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

基本信息

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
项目类别：
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

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

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项目摘要

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随机种系诱变系统，以探测TLR 小鼠病毒感染的信号传导和抗性。寻找参与TLR信号的更多蛋白质的搜索由于我们尚未接近基因组的饱和，将继续进行。而且，我们已经确定了一个数字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。作为新的和必不可少的确定了系统的组件，我们将寻求使用机械理解它们的工具生物化学，细胞生物学和遗传学。我们还将分析MyD88和 TICAM1通过放置每个衔接蛋白在下面行使的抑制作用的特定标记监视。我们设想与西雅图，斯坦福，拉霍亚和悉尼的同事与我们的同事们进行密切合作我们工作了很多年。