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，光学和计算机方面具有强大的定量背景，并且对研究具有浓厚的兴趣。对生物医学研究方法的进一步培训，尤其是细胞生物学和假设驱动的科学，将使更广泛的跨学科问题受到攻击，并导致他作为独立生物医学研究者的成功发展。培训环境包括缅因州大学，P.I.正在建立一个新的实验室和分子生物物理学研究所。由于最新的生物物理学增长，研究所与杰克逊实验室之间的跨学科联系以及在美国收购了第一个4PI显微镜，因此有许多相关的生物医学研究合作，研讨会，研讨会，工作坊和团队赠款的机会。对NIH的合作访问，导师经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以及使用设备的互动提供绝佳的机会。 该研究计划着重于病毒感染的问题，这会导致相当大的死亡率。流感感染取决于膜融合，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，可能涉及微观膜簇称为筏。但是，目前有争议的此类域的大小，形状，机制和动力学。该项目将使用新型的，相对无创的荧光光谱法来测试通过分配或通过HA和脂质之间的直接相互作用来测试域。该项目还将确定域在毫秒和微秒的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还是动力学。由于有关筏动力学的信息缺乏，因此所提出的方法具有异常优势。结果将用于尝试更好地了解流感病毒如何能够聚集自己的蛋白质以进行发芽和进入（融合）。