Genetic Analysis of TLR Signaling and Innate Resistance to Viral Infection

TLR 信号传导和病毒感染先天抵抗力的遗传分析

• 批准号: 10240688
• 负责人: BRUCE A BEUTLER
• 金额: $ 54.14万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10240688
• 关键词: Adaptor Signaling Protein; Affect; Alleles; Antiviral Response; Archives; Cellular biology; Collaborations; Defect; Ethylnitrosourea; Exercise; Gene Proteins; Genes; Genetic; Genome; Genotype; Grant; Immune signaling; Immunity; Inflammation; Interferons; Laboratories; Mediating; Mus; Mutagenesis; Mutant Strains Mice; Mutation; Process; Production; Proteins; Resistance; Signal Transduction; System; TNF gene; Time; Virus Diseases; Work; biochemical tools; genetic analysis; genetic approach; macrophage; mutant; screening

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.

项目摘要 我们已经开发并应用了一个高度自动化的系统，随机生殖系诱变探针TLR 信号传导和抵抗病毒感染。寻找更多参与TLR信号传导的蛋白质 将继续因为我们还没有接近基因组的饱和。此外，我们还发现了一些 在这些过程中具有重要功能的基因，并建议进一步研究它们。作为新的和必要的 系统的组成部分被确定，我们将寻求理解他们的机械使用的工具， 生物化学、细胞生物学和遗传学。我们还将分析MyD88与 Ticam 1通过将由每个衔接蛋白行使的抑制影响的特异性标记物置于 监视我们设想与西雅图、斯坦福大学、拉霍亚和悉尼的同事密切合作， 我们已经工作了很多年。