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细菌免疫系统调控的生物物理模型

Biophysical modeling of bacterial immune system regulation
课程网址: http://videolectures.net/biophysics2018_djordjevic_system_regulat...  
主讲教师: Marko Djordjević
开课单位: 贝尔格莱德大学
开课时间: 2018-07-09
课程语种: 英语
中文简介:

细菌免疫系统(CRISPR Cas和限制性修饰系统)可以保护细菌细胞免受病毒或质粒的侵袭。 CRISPR Cas也发现了主要的生物技术应用,但要优化利用它们,有必要了解该系统在细菌中的天然功能。 CRISPR Cas通常在正常条件下处于沉默状态,而理解CRISPR Cas功能的主要问题之一是如何诱导这种通常处于沉默状态的系统,这很难直接通过实验观察。因此,CRISPR Cas诱导机制目前尚不清楚,这项工作的主要目标是使用计算模型来了解CRISPR Cas激活中关键特征的作用,并为CRISPR Cas诱导提出一个现实的实验模型。为了解决这些问题,我们使用系统转录调控的热力学模型,以及相关分子种类(RNA和蛋白质)的动力学模型。此外,更多的基本细菌免疫系统(限制性修饰)在其转录调控中表现出与CRISPR Cas相似的特征,并且可能在其功能上面临相似的动力学约束。因此,我们还对具有不同体系结构的细菌限制性修饰系统的调控进行建模,并提出相同的设计原则可能会落后于两种细菌免疫系统的调控。在机械上不同的系统(在这种情况下为CRISPR Cas和限制性修饰系统)背后找到相同的设计原理,也是系统生物学的主要目标。

课程简介: Bacterial immune systems (CRISPR-Cas and restriction-modification systems) defend bacterial cells against invasion by viruses or plasmids. CRISPR-Cas has also found major biotechnology applications, but to optimally exploit them, it is necessary to understand native function of this system in bacteria. CRISPR-Cas is typically silent under normal conditions, and one of the main questions in understanding CRISPR-Cas functioning is how this normally silent system is induced, which is very hard to directly experimentally observe. Consequently, CRISPR-Cas induction mechanism is currently unknown, and the main goal of this work is to use computational modeling to understand the role of the key features in CRISPR-Cas activation, and to propose a realistic experimental model for CRISPR-Cas induction. To address these questions, we use thermodynamical modeling of the system transcription regulation, and dynamical modeling of the relevant molecular species (RNA and proteins). Furthermore, much more rudimental bacterial immune systems (restriction-modification) exhibit similar features in their transcription regulation as CRISPR-Cas, and likely face similar dynamical constraints in their functioning. Consequently, we also model regulation of bacterial restriction-modification systems with different architectures, and propose that the same design principles may be behind regulation of both bacterial immune systems. Finding the same design principles behind mechanistically otherwise different systems (in this case CRISPR-Cas and restriction-modification systems) is also a major goal of systems biology.
关 键 词: 细菌免疫系统; 热力学模型; 系统生物学
课程来源: 视频讲座网
数据采集: 2020-11-22:cjy
最后编审: 2020-11-22:cjy
阅读次数: 29