end (DND) to distinct sites within the nanos and TDRD7 3´UTRs. This thesis details a study of the zebrafish orthologue of HuB, a highly conserved RNAbinding protein with expression in neurons, testes and ovaries in adult vertebrates. In zebrafish, HuB mRNA is maternally provided, and is restricted to the germ cells by 24 hours of development; this is the first report to indicate expression of HuB in the germ cells of vertebrates, suggesting a possible role for HuB in germ cell development. Through detailed mutagenesis studies, the HuB 3´UTR has been found to contain a set of four destabilising elements, which bring about somatic degradation of the mRNA, and a separate, 30-nucleotide motif that is responsible for germ cell specific stabilisation of the message. None of these identified destabilising elements are targets for miR-430, and thus they represent novel sequence elements for somatic message degradation in zebrafish. Through a candidate screening approach, DAZL, a germ cell specific RNA-binding protein, was identified as being capable of stabilising HuB mRNA. Further-more, DAZL was shown to mediate this stabilisation of HuB mRNA by interacting, either directly or indirectly, with the… Advisors/Committee Members: Jensen, Kirk Blomquist (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: zebrafish; germ cells; RNA; 3'UTR; HuB; DAZL

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wiszniak, S. (2011). Investigating mechanisms of post-transcriptional gene regulation in the germ cells of Zebrafish. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/70450

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wiszniak, Sophie. “Investigating mechanisms of post-transcriptional gene regulation in the germ cells of Zebrafish.” 2011. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/70450.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wiszniak, Sophie. “Investigating mechanisms of post-transcriptional gene regulation in the germ cells of Zebrafish.” 2011. Web. 22 Feb 2020.

Vancouver:

Wiszniak S. Investigating mechanisms of post-transcriptional gene regulation in the germ cells of Zebrafish. [Internet] [Thesis]. University of Adelaide; 2011. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/70450.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wiszniak S. Investigating mechanisms of post-transcriptional gene regulation in the germ cells of Zebrafish. [Thesis]. University of Adelaide; 2011. Available from: http://hdl.handle.net/2440/70450

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

21. Wells, Simon J. An investigation into the development and patterning of dorsal longitudinal ascending interneurons in Danio rerio.

Degree: 2011, University of Adelaide

URL: http://hdl.handle.net/2440/71720

► The dorsal longitudinal ascending (DoLA) interneurons are an uncommon, seemingly irregularly distributed interneuron type of the developing embryonic zebrafish spinal cord. For reasons not yet… (more)

▼ The dorsal longitudinal ascending (DoLA) interneurons are an uncommon, seemingly irregularly distributed interneuron type of the developing embryonic zebrafish spinal cord. For reasons not yet understood DoLA interneurons express tbx16, a T-box transcription factor originally recognised for its important role in mesodermal development. This is the only cell type expressing tbx16 in the developing spinal cord, making DoLA neurons one of the few neuronal types that can be identified by expression of a unique molecular marker. Throughout the natural world regularity in pattern formation is frequent; mechanisms that direct the production of regular patterns have been studied and many are well understood. The creation of irregular "patterns", especially in embryo development has been subjected to far less analysis. This is largely because studies in developmental biology frequently involve methods that disrupt regular patterning while the disruption of an irregular pattern is likely to result in similarly irregular pattern. The DoLA interneurons with their unique genetic marker offer a rare opportunity to investigate the mechanisms behind irregular patterns in development. This is of particular importance in the development of the spinal cord, as most of the known vertebrate spinal interneurons appear to have irregular distributions. The main focus of the research presented in this thesis has been to try to understand how the distribution pattern of DoLA interneurons is generated. This knowledge may then be extended to other spinal neurons and possibly to other irregular developmental patterns. In the work described in this thesis the distribution of DoLA interneurons has been extensively examined statistically. It was found that there is an underlying cryptic organisation to their peculiar distribution. This led to the surprising discovery that these neurons migrate rostrally a significant distance along the spinal cord. These neurons were also found in larval zebrafish at much older times than has previously been described, suggesting that they may play a role in post-embryonic stages. Notch signalling appears to have an influence on DoLA interneuron distribution since perturbing Presenilin (Psen) function affects the number of these cells. Interestingly, DoLA cell number is not affected when Psen1 function is inhibited but increases when Psen2 function is inhibited. Furthermore the wild type level of DoLA interneuron number can be partially rescued by inhibiting Psen1 function in combination with inhibition of Psen2 function. The creation of transgenic zebrafish lines where GFP is transcribed from tbx16 promoter sequence is described. These animals were produced to attempt to discover more about the patterning of DoLA interneurons and the function of tbx16 during development. Serendipitously, one of these transgenic lines expresses GFP in the commissural primary ascending (CoPA) interneurons. This led to the discovery that the CoPA interneurons are marked by mafba/valentino, revealing a new unique spinal neuron… Advisors/Committee Members: Lardelli, Michael Trent (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: rostrocaudal patterning; dola interneurons; spinal cord; dorsal longitudinal ascending; danio rerio; tbx16; spadetail; migration; uncaging

