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: 6955627
• 负责人: SAMUEL T HESS
• 金额: $ 12.4万
• 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/6955627
• 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).

应聘者描述(申请人提供)：应聘者在物理、光学和计算机方面有很强的量化背景，对研究有浓厚的兴趣。生物医学研究方法的进一步培训，特别是细胞生物学和假说驱动的科学，将使他能够解决更广泛的跨学科问题，并使他成功地发展为一名独立的生物医学研究员。培训环境包括缅因州大学，P.I.正在那里建造一个新的实验室，以及分子生物物理研究所。由于最近生物物理学的发展，研究所和杰克逊实验室之间的跨学科联系，以及美国第一台4PI显微镜的获得，该大学有许多高度相关的生物医学研究合作、研讨会、研讨会和团队拨款撰写的机会。合作访问NIH，导师在那里运营着一个完善的实验室，将为研究培训、与生物医学专家的互动和获得设备提供极好的机会。 该研究计划的重点是病毒感染问题，这会导致相当大的死亡率。流感的感染依赖于膜融合，膜融合是通过HA蛋白介导的，这种融合是通过一种对胆固醇和鞘脂敏感的机制来实现的，这种机制可能涉及被称为筏子的微小膜团。然而，这些区域的大小、形状、机制和动力学目前存在争议。该项目将使用新颖的、相对非侵入性的荧光光谱方法来测试结构域是通过分割还是通过HA和脂类之间的直接相互作用形成的。该项目还将确定结构域在毫秒和微秒时间尺度上是静态的还是动态的，并测试细胞骨架是否调节结构域的大小或细胞中的动态。由于缺乏关于筏板动力学的信息，所提出的方法具有不同寻常的优势。结果将被用来试图更好地理解流感病毒如何能够聚集自己的蛋白质来萌芽和进入(融合)。