The Role of Rafts in Virus-Induced Membrane Remodeling

申请人简介（由申请人提供）：申请人在物理、光学、计算机方面有较强的定量背景，对研究有浓厚的兴趣。进一步接受生物医学研究方法方面的培训，特别是细胞生物学和假设驱动科学方面的培训，将使他能够研究更广泛的跨学科问题，并使他成功发展成为一名独立的生物医学研究者。培训环境包括缅因大学，私家侦探正在那里建立一个新的实验室和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，以及美国第一个4Pi显微镜的收购，有很多机会进行高度相关的生物医学研究合作，专题讨论会，研讨会，以及大学的团队资助写作。合作访问美国国立卫生研究院，导师在那里经营着一个完善的实验室，将提供极好的研究培训机会，与生物医学专家互动，并获得设备。

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).