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APA (6^th Edition):

Wells, S. J. (2011). An investigation into the development and patterning of dorsal longitudinal ascending interneurons in Danio rerio. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/71720

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wells, Simon J. “An investigation into the development and patterning of dorsal longitudinal ascending interneurons in Danio rerio.” 2011. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/71720.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wells, Simon J. “An investigation into the development and patterning of dorsal longitudinal ascending interneurons in Danio rerio.” 2011. Web. 22 Feb 2020.

Vancouver:

Wells SJ. An investigation into the development and patterning of dorsal longitudinal ascending interneurons in Danio rerio. [Internet] [Thesis]. University of Adelaide; 2011. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/71720.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wells SJ. An investigation into the development and patterning of dorsal longitudinal ascending interneurons in Danio rerio. [Thesis]. University of Adelaide; 2011. Available from: http://hdl.handle.net/2440/71720

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

22. Moussavi Nik, Seyyed Hani. Molecular responses to low oxygen levels/oxidative stress in zebrafish.

Degree: 2011, University of Adelaide

URL: http://hdl.handle.net/2440/72269

► Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with pathologies such as neuron loss, glial cell proliferation, extracellular deposition of senile plaques from the accumulation… (more)

▼ Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with pathologies such as neuron loss, glial cell proliferation, extracellular deposition of senile plaques from the accumulation of amyloid beta (Aβ) peptides and deposition of intracellular neurofibrillary tangles. Aβ is created from the cleavage of the Amyloid Precursor Protein (APP) by two different types of aspartyl proteases, β- and γ-secretase. The majority of AD cases are sporadic and have a late onset.Mutations in the genes encoding APP, PRESENILIN1 and 2 (PSEN1 and PSEN2) genes cause an autosomal dominant inherited form of the disease with an early onset known as familial AD. In some sporadic cases an aberrant splice variant of PSEN2named PS2V is formed that can be found in inclusion bodies in the brain. PS2V results from the binding of the High Mobility Group A1a (HMGA1a) protein close to the splice donor site of exon 5 of PSEN2. The High Mobility Group A1 protein,HMGA1, is widely expressed during embryo development but not in adults. Its expression can be induced in adult neurons by hypoxia/oxidative stress and it is commonly reactivated in many types of cancer. Hypoxia can be a direct consequence of hypoperfusion, a common vascular component among Alzheimer’s disease risk factors and may play an important role in AD pathogenesis. BETA-SITE AMYLOID BETA A4 PRECURSOR PROTEIN-CLEAVING ENZYME 1, BACE1 is responsible, with γ-secretase, for cleavage of AMYLOID PRECURSOR PROTEIN, APP to produce Aβ peptide. A recent study observed that oxidative stress upregulates BACE1 expression via a regulatory pathway that is dependent on γ-secretase cleavage of APP and that results in increased Aβ peptide production. In this thesis, we define strategies for exposure of zebrafish to hypoxia and “chemical hypoxia”. We identifiyendogenous zebrafish hmga1 in an attempt to investigate PS2V formation in fish. We also demonstrate that responses to low oxygen/oxidative stress by genes involved in Alzheimer’s disease are evolutionarily conserved in fish. Paper1 (thesis chapter in the form of a manuscript) describes the identification of the hmga1 gene in zebrafish which is an orthologue of human HMGA1. It also examines the regulation of this gene under hypoxia/oxidative stress conditions and demonstrates thathmga1 expression is induced under these conditions. However no PS2V-like splice variant of zebrafish psen2 is observed. Paper 2 (thesis chapter in the form of a manuscript) describes the identification of the zebrafish bace1 gene which is orthologous to human BACE1. It also examines the regulation of AD-related genes under hypoxia/oxidative stress. We show that the response of the BACE1-PSEN-APPregulatory axisto hypoxia/oxidative stress is evolutionarily conserved between fish and mammals. Therefore, we also demonstrate that zebrafish are a valid model system for analysis of the effects of hypoxia/oxidative stress on genes associated with Alzheimer’s disease. Advisors/Committee Members: Lardelli, Michael T. (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: hypoxia; zebrafish; oxidative stress

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Moussavi Nik, S. H. (2011). Molecular responses to low oxygen levels/oxidative stress in zebrafish. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/72269

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Moussavi Nik, Seyyed Hani. “Molecular responses to low oxygen levels/oxidative stress in zebrafish.” 2011. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/72269.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Moussavi Nik, Seyyed Hani. “Molecular responses to low oxygen levels/oxidative stress in zebrafish.” 2011. Web. 22 Feb 2020.

