COBRE: NDSU: PROJECT 5: NEW INVESTIGATOR

COBRE：NDSU：项目 5：新调查员

• 批准号: 8167865
• 负责人: Sangita Sinha
• 金额: $ 11.23万
• 依托单位: NORTH DAKOTA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167865
• 关键词: Autophagocytosis; Biochemical; Centers of Research Excellence; Computer Retrieval of Information on Scientific Projects Database; Data; Degradation Pathway; Funding; Goals; Grant; Homologous Gene; Immune; Institution; Investigation; Laboratories; Mediator of activation protein; Molecular; Natural Immunity; Pathway interactions; Protein Inhibition; Proteins; Reagent; Recombinant Proteins; Research; Research Personnel; Resources; Role; Signal Transduction; Source; Structure; Techniques; United States National Institutes of Health; Viral; Work; base; overexpression; pathogen; protein function

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. Section A: Specific Aims The ultimate goal of research in my laboratory is to use various structural and biochemical techniques to understand the atomic basis of function of proteins of pathways like autophagy (a lysosomal targeting pathway for degradation of intracellular objects) and innate immune pathway; the cross-talk between these pathways; the role of these pathways/proteins in the defense against pathogens; and the inhibition of these proteins by different pathogens. One project focuses on investigating the structure, function and molecular mechanism of Beclin1, an essential autophagy effector. Our previous work, funded in part by an NIH R21 grant, investigated the molecular mechanism by which cellular and viral Bcl-2 proteins inhibit Beclin 1 and autophagy. We plan to continue our investigation of the Beclin 1 protein, including its interaction with other autophagy proteins and with pathogen-encoded proteins. Another project focuses on Rig-I, a key mediator of anti-viral innate immunity. We plan to investigate the atomic basis of the role of Rig-I in innate defenses by studying the intra-molecular, intra- pathway or cross-pathway interactions of the Rig-I CARD domains that transmit signals to trigger or repress various pathways. A prerequisite of all these studies is the availability of pure, homogeneous, recombinant protein. We are using COBRE funding to produce these reagents and obtain preliminary data to apply for other grants to further investigate these pathways. Specific aims of the COBRE funding are to overexpress and purify the recombinant proteins listed below, in quantities suitable for subsequent structural and biochemical studies: + Aim 1: Different Beclin 1 domains. + Aim 2: Rig-I CARD domains. + Aim 3: CARD domains of IPS-1, its downstream signaling partner. + Aim 4: Repressor domains of Rig-I and LGP2 (a Rig-I homolog). + Aim 5: The essential autophagy effector Atg5, which interacts with the Rig-I and IPS-1 CARD domains.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 A节：具体目的 在我的实验室中研究的最终目标是使用各种结构和生化 了解自噬等途径蛋白质功能的原子基础 （溶酶体靶向途径，用于降解细胞内物体）和先天免疫 途径；这些途径之间的串扰；这些途径/蛋白质在 防御病原体；以及不同病原体对这些蛋白质的抑制作用。 一 项目着重研究Beclin1的结构，功能和分子机制， 必不可少的自噬效应子。 我们以前的工作，部分由NIH R21赠款资助， 研究了细胞和病毒Bcl-2蛋白的分子机制 1和自噬。 我们计划继续研究Beclin 1蛋白，包括 与其他自噬蛋白和病原体编码蛋白的相互作用。 其他 项目侧重于Rig-I，这是抗病毒先天免疫的关键调解人。 我们计划调查 RIG-1在先天防御中的作用的原子基础，通过研究种子内，内部 - 将信号传输到的RIG-I卡域的途径或跨道路相互作用 触发或压制各种途径。 所有这些研究的先决条件是纯，同质，重组的可用性 蛋白质。 我们正在使用毛茸茸的资金生产这些试剂并获得初步数据 申请其他赠款以进一步研究这些途径。 毛绒的具体目的 资金将过表达和净化下面列出的重组蛋白，数量 适用于随后的结构和生化研究： + AIM 1：不同的Beclin 1域。 + AIM 2：RIG-I卡域。 + AIM 3：IPS-1的卡域，其下游信号伴侣。 + AIM 4：RIG-I和LGP2的阻遏域（RIG-I同源物）。 + AIM 5：与RIG-I和IPS-1相互作用的基本自噬效应子ATG5 卡域。