The Interplay Between Membrane Structure and Protein Interactions

膜结构与蛋白质相互作用之间的相互作用

• 批准号: 1413613
• 负责人: Ka Yee Lee
• 金额: $ 114.82万
• 依托单位: University of Chicago
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1413613&HistoricalAwards=false
• 关键词: Interplay; Between; Membrane; Structure; Protein

In this research project, the PI will establish a comprehensive paradigm for understanding the mechanisms by which membrane-binding peptides and proteins distinguish one membrane from another. This is a fundamentally important question in biology and will be explored in the context of immune response, focusing on two canonical examples of immune targeting of membranes during immune response. This paradigm will advance knowledge in multiple disciplines by providing a foundation for understanding how proteins selectively recognize membrane targets. The project will also form a union between a multitude of experimental techniques and thereby contribute to many scientific fields including, but not limited to, molecular immunology, membrane biophysics, and interfacial x-ray and neutron scattering.The proposed research activities will provide training opportunities in a highly interdisciplinary area, and will help train the next generation of interdisciplinary scientists. The PI will further enhance the content of a graduate course in membrane biophysics, as well as the curriculum development of a new interdisciplinary degree-granting program in Biophysical Sciences. Apart from graduate students and postdocs, research opportunities will be extended to qualified high school, undergraduate, summer research as well as international exchange students. The PI has spearheaded and will continue to run a 7-week summer research program, placing 14 rising high school seniors from the University of Chicago Laboratory Schools in laboratories across the Biological and Physical Sciences Divisions at the University of Chicago. It is the hope that an early exposure to research can help entice these young students to consider a career in science. The PI will continue to host undergraduate and REU student for research in the laboratory. Science, especially the concept of interdisciplinary science, will be brought to school children through outreach activities, including participating in 'Physics with a Bang!', and performing science demonstrations to lower school students. The PI is committed to increasing the representation of women in academic science. Efforts will be made to address the opportunities for women in academic science through the PI's work with the Provost Office and her involvement in the Women in Physical Sciences Division Committee at the University of Chicago as well as the Chicago Women in STEM organization in the Greater Chicago Area.The understanding of the membrane bilayer has evolved from a simple mosaic system to one with a complicated heteregeneous lateral structure. The elucidation of how different lipids species within a membrane interact with one another, and how these interactions give rise to the defining properties of lipid membranes has provided fundamental insight into the organization and structure of lipid membranes. The project leverages expertise in the characterization of membrane systems, using model membrane systems and exploiting a suite of biophysical techniques (surface-pressure measurements, optical microscopy, fluorescence binding assays, atomic force microscopy, x-ray and neutron scattering) to provide new perspectives on two fundamental and reciprocally related questions:(1) How do membrane properties influence interactions with membrane targeting peptides and proteins?(2) How does the interaction of peptides and proteins alter the properties of a given membrane?The project specifically addresses these central questions in the context of immune response, focusing on two canonical examples of immune targeting of membranes during immune response: the disruption of pathogenic membranes by antimicrobial peptides (AMPs) and the recognition of phosphatidylserine (PS) lipids exposed on the extracellular leaflet of host cells as an effector of immune regulation. Both AMPs and peripheral PS membrane binding proteins have been hypothesized to employ sensitivity to differences in membrane properties to mediate their differential recognition properties. Thus the primary focus of this project is to first establish the sensitivities of a representative AMP (protegrin-1) and PS receptor family (T-cell Immunoglobulin and Mucin-containting or TIM) to fundamental membrane properties. Additionally, the project also aims to reciprocally understand how the interactions of these peptides and proteins alter the underlying membrane properties.

在这个研究项目中，PI将建立一个全面的范例来理解膜结合肽和蛋白质区分不同膜的机制。这是生物学中一个基本的重要问题，将在免疫反应的背景下进行探索，重点讨论免疫反应过程中以膜为免疫靶点的两个典型例子。这一范例将为理解蛋白质如何选择性地识别膜靶标提供基础，从而推动多学科的知识进步。该项目还将形成多种实验技术的联合，从而为许多科学领域做出贡献，包括但不限于分子免疫学、膜生物物理学、界面X射线和中子散射。拟议的研究活动将在一个高度交叉的领域提供培训机会，并将有助于培训下一代跨学科科学家。PI将进一步加强膜生物物理学研究生课程的内容，以及生物物理科学新的跨学科学位授予方案的课程开发。除了研究生和博士后，研究机会将扩大到合格的高中、本科生、暑期研究以及国际交换生。PI已经带头并将继续开展为期7周的暑期研究项目，将来自芝加哥大学实验室学院的14名高三学生安排在芝加哥大学生物科学和物理科学系的实验室中。人们希望，及早接触研究可以帮助吸引这些年轻学生考虑从事科学事业。PI将继续接待本科生和REU学生进行实验室研究。科学，特别是跨学科科学的概念，将通过外展活动带给学童，包括参加《物理学与爆炸》，以及向低年级学生进行科学示范。国际和平研究所致力于增加女性在学术科学中的代表性。将努力通过PI与教务长办公室的工作以及她参与芝加哥大学物理科学妇女分部委员会以及大芝加哥地区的芝加哥STEM妇女组织来解决妇女在学术科学中的机会。对膜双层的理解已经从一个简单的马赛克系统发展到具有复杂的异质横向结构。阐明了膜中不同的脂类如何相互作用，以及这些相互作用如何引起脂膜的明确性质，这为人们对脂膜的组织和结构提供了基本的见解。该项目利用膜系统表征方面的专业知识，使用模型膜系统，并利用一套生物物理技术(表面压力测量、光学显微镜、荧光结合分析、原子力显微镜、X射线和中子散射)来为两个基本且相互关联的问题提供新的视角：(1)膜性质如何影响与膜靶标多肽和蛋白质的相互作用？(2)多肽和蛋白质的相互作用如何改变给定膜的性质？该项目专门在免疫反应的背景下解决这些核心问题，重点介绍在免疫应答过程中以膜为免疫靶向的两个典型例子：抗菌肽(AMPs)破坏致病性膜和识别暴露在宿主细胞胞外小叶上的磷脂酰丝氨酸(PS)脂类作为免疫调节的效应器。AMPs和外周PS膜结合蛋白都被假设为利用对膜性质差异的敏感性来调节它们的差异识别性质。因此，这个项目的主要焦点是首先建立一个具有代表性的AMP(Protigin-1)和PS受体家族(T细胞免疫球蛋白和粘蛋白-含或TIM)对基本膜特性的敏感性。此外，该项目还旨在相互了解这些多肽和蛋白质的相互作用如何改变潜在的膜特性。