Vancouver:

Moussavi Nik SH. Molecular responses to low oxygen levels/oxidative stress in zebrafish. [Internet] [Thesis]. University of Adelaide; 2011. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/72269.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Moussavi Nik SH. Molecular responses to low oxygen levels/oxidative stress in zebrafish. [Thesis]. University of Adelaide; 2011. Available from: http://hdl.handle.net/2440/72269

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

23. Bunting, Mark Daniel. The role of the atypical chemokine receptor CCX-CKR in thymocyte development and its influence on the link between innate and adaptive immunity through regulation of dendritic cell migration.

Degree: 2012, University of Adelaide

URL: http://hdl.handle.net/2440/81780

► The significance of chemokines in directing cell migration both during homeostasis and immune responses has been appreciated for some time. However, the mechanisms in place… (more)

▼ The significance of chemokines in directing cell migration both during homeostasis and immune responses has been appreciated for some time. However, the mechanisms in place to post-translationally regulate cell migration through chemokine modulation are only recently becoming clear. CCX-CKR is a receptor that can scavenge and degrade the ligands of CCR7 and CCR9, two receptors that are crucial during instruction of T cell development in the thymus and dendritic cell migration for initiation of adaptive immune responses. Within the thymus CCL19, CCL21 and CCL25 direct CCR7- and CCR9-expressing thymocytes through distinct thymic compartments, enabling development of a self-MHC restricted and self-tolerant peripheral T cell repertoire. Yet mechanisms outside of transcriptional control that are involved in thymic chemokine regulation have not been well characterised. The aim of this study was to thoroughly investigate the role of CCX-CKR expression on chemokine regulation in the thymus and thymocyte development. Expression of CCX-CKR was detected primarily in cortical thymic epithelial cells, with modest contributions from other thymic stromal populations. Deletion of CCX-CKR led to thymic architecture alterations, reduced levels of CCL19 and CCL25 and a profound decrease in CCL25 (protein) within the cortex. These alterations in chemokine levels and distribution were associated with several defects in the frequency and localisation of thymocyte precursors. Specifically, in CCX-CKR⁻/⁻ thymi, precursor double-negative 2 (DN2) cells accumulated in the medulla and reduced frequencies of DN3 cells were apparent, coincident with reduced numbers of DN3 cells in the cortex. These observations are likely to be the combined outcome of impaired expansion of cortical thymic epithelial cells and reduced outward migration signals in CCX-CKR⁻/⁻ thymi. Additionally, CCXCKR ⁻/⁻ thymi contain increased numbers of CD4⁺CD8⁺ double-positive, CD4⁺ singlepositive and CD8⁺ single-positive cells. Together, these thymic defects were associated with enhanced incidence of inflammatory pathology resembling Sjögren’s syndrome, characterised by lymphocytic infiltrates in salivary glands and liver of 8-10 month old CCX-CKR⁻/⁻ mice. Previous work has implicated CCX-CKR as an important regulator of CCL19 and CCL21 in vivo and deletion of CCX-CKR led to early onset of experimental autoimmune encephalomyelitis (EAE), a T cell mediated autoimmune disease. CCX-CKR was also implicated in promoting effective induction of adaptive immune responses in the LN as evidenced by abrogated T cell proliferation. An important component of both peripheral tolerance induction and initiation of adaptive immune responses is CCR7-dependent migration of antigen-loaded peripheral dendritic cells and naïve T cells to secondary lymphoid organs where antigen presentation to T cells occurs. The contribution of CCXCKR to these processes was investigated in CCX-CKR⁻/⁻ mice. Short-term homing of CD4⁺ T cells to the lymph nodes of CCX-CKR⁻/⁻ mice was impaired yet homeostatic… Advisors/Committee Members: McColl, Shaun Reuss (advisor), School of Molecular and Biomedical Science (school).

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bunting, M. D. (2012). The role of the atypical chemokine receptor CCX-CKR in thymocyte development and its influence on the link between innate and adaptive immunity through regulation of dendritic cell migration. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/81780

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bunting, Mark Daniel. “The role of the atypical chemokine receptor CCX-CKR in thymocyte development and its influence on the link between innate and adaptive immunity through regulation of dendritic cell migration.” 2012. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/81780.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Vancouver:

Bunting MD. The role of the atypical chemokine receptor CCX-CKR in thymocyte development and its influence on the link between innate and adaptive immunity through regulation of dendritic cell migration. [Internet] [Thesis]. University of Adelaide; 2012. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/81780.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bunting MD. The role of the atypical chemokine receptor CCX-CKR in thymocyte development and its influence on the link between innate and adaptive immunity through regulation of dendritic cell migration. [Thesis]. University of Adelaide; 2012. Available from: http://hdl.handle.net/2440/81780

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

24. Lawlor, Kynan Thomas. Investigation of pathways responsible for repeat RNA-mediated cellular perturbation in Drosophila models of dominant expanded repeat disease.

