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

【摘要】backman， vadim本研究旨在理解纳米尺度上的生物过程，这一过程一直受到缺乏实用的细胞纳米结构分析手段的阻碍。传统的可见光显微镜只能在微观尺度上检测形态变化。为了解决这一限制，PI？我们已经开发了PWS显微镜，可以量化细胞纳米结构的统计特性。使用PWS，他们证明了在癌变的早期阶段，核纳米结构紊乱的增加表现为高阶染色质结构的改变。这种现象在多种类型的癌症（肺癌、结肠癌、胰腺癌、食道癌、卵巢癌和甲状腺癌）中都有观察到。这个项目将导致一种新的基于光散射干涉的显微镜技术的发展，分子PWS （mPWS）显微镜，这将允许在纳米尺度上对细胞染色质结构进行分子特异性的传感，这是不可能的。该技术将用于研究高阶染色质结构变化如何调节基因转录的表观遗传机制。提出的工作旨在描述与染色质纳米环境变化相关的所有这些不同过程。

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.