The Role of Rafts in Virus-Induced Membrane Remodeling

筏在病毒诱导的膜重塑中的作用

• 批准号: 7113779
• 负责人: SAMUEL T HESS
• 金额: $ 12.9万
• 依托单位: UNIVERSITY OF MAINE ORONO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-07-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7113779
• 关键词: Orthomyxoviridae; cholesterol; cytoskeletal proteins; fluorescence spectrometry; membrane activity; membrane fusion; membrane lipids; membrane proteins; membrane structure; microorganism hemagglutinin; molecular assembly /self assembly; protein protein interaction; sphingolipids; virus infection mechanism; virus protein

DESCRIPTION (provided by applicant): The applicant has a strong quantitative background in physics, optics, and computers, and has strong interest in research. Further training in biomedical research methods, in particular cell biology and hypothesis-driven science, would enable a broader range of interdisciplinary problems to be attacked, and lead to his successful development as an independent biomedical investigator. The training environment includes the University of Maine, where the P.I. is building a new laboratory and the Institute for Molecular Biophysics. Due to a recent growth in biophysics, the interdisciplinary links between the Institute and the Jackson Laboratory, and the acquisition of the first 4Pi microscope in the U.S., there are many opportunities for highly relevant biomedical research collaborations, symposia, workshops, and team grant writing at the University. Collaborative visits to the NIH, where the mentor runs a well-established laboratory, will provide excellent opportunities for research training, interaction with biomedical experts, and access to equipment. The research plan focuses on the problem of viral infection, which causes considerable mortality. Infection by influenza depends on membrane fusion, which is mediated through the protein HA by a cholesterol- and sphingolipid-sensitive mechanism that likely involves microscopic membrane clusters called rafts. However, the size, shape, mechanism, and dynamics of such domains are currently disputed. This project will use novel, relatively noninvasive fluorescence spectroscopic methods to test whether domains form by partitioning or by direct interaction between HA and lipids. The project will also determine whether the domains are static or dynamic on millisecond and microsecond timescales, and test whether the cytoskeleton mediates domain size or dynamics in cells. Because information about raft dynamics is in shortage, the proposed methods have an unusual advantage. Results will be used to attempt to better understand how influenza virus is able to congregate its own proteins for budding and entry (fusion).

描述（由申请人提供）：申请人在物理、光学、计算机方面有很强的定量背景，并对研究有浓厚的兴趣。生物医学研究方法，特别是细胞生物学和假设驱动科学的进一步培训，将使他能够解决更广泛的跨学科问题，并导致他成功发展为一名独立的生物医学研究者。培训环境包括缅因大学，P.I.正在建设一个新的实验室和分子生物物理研究所。由于生物物理学最近的发展、研究所和杰克逊实验室之间的跨学科联系，以及在美国购买第一台 4Pi 显微镜，有很多机会进行高度相关的生物医学研究合作、研讨会、讲习班和团队资助写作在大学。对 NIH 的合作访问（导师在那里经营着一个完善的实验室）将为研究培训、与生物医学专家互动以及使用设备提供绝佳的机会。 该研究计划的重点是导致大量死亡的病毒感染问题。流感感染依赖于膜融合，膜融合是通过胆固醇和鞘脂敏感机制通过蛋白质 HA 介导的，该机制可能涉及称为筏的微观膜簇。然而，这些域的大小、形状、机制和动态目前存在争议。该项目将使用新型、相对无创的荧光光谱方法来测试结构域是否是通过分配或透明质酸与脂质之间的直接相互作用形成的。该项目还将确定这些域在毫秒和微秒时间尺度上是静态还是动态，并测试细胞骨架是否介导细胞中的域大小或动态。由于筏动力学信息缺乏，所提出的方法具有非同寻常的优势。结果将用于尝试更好地了解流感病毒如何聚集其自身的蛋白质以进行出芽和进入（融合）。