Degree: 2012, University of Adelaide

URL: http://hdl.handle.net/2440/82258

► The expansion of polymorphic repeat sequences within unrelated genes is responsible for pathology in a family of dominant human diseases. Based on clinical and genetic… (more)

▼ The expansion of polymorphic repeat sequences within unrelated genes is responsible for pathology in a family of dominant human diseases. Based on clinical and genetic similarities, it is hypothesised that common pathways may contribute to all of these diseases, with evidence for a number of mechanisms mediated by the expanded repeat. Where the repeats are translated, a long polyglutamine protein has been shown to have pathogenic properties. However, the identification of diseases caused by untranslated repeats has led to the discovery of repeat RNA-mediated pathogenic pathways. As expanded repeat-containing transcripts are present in the case of both translated and untranslated repeats, repeat RNA is a candidate common pathogenic agent. Therefore, determining its contributions to pathology will be important in understanding these diseases. Using the model organism Drosophila melanogaster, this study identifies common CUG and CAG repeat RNA-mediated phenotypes, enabling the investigation of common pathways of cellular perturbation. Ubiquitous expression of either repeat sequence led to reduced viability and disruption to the development of the adult dorsal abdominal tergites through a specific effect on histoblast cells. This phenotype provides a biological read-out of common RNA-mediated effects, enabling examination of the pathways involved by quantifying the changes in the phenotype when specific candidate genes are genetically altered. Tergite disruption was not strongly modified by reducing activity of the well-characterised muscleblind mediated pathway. Furthermore, the presence of specific nuclear RNA foci, an indicator of repeat RNA-mediated protein sequestration, was not correlated with the phenotype. Results indicate that tergite disruption is not strongly dependent on muscleblind sequestration and may involve an alternative pathway. Ectopic expression of either repeat did not cause significant phenotypes in the eye, or neurons, except in the case of one fortuitous transgene insertion. In this case, bidirectional transcription of the repeat tract facilitated by an endogenous promoter was necessary for pathology, providing support for a novel pathway of pathology involving the formation of double-stranded RNA. Subsequent comparison of the pathways involved in hairpin-forming single stranded RNA, and bi-directional double-stranded RNA mediated phenotypes in Drosophila supports the existence of multiple distinct pathways that contribute to cellular perturbation. Advisors/Committee Members: Richards, Robert Ian (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: expanded repeat disease; Drosophila; repeat RNA

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lawlor, K. T. (2012). Investigation of pathways responsible for repeat RNA-mediated cellular perturbation in Drosophila models of dominant expanded repeat disease. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/82258

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lawlor, Kynan Thomas. “Investigation of pathways responsible for repeat RNA-mediated cellular perturbation in Drosophila models of dominant expanded repeat disease.” 2012. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/82258.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lawlor, Kynan Thomas. “Investigation of pathways responsible for repeat RNA-mediated cellular perturbation in Drosophila models of dominant expanded repeat disease.” 2012. Web. 22 Feb 2020.

Vancouver:

Lawlor KT. Investigation of pathways responsible for repeat RNA-mediated cellular perturbation in Drosophila models of dominant expanded repeat disease. [Internet] [Thesis]. University of Adelaide; 2012. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/82258.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lawlor KT. Investigation of pathways responsible for repeat RNA-mediated cellular perturbation in Drosophila models of dominant expanded repeat disease. [Thesis]. University of Adelaide; 2012. Available from: http://hdl.handle.net/2440/82258

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

25. Pham, Duyen H. Gene regulation by Sphingosine kinase.

Degree: 2012, University of Adelaide

URL: http://hdl.handle.net/2440/86477

► Sphingosine kinases (SKs) are lipid kinases that catalyse the phosphorylation of sphingosine to form sphingosine-1-phosphate (S1P), a bioactive phospholipid that plays important roles in a… (more)

