Dissecting nuclear protein dynamics and structural changes with single-molecule spectroscopy and microscopy

Liu, Wenjie

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https://hdl.handle.net/2142/116033 Copy

Description

Title

Dissecting nuclear protein dynamics and structural changes with single-molecule spectroscopy and microscopy

Author(s)

Liu, Wenjie

Issue Date

2022-06-29

Director of Research (if dissertation) or Advisor (if thesis)

Irudayaraj, Joseph

Doctoral Committee Chair(s)

Irudayaraj, Joseph

Committee Member(s)

• Cunningham, Brian
• Underhill, Gregory
• Bhargava, Rohit

Department of Study

Bioengineering

Discipline

Bioengineering

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

epigenetics, single-molecule

Abstract

Cancer is one of the most significant causes of mortality in the United States, with approximately 1 in 4 individuals likely to develop cancer during their lifespan. Unfortunately, despite the enormous effort in cancer diagnosis and therapy, the mortality rate is still high because of multiple challenges imposed by cancer relapse, metastasis, and drug resistance. The origin of such tragedy lies in the heterogeneity of tumors featuring various cellular morphology, genomics, and epigenomics. Tumor heterogeneity is linked with genetic mutations, epigenetic alterations, and external pressure from the tumor microenvironment. Biochemical approaches such as next-generation sequencing can elucidate the genetic origins of heterogeneity. Recent literature has shown that epigenetic modifications play a prominent role in modulating transcription, yet limited knowledge exists in the mechanistic understanding of such changes in the context of living cell. Understanding how epigenetic modifications affect the state of chromatin and discovering phenotypical epigenetic states are critical for advanced cancer detection and treatment. This work evaluated how external cues, such as environmental toxicants, pharmaceutical drugs, and tumor microenvironment, could affect chromatin and its dynamic states with single-molecule fluorescence tools in living cells. To develop a mechanistic basis, single-molecule tools were used to track and identify cells that exhibit phenotypical epigenetic traits, linking specific epigenetic modifications in response to drug treatment and tumor progression.

Graduation Semester

2022-08

Type of Resource

Thesis

Copyright and License Information

Copyright 2022 Wenjie Liu

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