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dc.contributor.authorTabar, Mehdi Sharifi
dc.date.accessioned2019-06-13
dc.date.available2019-06-13
dc.date.issued2019-06-13
dc.identifier.urihttp://hdl.handle.net/2123/20547
dc.description.abstractThis thesis presents data to enhance our understanding of the composition, assembly, and structure of the nucleosome remodeling and deacetylase (NuRD) complex, a transcriptional coregulator that is strongly linked to cancer. Understanding the structure and function of the gene regulating complexes will lead to a better understanding of mechanisms of gene regulation. This should ultimately both allow insight into disease processes that originate from gene regulatory network malfunction and might enable reprogramming of the gene expression for application in health, agriculture and industry. Chapter 1 represents a general introduction to gene regulation and the NuRD complex. The NuRD complex is a 1mDa multisubunit transcriptional coregulator protein complex, which is widely expressed and harbours both chromatin remodelling and histone deacetylase activities. Abnormalities in a number of its components are associated with various types of cancers and neurodegenerative diseases. Although the core components of the complex have been well established, the structural basis of the complex has poorly been studied. Chapter 2 describes the details of the materials and methods used in this research. Chapter 3 investigates NuRD complex stoichiometry and interactome using a label-free quantitative proteomics method and provides biochemical evidence for two new direct interactors of the complex. Chapter 4 and 5 investigate the recombinantly produced subcomplexes using biochemical and a mass spectrometry-based hybrid method for structural modelling of the NuRD complex. Chapter 6 discuss the findings and outlines the future directions.en_AU
dc.publisherUniversity of Sydneyen_AU
dc.publisherFaculty of Scienceen_AU
dc.publisherSchool of Life and Environmental Sciencesen_AU
dc.rightsThe author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.en_AU
dc.subjectNuRD complexen_AU
dc.subjectprotein-protein iteractionen_AU
dc.subjectXL-MS/MSen_AU
dc.subjectStoichiometryen_AU
dc.subjectProteomicsen_AU
dc.titleUnderstanding the Architecture, Assembly, and Interactome of the Nucleosome Remodelling and Deacetylase (NuRD) Complexen_AU
dc.typePhD Doctorateen_AU
dc.type.pubtypeDoctor of Philosophy Ph.D.en_AU


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