▼ Sphingosine kinases (SKs) are lipid kinases that catalyse the phosphorylation of sphingosine to form sphingosine-1-phosphate (S1P), a bioactive phospholipid that plays important roles in a wide variety of cellular processes, including calcium mobilisation, proliferation, apoptosis, angiogenesis, inflammatory responses and cytoskeletal rearrangement. Two SK isoforms exist in mammals, termed SK1 and SK2, which originate from different genes, but possess a high degree of sequence similarity. Although the two enzymes utilise the same substrate, sphingosine, to generate S1P, surprisingly, studies have suggested that SK1 and SK2 may have opposing cellular functions, with SK1 inducing cell survival and SK2 appearing to promote apoptosis. However, the molecular mechanisms mediating these apparently divergent roles for the two SKs have not been extensively examined at present. Furthermore, mouse knockout studies have suggested the two enzymes may have at least some overlapping functions. There is strong evidence implicating SK1 in crucial role(s) in the development and progression of tumourigenesis. However, the mechanism whereby this enzyme induces tumourigenic processes is less clear and remains an important question to be answered in the field. Although high levels of intracellular S1P appears to have a role in regulation of cell proliferation and survival, various observations also suggest a role for extracellular S1P in cell surface G protein-coupled receptor-mediated cell proliferation and survival. However, the specific downstream pathways mediating this oncogenic signalling by SK1 are still poorly defined. In attempts to answer these questions, studies to date have mainly focused on elucidating the cellular signalling pathways that are transiently modulated following SK1 activation. Considerable evidence suggests that SK1 is transcriptionally upregulated in many human cancers and also that its product, S1P, can induce activation of various transcription factors to regulate transcription of other genes. While this type of cellular regulation by SK1 is likely to play an important role in tumourigenesis, no studies have yet been published that systematically examined the molecular mechanisms whereby enhanced SK1 levels lead to oncogenesis. Thus, the main aim of the studies outlined in this thesis was to elucidate the genes regulated by increased cellular SK activity that may be important for normal and pathological cellular regulation. In order to do this, we generated cell lines with tight doxycycline-inducible expression of SK1 and SK2 via a novel approach that involves the incorporation of AU-rich mRNA destabilizing elements (AREs) into the 3’ untranslated regions of the tetracycline-inducible constructs. Use of these tightly controlled SK inducible systems allowed us to perform DNA microarrays and microRNA arrays to elucidate genes and microRNAs regulated soon after a moderate increase in cellular SK levels (approximately 10- and 6-fold overexpression of SK1 and SK2, respectively). This was done to maximise the… Advisors/Committee Members: Pitson, Stuart Maxwell (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: gene; sphingosine kinase; sphingosine 1-phosphate; transferrin receptor 1

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pham, D. H. (2012). Gene regulation by Sphingosine kinase. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/86477

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Pham, Duyen H. “Gene regulation by Sphingosine kinase.” 2012. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/86477.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Pham, Duyen H. “Gene regulation by Sphingosine kinase.” 2012. Web. 22 Feb 2020.

Vancouver:

Pham DH. Gene regulation by Sphingosine kinase. [Internet] [Thesis]. University of Adelaide; 2012. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/86477.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Pham DH. Gene regulation by Sphingosine kinase. [Thesis]. University of Adelaide; 2012. Available from: http://hdl.handle.net/2440/86477

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

26. Simpson, Bradley Guy. Identification of protein-RNA and protein-protein interactions by the neuronal HuC protein of Mus musculus.

Degree: 2013, University of Adelaide

URL: http://hdl.handle.net/2440/87306

► Post-transcriptional gene regulation is an essential process by which all vertebrate organisms regulate gene expression across a wide array of cell types. Such regulation is… (more)

▼ Post-transcriptional gene regulation is an essential process by which all vertebrate organisms regulate gene expression across a wide array of cell types. Such regulation is of particular importance within neurons, as the highly polarised nature of such cells requires that gene expression be tightly regulated in a spatio-temporal manner throughout both proximal and distal regions of the cell. RNA-binding proteins have been shown to regulate a wide range of post-transcriptional regulatory processes, and one family of vertebrate RNA-binding proteins, the Hu family, has been implicated in neuronal specification and differentiation. Of the four proteins in the Hu family, two (HuC and HuD) are uniquely neuronal, whilst one (HuB) is expressed both in neurons and the early embryo. The fourth (HuA) is expressed ubiquitously. Each of the four Hu proteins binds RNA in a sequence-specific manner, mediated by three RNA recognition motifs (RRMs) present in each family member, and are believed to regulate mRNA translation, localisation, and/or message stability. However, little information is currently available regarding the molecular mechanisms by which the neuronal Hu proteins mediate their effects. Thus, whilst HuA has been demonstrated to bind to AU-rich elements (AREs) in the 3’UTRs of a number of labile mRNA messages, little information is currently available regarding the specific RNA sequences that mediate RNA binding by the neuronal Hu proteins. Furthermore, a number of studies have demonstrated that the function of HuA relies upon a number of direct protein-protein interactions. However, to date few interactions have been identified for the neuronal Hu proteins. Identification of the RNA sequences bound by the neuronal Hu proteins and examination of the protein cofactors that mediate the function of these proteins in respect to such bound messages is essential in order to develop an understanding, both of the role played by the neuronal Hu proteins during development, and of the mechanisms by which these functions are achieved. Herein we describe the development of a protocol for the efficient expression and purification of active recombinant HuC, in addition to the subsequent application of this protein to an investigation of the mRNA sequence motifs that mediate RNA binding by this neuronal Hu family member. Moreover, we demonstrate that HuC preferentially binds to RNAs containing short, interspersed uridine-rich sequence motifs in vitro. Additionally, we present evidence which suggests that Hu-bound RNA sequences identified by the Cross-Linking and Immunoprecipitation (CLIP) method do not necessarily represent sites of direct HuC binding, and thus that further study is required in order to identify the complement of mRNAs bound by each neuronal Hu protein. Furthermore, we describe the identification of a number of putative HuC protein-protein interactors by means of yeast two-hybrid analysis, in addition to the development of a protocol for the specific immunoprecipitation of the neuronal Hu proteins. This protocol… Advisors/Committee Members: Jensen, Kirk Blomquist (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: Huc; RNA; post-transcriptional gene regulation; neuronal development; CLIP

