Mechanisms of Acquired Immunity in Bacteria

高级人员：加州大学伯克利分校的Jennifer Doudna(首席研究员)科学研究：控制细菌群体中的病毒感染对将微生物用于广泛的应用至关重要，包括生物修复和生物燃料生产。在细菌中发现了由簇状规则间隔短回文重复序列(CRISPR)介导的基于RNA的获得性免疫，这为探索调控基因表达的自然途径提供了令人兴奋的机会，如果潜在的分子机制能够被发现和操纵的话。该项目旨在确定如何实现自我与非我的识别，如何在病毒感染期间获得新的DNA序列，并用于免疫细胞以抵御未来的感染。该项目有可能改变我们对细菌中基因调控的理解方式，并揭示一种以前未知和未曾预料的抗病毒防御机制的分子基础。为了了解利用RNA分子控制遗传元件的细菌途径的独立进化和生理功能，有必要确定CRISPR活性的分子机制。该项目的潜在影响包括发现微生物获得病毒免疫力的机制，以及为各种应用提供操纵或设计这些系统所需的知识。该项目为学生提供了一个令人兴奋的研究途径，对第一次接触蛋白质和RNA生物化学的本科生特别有吸引力。学生们有大量的机会在这一领域做出真正的新发现，潜在的影响非常大。广泛的影响：主要研究者的实验室有成功的历史，培训各级学生使用各种实验方法创造性地剖析涉及RNA和RNA-蛋白质复合体的分子机制。该项目将在加州大学伯克利分校高度协作的环境中进行，该校已成为CRISPR研究的事实上的中心，包括吉尔·班菲尔德、菲尔·胡根霍尔茨和亚当·阿金的实验室正在进行的工作。一年一度的CRISPR会议吸引了来自世界各地的科学家来到加州大学伯克利分校分享他们的最新成果。学生们出席并在会上展示了他们的工作，为学习和讨论新成果提供了一个绝佳的机会。

Title: Mechanism of Acquired Immunity in BacteriaSenior personnel: Jennifer Doudna, University of California at Berkeley (Principle investigator)Scientific research: Control of viral infections in bacterial populations is critical to the use of microbes for a wide variety of applications including bioremediation and biofuel production. The discovery of RNA-based acquired immunity in bacteria, mediated by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs), provides an exciting opportunity to exploit natural pathways for regulating gene expression if the underlying molecular mechanisms can be discovered and manipulated. This project aims to determine how self versus non-self recognition is achieved, how new DNA sequences are acquired during viral infections and used to immunize cells against future infections. This project has the potential to transform the way we understand gene regulation in bacteria, and to reveal the molecular basis for a previously unknown and unanticipated mechanism of anti-viral defense. To understand the independent evolution and physiological functions of bacterial pathways utilizing RNA molecules to control genetic elements, it will be necessary to determine the molecular mechanisms of CRISPR activity. The potential impact of this project includes both discovering the mechanisms by which microbes acquire immunity to viruses, and providing the knowledge necessary to manipulate or engineer those systems for various applications. The project provides an exciting avenue of research for students, and is particularly appealing to undergraduates who are being exposed to protein and RNA biochemistry for the first time. There are ample opportunities for students to make truly new discoveries in this field, with potentially very high impact.Broader impacts: The primary investigator's lab has a successful history of training students at all levels in the creative dissection of molecular mechanisms involving RNA and RNA-protein complexes using a variety of experimental methods. The project will be conducted in a highly collaborative environment at UC Berkeley, which has become a de facto center for CRISPR research encompassing ongoing work in the laboratories of Jill Banfield, Phil Hugenholtz and Adam Arkin. An annual CRISPR conference attracts scientists from around the world to UC Berkeley to share their latest results. Students attend and present their work at this meeting, providing an outstanding opportunity for learning and discussing new results.