EAGER: New Biophotonics and Computational Molecular Dynamics for Understanding Epigenetic Regulation of Gene Transcription

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ABSTRACT#1249311Backman, VadimThis proposal aims to understand biological processes at the nanoscale that has been stymied by a lack of practical means of analysis of cellular nanoscale architecture. Conventional visible-light microscopy allows detection of morphological changes only at the micro-scale. To address this limitation, the PI?s have developed PWS microscopy, which quantifies the statistical properties of cellular nanoarchitecture. Using PWS, they demonstrated an increase in the disorder of nuclear nanoarchitecture in the earliest stages of carcinogenesis manifested as an alteration of the higher-order chromatin structure. This phenomenon was observed in multiple cancer types (lung, colon, pancreatic, esophageal, ovarian and thyroid cancers). This project will lead to the development of a new light-scattering interference-based microscopy technique, molecular PWS (mPWS) microscopy, which would allow molecular-specific sensing of cell chromatin structure at the nanoscale, which is not otherwise possible. The technique will be used to study epigenetic mechanisms of how changes in higher order chromatin structure modulate gene transcription. The proposed work is aimed at describing all these different processes related to the changes in the chromatin nanoenvironment.