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Simpson, B. G. (2013). Identification of protein-RNA and protein-protein interactions by the neuronal HuC protein of Mus musculus. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/87306

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Simpson, Bradley Guy. “Identification of protein-RNA and protein-protein interactions by the neuronal HuC protein of Mus musculus.” 2013. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/87306.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Simpson, Bradley Guy. “Identification of protein-RNA and protein-protein interactions by the neuronal HuC protein of Mus musculus.” 2013. Web. 22 Feb 2020.

Vancouver:

Simpson BG. Identification of protein-RNA and protein-protein interactions by the neuronal HuC protein of Mus musculus. [Internet] [Thesis]. University of Adelaide; 2013. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/87306.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Simpson BG. Identification of protein-RNA and protein-protein interactions by the neuronal HuC protein of Mus musculus. [Thesis]. University of Adelaide; 2013. Available from: http://hdl.handle.net/2440/87306

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

27. Rogers, Nicholas Alan. Expression and functional analysis of SOX3 in murine neurogenesis.

Degree: 2014, University of Adelaide

URL: http://hdl.handle.net/2440/92331

► The Sox (SRY-related HMG box) family of proteins are transcription factors. There are, in total, 30 different genes in the Sox family. Each Sox protein… (more)

▼ The Sox (SRY-related HMG box) family of proteins are transcription factors. There are, in total, 30 different genes in the Sox family. Each Sox protein contains a HMG box (high-mobility-group) which functions as a DNA binding domain. The HMG box is highly conserved (>50% identity) throughout the entire Sox family. Sox3 belongs to the SoxB1 subgroup. SOX3 has been associated with human CNS related disorders. Duplication and mutations of SOX3 have been identified in patients with X-linked hypopituitarism (XH). Afflicted XH patients suffer from varying levels of mental retardation and pituitary hormone deficiencies which can lead to short stature. Previous studies have shown that Sox3 is expressed in nascent neuroprogenitor cells and is functionally required in mammals for development of the dorsal telencephalon and hypothalamus. Using a SOX3-specific antibody, data within my thesis shows that murine SOX3 expression is maintained throughout telencephalic neurogenesis and is restricted to progenitor cells with neuroepithelial and radial glial morphologies. In addition, characterisation of SOX3 expression within the adult neurogenic regions indicates that it is a lifelong marker of neuroprogenitor cells. In contrast to the telencephalon, Sox3 expression within the developing hypothalamus is up-regulated in developing neurons and is maintained in a subset of differentiated hypothalamic cells through to adulthood. In addition, using genome wide expression analysis examining a Sox3 null neural progenitor population, I identified a number of putative Sox3 targets. The data identified Dbx1 as a robust Sox3 target with Dbx1 down-regulation, at both the mRNA and Protein level, within Sox3 null mice at early stages of CNS development. I also independently confirm a number of SOX3 binding sites surrounding Dbx1, with one site showing clear enrichment in vivo. In addition, correlation between these putative targets and that of a previously published SOX3-ChIP data set show a clear enrichment for SOXB1 binding sites near the mis-regulated genes suggesting they are direct targets of Sox3. Taken together, data presented within my thesis identifies new regions of Sox3 expression and putative Sox3 targets. This data helps advance our knowledge of Sox3 regulation and function within CNS development. Advisors/Committee Members: Thomas, Paul Quinton (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: Sox3; neurogenesis; central nervous system; neural progenitor

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rogers, N. A. (2014). Expression and functional analysis of SOX3 in murine neurogenesis. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/92331

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Rogers, Nicholas Alan. “Expression and functional analysis of SOX3 in murine neurogenesis.” 2014. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/92331.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Rogers, Nicholas Alan. “Expression and functional analysis of SOX3 in murine neurogenesis.” 2014. Web. 22 Feb 2020.

