Investigating the Epigenetic Correlation Between Disease and Aging

DNA methylation (DNAme) refers to the addition of a methyl group to the cytosines of the CpG islands in the gene regulatory regions, which is involved in regulating transcription and chromatin structure, typically silencing the corresponding genetic locus. A lifetime of accumulated epigenetic changes has been proposed to contribute to the development of age-associated diseases. I aim to investigate the biological relevance of DNA methylation clocks via Elastic Net regression approaches and to develop a better model by which chronological age could be correlated with the disease through epigenetics. Meanwhile, DNAme changes with age in a direction that differs per individual, which suggests epigenetic variations to be higher among the elderly compared to younger individuals. I will examine the interindividual variation of DNAme using the output of DNAme arrays and annotate the age-variable CpGs to the candidate biological age-relevant genes/proteins based on the Conboy lab screens, by conventional and bio-orthogonal […]

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ATP7B-/- Knockout Mice as a Model for Wilson's Disease Sleep Disorders

Up to half of Wilsons disease patients suffer from sleep disorders, including poor sleep quality, REM behavioral disorders (RBD), and cataplexy. However, the neural basis of these symptoms is poorly understood. My project this summer is to determine whether the ATP7B-/- knockout mouse is a good model system for studying the sleep disorders manifested in Wilsons disease, especially in the context of neural pathways involving copper homeostasis. Using automated sleep scoring methods, we will quantify sleep signatures in ATP7B-/- knockout and wildtype control mice. The brain copper changes in recorded mice will then be analyzed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to create a map of copper distribution from which key brain regions associated with sleep changes can be identified. The ATP7B-/- knockout mouse has the potential to be incredibly useful in studying neurological symptoms and sleep disorders in Wilsons disease patients, as well as for REM […]

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