About the Project
Emerging evidence suggests that epigenetics plays a major role in gene regulation in heart failure. Epigenetics refers to the heritable regulation of gene expression through modification of chromosomal components without an alteration in the nucleotide sequence of the genome. Three different types of epigenetic variations are known to alter gene expression: modification of histone proteins, methylation of genomic DNA and regulatory noncoding RNAs.
In the proposed project, we aim to use systematic approaches to analyse the profiles of DNA/RNA methylation and histone modification between normal and heart failure/arrhythmic hearts. Thereafter, taking observed changes for further investigations to determine whether these changes are causes or consequences of the disease. Further investigations will take place in genetically-modified animal models and various cellular models, including human cardiomyocytes derived from iPSCs (induced pluripotent stem cells) in the condition of heart failure and induced lethal ventricular arrhythmias.
This project will provide a comprehensive training for a PhD student in systematic and translational medicine with a wealth of molecular and cellular approaches, including next generation RNA sequencing, genome-wide methylation screening and Chip-seq etc, in vivo cardiac functional study (echocardiography, electrocardiography and various surgical procedures) and computational simulation methods.
Informal enquiries may be made directly to the primary supervisor.
Movassagh M, Choy MK, Goddard M, Bennett MR, Down TA, Foo RS.
Differential DNA methylation correlates with differential expression of angiogenic factors in human heart failure. PLoS One. 2010;5:e8564.
Tingare A, Thienpont B, Roderick HL. Epigenetics in the heart: the role of histone modifications in cardiac remodelling. Biochem Soc Trans. 2013 Jun;41(3):789-96.
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