Vancouver:

Rogers NA. Expression and functional analysis of SOX3 in murine neurogenesis. [Internet] [Thesis]. University of Adelaide; 2014. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/92331.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Rogers NA. Expression and functional analysis of SOX3 in murine neurogenesis. [Thesis]. University of Adelaide; 2014. Available from: http://hdl.handle.net/2440/92331

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

28. Davey, Philippa Lois. PSC1: a protein with multiple roles in RNA metabolism.

Degree: 2014, University of Adelaide

URL: http://hdl.handle.net/2440/92816

► Peri-implantation stem cell 1 (Psc1) is a developmentally regulated protein that is down regulated as cells of the blastocyst inner cell mass differentiate into primitive… (more)

Subjects/Keywords: SR related protein; RNA metabolism; nuclear speckles; cytospeckle; ES cell

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Davey, P. L. (2014). PSC1: a protein with multiple roles in RNA metabolism. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/92816

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Davey, Philippa Lois. “PSC1: a protein with multiple roles in RNA metabolism.” 2014. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/92816.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Davey, Philippa Lois. “PSC1: a protein with multiple roles in RNA metabolism.” 2014. Web. 22 Feb 2020.

Vancouver:

Davey PL. PSC1: a protein with multiple roles in RNA metabolism. [Internet] [Thesis]. University of Adelaide; 2014. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/92816.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Davey PL. PSC1: a protein with multiple roles in RNA metabolism. [Thesis]. University of Adelaide; 2014. Available from: http://hdl.handle.net/2440/92816

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

29. Whelan, Fiona. The aryl hydrocarbon receptor: structural analysis and activation mechanisms.

Degree: 2010, University of Adelaide

URL: http://hdl.handle.net/2440/95877

► The Aryl-hydrocarbon Receptor (AhR) is a basic Helix-Loop-Helix Per-ARNT-Sim (bHLH.PAS) transcription factor (TF) which binds partner protein Aryl hydrocarbon Receptor Nuclear Translocator (ARNT), in order… (more)

▼ The Aryl-hydrocarbon Receptor (AhR) is a basic Helix-Loop-Helix Per-ARNT-Sim (bHLH.PAS) transcription factor (TF) which binds partner protein Aryl hydrocarbon Receptor Nuclear Translocator (ARNT), in order to activate target genes in response to environmental or endogenous stimuli. The PAS region of these TFs consists of two adjacent repeats of the PAS domain, where the PAS repeat defines dimerization specificity and also serves as a primary sensor in exogenous ligand activation of AhR. Active AhR/ARNT heterodimer binds specific DNA sequences, termed Xenobiotic Response Elements (XRE). The molecular detail of interactions that dictate dimerization and DNA binding specificity are unknown for this TF family. In addition, active AhR has recently been shown to function as a recognition component of an E3 ubiquitin ligase. Reports that AhR null mice have poor fertility and defects in liver vasculature are indicative of the potential for a number of endogenous roles. Research into activation of AhR has highlighted that post-translational modifications may affect function by regulating subcellular localization. The complex regulatory outcomes of AhR expression and activation require a number of approaches to elucidate mechanistic information. In this thesis, a structural investigation of heterodimerization and DNA binding has been used to propose a molecular mechanism for target gene recognition and activation following XRE binding. Crystallographic approaches have yielded crystals of bHLH.PAS-A regions of AhR/ARNT heterodimer bound to DNA. Atomic force microscopy and small angle x-ray scattering analyses have illustrated an XRE binding mechanism whereby the DNA is bent, and the PASA region of the dimer flattens around the DNA. A targeted mutagenesis screen of the AhR ligand binding domain (LBD) was performed to investigate polycyclic aromatic hydrocarbon (PAH) and atypical ligand binding specificity. In parallel, mutant AhR proteins were assessed for inducibility by nonexogenous ligand modes of activation, including cell suspension and application of shear stressed serum. This process identified an LBD mutant selectively activated by novel ligand YH439, and completely inactive following PAH, cell suspension and shear stressed serum treatments, inferring the potential for differential ligand binding pocket access by YH439. Finally, given the complex output following expression and activation of AhR, regulation by post-translational modification was investigated as a potential means of subtle regulation of signalling fate. A thorough analysis of untreated AhR has revealed a concert of modifications occurring on functionally relevant regions of the protein that are implicated in regulating subcellular localization, protein: protein interactions, and potentially, protein stability. Preliminary analyses of YH439 and cell suspension treated AhR has additionally indicated the possibility of activation state specific modification patterns. In summary, this thesis describes: Novel approaches to structural characterisation of a… Advisors/Committee Members: Whitelaw, Murray Leslie (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: aryl hydrocarbon receptor; bHLH; basic Helix Loop Helix; PAS; transcription factor; Dioxin receptor

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Whelan, F. (2010). The aryl hydrocarbon receptor: structural analysis and activation mechanisms. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/95877

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Whelan, Fiona. “The aryl hydrocarbon receptor: structural analysis and activation mechanisms.” 2010. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/95877.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Whelan, Fiona. “The aryl hydrocarbon receptor: structural analysis and activation mechanisms.” 2010. Web. 22 Feb 2020.

