Structural Studies of Crenarcheal Viruses

该奖项由2009年美国复苏和再投资法案(公法111-5)资助。新城疫病毒如SSV1和STIV生活在极端高温和酸性环境(温度80oC；4.0pH 1.0)，如在黄石国家公园发现的病毒。SSV1和STIV是这些病毒的最好特征之一，因此是研究的重要模式系统。对SSV1和STIV基因组的序列分析，以及来自极端高温环境的其他病毒的序列分析，无法表明大多数编码蛋白的功能。建议的研究集中在利用结构生物学来研究SSV和STIV蛋白质组的功能作用，以及在寄主生物Sulfolobus solfararicus中的相互作用。未知功能的病毒和宿主蛋白的结构将使用结晶学和核磁共振技术来确定。在许多情况下，这些研究预计会揭示出与已知功能的蛋白质在结构上的相似性，或者提出与蒙大拿州立大学的马克·杨博士合作，可以使用生化和遗传学实验来测试的功能。总之，这些研究将有助于加深对SSV和STIV生命周期的了解，以及这些病毒与其隐古宿主之间的分子相互作用。更广泛的影响：密歇根州立大学热生物学研究所(TBI)正在进行的许多工作，包括对超高温病毒的表征，正在通过外联计划向普通公众传播。目标群体包括K-12、部落学院和其他本科生机构。此外，TBI还与国家公园管理局/黄石国家公园合作，与公园内的普通公众进行接触。建议的研究与PI、Co-PI、系、大学和NSF的教育目标有很强的整合。高中、本科生、博士后和博士后将接受生物化学、结构生物学和热生物学方面的重要培训。积极鼓励代表性不足的群体，特别是妇女和美洲土著人的参与。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).Crenarchaeal viruses such as SSV1 and STIV inhabit extreme thermal and acidic environments (T 80oC; 4.0 pH 1.0) such as those found in Yellowstone National Park. SSV1 and STIV are among the best characterized of these viruses, and thus serve as important model systems for study. Sequence analyses of the SSV1 and STIV genomes, and those of other viruses from extreme thermal environments, are unable to suggest functions for most of the encoded proteins. The proposed research focuses on the use of structural biology to investigate the functional roles of the SSV and STIV proteomes, and on interactions in host organism Sulfolobus solfataricus. Structures of viral and host proteins of unknown function will be determined using crystallographic and NMR techniques. In many cases, these studies are expected to reveal structural similarity to proteins of known function, or to otherwise suggest functions that in collaboration with Dr. Mark Young, Montana State University, can be tested using biochemical and genetic experiments. Together, these studies will contribute to an increased understanding of the SSV and STIV life cycles, and the molecular interplay between these viruses and their crenarchaeal hosts. Broader Impact: Much of the ongoing work within the MSU Thermal Biology Institute (TBI) including the characterization of hyperthermophilic viruses is being communicated to the general public through outreach programs. Target groups include K-12, tribal colleges, and other undergraduate institutions. In addition, TBI partners with the National Park Service /Yellowstone National Park in outreach to the general public within the Park. There is strong integration of the proposed research with the educational goals of the PI, Co-PI, the Department, the University, and the NSF. Students at the high school, undergraduate, doctoral and post-doctoral levels will receive significant training in biochemistry, structural biology and thermal biology. The involvement of under represented groups, particularly women and Native Americans, is actively encouraged.