Stem Cell Research Group Honours Project #4: Defining the role of DNA methylation in cancer stem cells CONTACT EMAIL: [email protected] Background: Cancer stem cells are rare cells within a cancer that are central to the growth of cancers and their therapeutic resistance. Abnormalities of DNA methylation has been recognised for more than 20 years but how these changes arise and whether they contribute to cancer stem cells remain major unanswered questions in cancer biology. We have recently identified genome wide DNA hypermethylation in cancer stem cells. Project: This project will use cutting edge technologies to address fundamental questions about DNA methylation during cancer development. The project will have three specific aims. First, you will use chromatin immunoprecipitation and bioinformatics to determine if the DNA hypermethylation changes are found at promoters enriched for targets of the polycomb repressor complex 2. Second, you will determine if EZH2 is required for DNA hypermethylation. Finally, you will determine if the demethylating agent azacitidine can reverse hypermethylation changes and if so, whether it can kill or sensitize cancer stem cells. The student will acquire a broad range of skills including bioinformatics analyses, ChIP, and analysis of transgenics (flow cytometry, transplant assays) in a dynamic, large research environment. Outcome: This project will determine if hypermethylation in cancer is mediated by aberrant PRC2 function and can be reversed by targeting the methyltransferases EZH2 or DNMTs.
Posted on: Mon, 29 Jul 2013 23:26:04 +0000
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