Date of Award

January 2016

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Agricultural and Biological Engineering

First Advisor

Joseph Irudayaraj

Committee Member 1

Jenna Rickus

Committee Member 2

David Umulis

Committee Member 3

Jean-Christophe Rochet

Abstract

Epigenetics involves a variety of biochemical modifications occurring on chromatin that are able to regulate and fine-tune genetic activities without altering the underlying DNA sequence. So far, four types of epigenetic modulation have been extensively studied: DNA methylation, histone post-translational modification, non-coding RNA, and nuclear organization. A fast-growing body of evidence suggests that epigenetic mechanism plays a fundamental role in physiology and pathology. Of the elucidated epigenetic processes, DNA methylation is the one under intense research due to its direct impact on gene expression, which dynamically bridges the microscale genotype and macroscale phenotype. However, to date our understanding of DNA methylation has primarily come from ensemble and end-point measurements using a population of cells or bulky samples. Unlike genetic aberrations (e.g., amplification, deletion, translocation, and mutation) that are rare to occur and resistant to reverse, events relating to epigenetic modifications take place in a time- and context-dependent manner, thus necessitating nanoscale tools to dissect epigenetic dynamics at a finer spatiotemporal resolution. In my Ph.D. work, a group of advanced single-molecule fluorescence tools, in addition to methodologies in bioengineering, nanotechnology, molecular biology, and bioinformatics, is implemented to approach the DNA methylation-related activities. Furthermore, part of my research aims to translate the new discoveries from single-cell experiments to biomedical applications. Another focus of my dissertation is on effective manipulation of DNA methylation by novel techniques including nanomaterials and optogenetics. Taken together, these efforts lay the groundwork for better understanding of DNA methylation and provide ample avenues for improving epigenetic therapies.

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