STRUCTURAL STUDIES OF VIRAL POLYMERASES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这两种晶体，流感病毒NP和DXV VP1，已经在我们的实验室使用内部x射线衍射设备进行了测试。由于这些晶体的尺寸相对较小，它们的衍射分辨率仅为~4埃。因此，迫切需要同步辐射来更好地收集数据和确定结构。我们将使用Se-MAD来确定相位，因此我们希望在尽可能早的日期获得F2站的波束时间。我的实验室主要研究流感病毒和乙肝病毒病毒蛋白的结构和功能。我之前在史蒂夫·哈里森博士的实验室做博士后以及在迈克尔·罗斯曼博士的实验室做研究生的时候都是研究病毒蛋白质和酶。作为独立研究者和博士后或研究生，我已经访问国际象棋十多次了。我完全理解MacCHESS在过去和未来的病毒结构确定中不可或缺的作用。流感病毒核蛋白（NP）封装病毒基因组RNA形成核糖核蛋白（RNP）复合物。功能研究表明，NP不仅是一种结构rna结合蛋白，还在介导病毒基因组rna的转录、复制和细胞内转运中发挥重要作用。我们的长期目标是阐明NP如何介导RNP的形成以及NP- rna相互作用如何调节病毒基因组复制。非常感谢您对这个建议的考虑！

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Both crystals, influenza virus NP and DXV VP1, have been tested in our laboratory using the in-house X-ray diffraction facility. Due to the relative small sizes of these crystals, they only diffracted to ~4 angstrom resolution. Therefore, synchrotron radiation is urgently needed for better data collection and structure determination. We will use Se-MAD to determine the phases, and therefore we would like to obtain some beamtime at the F2 station at the most earliest possible dates. My laboratory focuses on studying the structure and function of viral proteins from influenza viruses and birnaviruses. My previous work in Dr. Steve Harrison's laboratory as postdoc as well in Dr. Michael Rossmann's laboratory as graduate student had also been focused on viral proteins and enzymes. I have already visited CHESS more than ten times both as an independent investigator as well as a postdoc or graduate student. I fully appreiciate the indispensible role of MacCHESS in virus structure determination both in the past as well in the future. Influenza virus nucleoprotein (NP) encapsidates the viral genomic RNA to form a ribonucleoprotein (RNP) complex. Much more than a structural RNA-binding protein, functional studies have shown that NP has important roles in mediating the transcription, replication and intracellular trafficking of the virus genomic RNPs. Our long term goal is to elucidate how NP mediates the formation of RNP and how NP-RNA interaction regulates viral genome replication. Your favorite consideration of the proposal is greatly appreciated!