Vancouver:

Whelan F. The aryl hydrocarbon receptor: structural analysis and activation mechanisms. [Internet] [Thesis]. University of Adelaide; 2010. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/95877.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Whelan F. The aryl hydrocarbon receptor: structural analysis and activation mechanisms. [Thesis]. University of Adelaide; 2010. Available from: http://hdl.handle.net/2440/95877

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

30. Toledo-Flores, Deborah Fernanda. Evolution of mammalian sex chromosomes and sex determination genes: insights from monotremes.

Degree: 2015, University of Adelaide

URL: http://hdl.handle.net/2440/97382

► Genetic sex determination systems are generally based on the presence of differentiated sex chromosomes. Birds have a ZZ/ZW sex chromosome system in which males are… (more)

▼ Genetic sex determination systems are generally based on the presence of differentiated sex chromosomes. Birds have a ZZ/ZW sex chromosome system in which males are ZZ and females ZW, whereas mammals have an XX/XY system with males being XY and females XX. Monotremes have an extraordinary sex chromosome system that consists of multiple sex chromosomes: 5X5Y in platypus and 5X4Y in echidna. Intriguingly, the monotreme sex chromosomes show extensive homology to the bird ZW and not to the therian XY. However, sex determination in monotremes is still a mystery; the Y-specific Sry gene that triggers male sex determination in therian mammals is absent and so far very few genes have been identified on Y chromosomes in monotremes. To gain more insights into the gene content of Y-chromosomes and to identify potential sex determination genes in the platypus a collaborative large scale transcriptomic approach led to the identification of new male specific genes including the anti-Muellerian hormone AMH that I mapped to Y₅, this makes Amhy an exciting new candidate for sex determination in monotremes. Platypus chromosome 6 is largely homologous to the therian X and therefore it represents the therian proto sex chromosome. In addition, this autosome features a large heteromorphic nucleolus organizer region (NOR) and associates with the sex chromosomes during male meiosis (Casey and Daish personal communication). I investigated chromosome 6 heteromorphism in both sexes and found a number of sex-specific characteristics related to the extent of the NOR heteromorphism, DNA methylation, silver staining patterns and interestingly, meiotic segregation bias. This raises the possibility that chromosome 6 may have commenced differentiation prior to monotreme therian divergence. These results led me to investigate the chromosome 6 borne gene Sox3, from which Sry evolved in therian mammals. This revealed a platypus male-specific Sox3 allele, which differs from the alleles observed also in females on the length of one of the Sox3 polyalanine tracts. This raises the possibility that Sox3 may be working differently in males and females. We have used our unique knowledge of monotreme sex chromosomes to determine the sex of captively bred echidnas. I used a PCR based genetic sexing technique that utilizes DNA from small hair samples and primers that amplify male-specific genes. Interestingly, I found that seven out of eight echidnas born in captivity were females. Furthermore, I found a Sox3 deletion in the only male echidna born in captivity. This gives us the unique opportunity to investigate the sexual development of an animal in which this gene is naturally deleted providing an exceptional situation in which to study monotreme sex determination. Furthermore, this sexing technique has the potential of being applied in the wild to investigate sex ratio in natural populations of monotremes, including the critically endangered long-beaked echidna. Advisors/Committee Members: Grutzner, Frank (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: sex chromosomes; monotremes; platypus; sex determination; Sox3; chromosome 6; heteromorphic autosomes; evolution; echidna; genetic sexing; Amhy; sex-determining factor

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Toledo-Flores, . D. F. (2015). Evolution of mammalian sex chromosomes and sex determination genes: insights from monotremes. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/97382

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Toledo-Flores, Deborah Fernanda. “Evolution of mammalian sex chromosomes and sex determination genes: insights from monotremes.” 2015. Thesis, University of Adelaide. Accessed February 22, 2020. http://hdl.handle.net/2440/97382.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Toledo-Flores, Deborah Fernanda. “Evolution of mammalian sex chromosomes and sex determination genes: insights from monotremes.” 2015. Web. 22 Feb 2020.

Vancouver:

Toledo-Flores DF. Evolution of mammalian sex chromosomes and sex determination genes: insights from monotremes. [Internet] [Thesis]. University of Adelaide; 2015. [cited 2020 Feb 22]. Available from: http://hdl.handle.net/2440/97382.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Toledo-Flores DF. Evolution of mammalian sex chromosomes and sex determination genes: insights from monotremes. [Thesis]. University of Adelaide; 2015. Available from: http://hdl.handle.net/2440/97382

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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