Revealing protein switch design principles through directed evolution

通过定向进化揭示蛋白质开关设计原理

• 批准号: 0828724
• 负责人: Marc Ostermeier
• 金额: $ 39万
• 依托单位: Johns Hopkins University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-10-01 至 2012-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0828724&HistoricalAwards=false
• 关键词: Revealing; protein; switch; design; principles

CBET-0828724OstermeierEngineered protein switches hold great promise as biosensors, selective protein therapeutics and tools for programming cells for biotechnological applications. A lack of understanding switch structure and function limits the ability to create them. Directed evolution approaches to switch construction have been developed by the Principal Investigator (PI). However, for many applications this approach is limited by the ability to screen/select for switches with desired properties. An understanding of switch design principles would greatly facilitate switch construction and enable these applications. The combinatorial nature of directed evolution, when carefully applied, is ideally suited for elucidating these design principles. A series of directed evolution experiments will be performed that are designed to answer specific questions about switch mechanisms and answer practical question on switch construction. The lab of the PI is a multidisciplinary environment. The PI mentors students from several departments and programs at Johns Hopkins University including chemical and biomolecular engineering, biomedical engineering, biology, the chemistry-biology interface program and the computational and molecular biophysics program. Of the seven graduate students the PI currently supervises, five are female and one is of Hispanic descent.

CBET-0828724OsterMeierEnginered蛋白开关作为生物传感器，选择性蛋白质疗法和用于生物技术应用的编程细胞的工具具有很大的希望。缺乏了解开关结构和功能会限制创建它们的能力。首席研究员（PI）开发了定向开关结构的进化方法。但是，对于许多应用程序，此方法受所需属性筛选/选择开关的能力的限制。对开关设计原理的理解将极大地促进开关构建，并启用这些应用。仔细应用时，定向进化的组合性质非常适合阐明这些设计原理。将进行一系列定向的进化实验，旨在回答有关开关机制的特定问题，并回答有关开关构造的实用问题。 PI的实验室是一个多学科的环境。 PI指导约翰·霍普金斯大学多个部门和计划的学生，包括化学和生物分子工程，生物医学工程，生物学，化学生物学界面计划以及计算和分子生物物理学计划。在PI目前监督的七个研究生中，有五名是女性，其中一个是西班牙裔下降。