Mechanisms of Acquired Immunity in Bacteria

题目：细菌获得性免疫机制高级人员：Jennifer Doudna，加州大学伯克利分校（主要研究者）科学研究：控制细菌群体中的病毒感染对微生物的广泛应用至关重要，包括生物修复和生物燃料生产。在细菌中发现基于rna的获得性免疫，由簇状规则间隔短回文重复序列（crispr）介导，如果潜在的分子机制可以被发现和操纵，这为利用调节基因表达的自然途径提供了一个令人兴奋的机会。该项目旨在确定如何实现自我与非自我识别，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抗未来的感染。这个项目有可能改变我们理解细菌基因调控的方式，并揭示以前未知和意想不到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通路的独立进化和生理功能，有必要确定CRISPR活性的分子机制。这个项目的潜在影响包括发现微生物获得对病毒免疫的机制，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，尤其吸引那些第一次接触蛋白质和RNA生物化学的本科生。学生们有很多机会在这个领域做出真正的新发现，这些发现可能会产生非常大的影响。更广泛的影响：主要研究者的实验室在使用各种实验方法对涉及RNA和RNA-蛋白质复合物的分子机制进行创造性解剖方面培养了各级学生的成功历史。该项目将在加州大学伯克利分校的一个高度协作的环境中进行，加州大学伯克利分校已经成为CRISPR研究的事实上的中心，包括吉尔·班菲尔德、菲尔·休根霍兹和亚当·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。学生们参加并在会议上展示他们的作品，为学习和讨论新的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.