Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/139076
Title: ROLE OF COMPRESSIVE FORCE IN ALTERING CHROMATIN CONDENSATION AND ITS APPLICATION FOR CANCER DIAGNOSIS
Authors: KARTHIK DAMODARAN
Keywords: Chromatin condensation, Compressive force, Epigenetics, Cancer diagnosis, Nuclear morphometry, Mechanobiology
Issue Date: 17-Aug-2017
Citation: KARTHIK DAMODARAN (2017-08-17). ROLE OF COMPRESSIVE FORCE IN ALTERING CHROMATIN CONDENSATION AND ITS APPLICATION FOR CANCER DIAGNOSIS. ScholarBank@NUS Repository.
Abstract: Fibroblasts, one of the major type of cells in connective tissue, experience compressive forces (CF) in their local microenvironment. These CFs influence their behaviour by altering chromatin condensation states to regulate genomic programs. However, the mechanistic basis of CF induced alterations in chromatin condensation states is poorly understood. The first part of the thesis shows that CF induces Histone Deacetylase 3 dependent reversible chromatin condensation in fibroblasts resulting in the transcriptionally less active state. This suggests that fibroblasts regulate their chromatin condensation state in response to CFs that allows maintenance of mechanical homeostasis. The second part of the thesis demonstrates the application of compressive force assay and measurement of nuclear morphometric features for early-stage disease diagnosis. Current cancer diagnosis employs various nuclear morphometric measures that have allowed accurate late-stage prognosis. However, the early-stage diagnosis has been a major challenge. We here present a method to detect subtle changes in nuclear morphometric features by combining fluorescence imaging and compressive force assay. Collectively, this work shows how compressive forces are transmitted to regulatory networks in the chromatin and alter their chromatin compaction states which could be exploited to amplify subtle defects in diseased cells for early-stage disease diagnosis.
URI: http://scholarbank.nus.edu.sg/handle/10635/139076
Appears in Collections:Ph.D Theses (Open)

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