A network analysis based proteomic and transcriptomic investigation into HIV-Tat induced neuronal dysfunction and the neuroprotective effect of lithium

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dc.contributor.advisorBlackburn, Jonathan Men_ZA
dc.contributor.authorGanief, Tariq Ahmaden_ZA
dc.date.accessioned2017-01-17T12:21:28Z
dc.date.available2017-01-17T12:21:28Z
dc.date.issued2016en_ZA
dc.description.abstractHIV-associated neurocognitive disorders (HAND) affect up to 70% of HIV positive individuals and are the leading cause of dementia in patients under 40 years. Despite this, the molecular mechanisms involved in the onset of HAND are not well understood. Among a number of plausible etiological agents of HAND, HIV-Tat has been shown to be neurotoxic in vitro and in vivo, but the basis of its induced neuronal dysregulation remains relatively poorly characterised, giving rise to various competing theories. This thesis describes differential, quantitative proteomic analyses of HIV-Tat-treated neuronal cells in vitro, the goal being to gain deeper insight into the underlying molecular basis of this HIV-Tat-mediated dysregulation, as well as to potentially inform better patient treatments in the future. To achieve this goal, deep, quantitative proteomic analysis of HIV-Tat treated SILAC-labelled SH-SY5Y neuroblastoma cells was carried out, alongside transcriptomic analysis of the same system in which 3077 proteins were identified and quantified with 407 proteins and 1074 genes being differentially expressed. Subsequently, label-free proteomics analysis was used to study the ability of lithium - a proposed new treatment for HAND - to suppress the HIV-Tat induced dysregulated molecular phenotype in SH-SY5Y cells in which 3757 were identified and quantified with 360 and 531 being significantly differentially expressed in HIV-Tat and HIV-Tat + lithium treated cells, respectively.en_ZA
dc.identifier.apacitationGanief, T. A. (2016). <i>A network analysis based proteomic and transcriptomic investigation into HIV-Tat induced neuronal dysfunction and the neuroprotective effect of lithium</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Division of Medical Biochemistry. Retrieved from http://hdl.handle.net/11427/22759en_ZA
dc.identifier.chicagocitationGanief, Tariq Ahmad. <i>"A network analysis based proteomic and transcriptomic investigation into HIV-Tat induced neuronal dysfunction and the neuroprotective effect of lithium."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Division of Medical Biochemistry, 2016. http://hdl.handle.net/11427/22759en_ZA
dc.identifier.citationGanief, T. 2016. A network analysis based proteomic and transcriptomic investigation into HIV-Tat induced neuronal dysfunction and the neuroprotective effect of lithium. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Ganief, Tariq Ahmad AB - HIV-associated neurocognitive disorders (HAND) affect up to 70% of HIV positive individuals and are the leading cause of dementia in patients under 40 years. Despite this, the molecular mechanisms involved in the onset of HAND are not well understood. Among a number of plausible etiological agents of HAND, HIV-Tat has been shown to be neurotoxic in vitro and in vivo, but the basis of its induced neuronal dysregulation remains relatively poorly characterised, giving rise to various competing theories. This thesis describes differential, quantitative proteomic analyses of HIV-Tat-treated neuronal cells in vitro, the goal being to gain deeper insight into the underlying molecular basis of this HIV-Tat-mediated dysregulation, as well as to potentially inform better patient treatments in the future. To achieve this goal, deep, quantitative proteomic analysis of HIV-Tat treated SILAC-labelled SH-SY5Y neuroblastoma cells was carried out, alongside transcriptomic analysis of the same system in which 3077 proteins were identified and quantified with 407 proteins and 1074 genes being differentially expressed. Subsequently, label-free proteomics analysis was used to study the ability of lithium - a proposed new treatment for HAND - to suppress the HIV-Tat induced dysregulated molecular phenotype in SH-SY5Y cells in which 3757 were identified and quantified with 360 and 531 being significantly differentially expressed in HIV-Tat and HIV-Tat + lithium treated cells, respectively. DA - 2016 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2016 T1 - A network analysis based proteomic and transcriptomic investigation into HIV-Tat induced neuronal dysfunction and the neuroprotective effect of lithium TI - A network analysis based proteomic and transcriptomic investigation into HIV-Tat induced neuronal dysfunction and the neuroprotective effect of lithium UR - http://hdl.handle.net/11427/22759 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/22759
dc.identifier.vancouvercitationGanief TA. A network analysis based proteomic and transcriptomic investigation into HIV-Tat induced neuronal dysfunction and the neuroprotective effect of lithium. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Division of Medical Biochemistry, 2016 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/22759en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDivision of Medical Biochemistryen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherIntegrative Biomedical Sciencesen_ZA
dc.titleA network analysis based proteomic and transcriptomic investigation into HIV-Tat induced neuronal dysfunction and the neuroprotective effect of lithiumen_ZA
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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