Genetic Analysis of TLR Signaling and Innate Resistance to Viral Infection

项目摘要 我们已经开发并应用了一个高度自动化的随机胚系诱变系统来探测TLR 小鼠对病毒感染的信号和抵抗力。寻找更多参与TLR信号转导的蛋白质 将继续下去，因为我们还没有接近基因组的饱和。此外，我们已经确定了一个数字 对在这些过程中具有重要功能的基因进行研究，并建议对其进行进一步研究。作为新的和必要的 确定系统的组件后，我们将使用以下工具机械地理解它们 生物化学、细胞生物学和遗传学。我们还将分析MyD88和MyD88之间的拮抗关系 Ticam1通过将每个接头蛋白所发挥的抑制影响的特定标记置于 监视系统。我们希望与西雅图、斯坦福、拉霍亚和悉尼的同事密切合作， 他是我们工作了多年的人。

Project Summary We have developed and applied a highly automated system of random germline mutagenesis to probe TLR signaling and resistance to viral infection in mice. The search for still more proteins involved in TLR signaling will continue as we have not yet approached saturation of the genome. Moreover, we have identified a number of genes with essential functions in these processes and propose to study them further. As new and essential components of the system are identified we will seek to understand them mechanistically using tools of biochemistry, cell biology, and genetics. We will also analyze the antagonistic relationship between MyD88 and Ticam1 by placing specific markers of the inhibitory influence exercised by each adaptor protein under surveillance. We envision close collaboration with our colleagues in Seattle, Stanford, La Jolla and Sydney, with whom we have worked for many years.