DNA phase-separation as a general mean of regulating gene expression in hybrid cells

DNA 相分离作为调节杂交细胞中基因表达的一般手段

基本信息

批准号：
2451637
负责人：
金额：
--
依托单位：
Imperial College London
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2020
资助国家：
英国
起止时间：
2020 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2451637
关键词：
DNA phase separation general mean

项目摘要

Liquid-liquid phase separation is increasingly recognised as a key mechanism to regulate gene expression in living cells by controlling the accessibility of genetic material and its co-localisation with transcription machinery. Although mechanisms that trigger phase separation in biological cells are not fully understood, a similar control of transcriptional activation could be recapitulated in hybrid cells, engineered from the bottom-up by combining biological and man-made components. Programming the condensation of genetic material (DNA) and its co-localisation with cellular machinery is a particularly promising approach to regulate transcription. DNA aggregation can be induced by wellunderstood canonical and non-canonical secondary structures, and its occurrence can thus be controlled by a variety of physical stimuli, including temperature, crowding agents and exposure to certain ions. Herein, we propose to generate a hybrid cell system that can be transcriptionally activated by triggering nucleic-acid phase separation, offering an orthogonal solution to current methods that fully rely on small-molecule treatment (e.g. IPTG) and cannot be controlled easily by physical means. Besides offering an alternative method to regulate gene-expression in artificial cells, this project will yield insights on the fundamental physical processes that might be responsible of gene-regulation via liquid-liquid phase separation in living cells

通过控制遗传材料的可及性及其与转录机械的共定位，液态液相分离越来越多地被认为是调节活细胞中基因表达的关键机制。尽管尚未完全了解触发生物细胞中相位分离的机制，但可以通过结合生物学和人造成分来从自下而上设计的杂化细胞中概括转录激活的类似控制。编程遗传材料（DNA）的凝结及其与细胞机械的共定位是调节转录的一种特别有前途的方法。 DNA聚集可以通过良好的规范和非典型的二级结构来诱导，因此可以通过多种物理刺激（包括温度，拥挤的剂和暴露于某些离子暴露）来控制其发生。本文中，我们建议生成一个可以通过触发核酸相分离来转录激活的杂化细胞系统，为完全依赖小分子处理（例如IPTG）的当前方法提供正交溶液（例如IPTG），并且无法通过物理手段轻松控制。除了提供一种调节人造细胞中基因表达的替代方法外，该项目还将对可能导致基因调节的基本物理过程进行见解