NSF/MCB-BSF: RNA-mediated regulation of innate immunity

NSF/MCB-BSF：RNA 介导的先天免疫调节

• 批准号: 1917050
• 负责人: Heather Hundley
• 金额: $ 83.83万
• 依托单位: Indiana University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1917050&HistoricalAwards=false
• 关键词: NSF; MCB; BSF; RNA; mediated

This project will address how organisms maintain a precise balance of molecules that fight infection. Some such molecules accumulate in various organisms even in the absence of a threat, so that the organism is ready to fight a pathogen immediately upon infection. However, production of excessive amounts of these molecules has been shown to inhibit growth in plants, cause tissue damage in animals and autoimmune disease in humans. The objective of this project is to understand how the optimal amount of infection-fighting molecules is maintained in a model organism Caenorhabditis elegans, by dissecting the antagonistic role of the ADAR family of RNA binding proteins and small RNA silencing factors in regulating the expression of these molecules. This research will involve direct participation by graduate and undergraduate students, including underrepresented minorities and first-generation college students. Additional undergraduate and graduate students together with the US PI will participate in hands-on science lessons to kindergarten students. In an effort to broaden participation of underrepresented groups, the US PI will continue to serve as a faculty mentor for a residential community of female STEM undergraduates and will provide a workshop to incoming graduate students to help students navigate the path to successful completion of a doctoral degree.The mechanisms by which the nervous system influences the immune response has recently become an area of intense investigation. While many efforts are aimed at understanding how neuro-immune communication is involved in induction of the immune response, this project focuses on an underexplored area regarding how gene expression in the nervous system contributes to basal immunity. This research seeks to answer three fundamental questions 1) Can expression of an RNA binding protein specifically within neural cells influence pathogen susceptibility? 2) Does RNA editing contribute to innate immunity? 3) What small RNA pathways affect resistance to pathogens? To tackle these questions, the collaborative research will leverage the strengths of the US PI (gene regulation by ADARs, biochemistry) and the Israeli investigator (small RNAs, computational biology). These studies will fundamentally advance our understanding of RNA-mediated regulation of innate immunity as well as provide further insight into how the nervous and immune systems communicate. Furthermore, as small RNAs and RNA binding proteins are major regulators of post-transcriptional gene regulation, these studies will provide a paradigm for how antagonism between these factors can fine-tune gene expression.This collaborative US/Israel project is supported by the US National Science Foundation and the Israeli Binational Science Foundation.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该项目将解决生物体如何保持分子的精确平衡来对抗感染。一些这样的分子即使在没有威胁的情况下也会在各种生物体中积累，因此生物体在感染后立即准备好对抗病原体。然而，过量的这些分子的产生已被证明会抑制植物的生长，导致动物的组织损伤和人类的自身免疫性疾病。本项目的目的是了解如何在模式生物秀丽隐杆线虫中维持最佳数量的抗感染分子，通过解剖RNA结合蛋白和小RNA沉默因子的阿达尔家族在调节这些分子表达中的拮抗作用。这项研究将涉及研究生和本科生的直接参与，包括代表性不足的少数民族和第一代大学生。其他本科生和研究生以及美国PI将参加幼儿园学生的动手科学课。 为了扩大代表性不足的群体的参与，美国PI将继续担任STEM女本科生住宅社区的教师导师，并将为即将入学的研究生提供研讨会，以帮助学生顺利完成博士学位。神经系统影响免疫反应的机制最近成为一个深入研究的领域。虽然许多努力的目的是了解神经免疫通讯是如何参与诱导免疫反应，这个项目的重点是一个未充分探索的领域，关于神经系统中的基因表达如何有助于基础免疫。这项研究试图回答三个基本问题：1）神经细胞内RNA结合蛋白的表达是否会影响病原体的易感性？2)RNA编辑有助于先天免疫吗？3)哪些小RNA途径影响对病原体的抵抗力？为了解决这些问题，合作研究将利用美国PI（ADAR基因调控，生物化学）和以色列研究人员（小RNA，计算生物学）的优势。这些研究将从根本上推进我们对RNA介导的先天免疫调节的理解，并进一步了解神经和免疫系统如何沟通。此外，由于小RNA和RNA结合蛋白是转录后基因调控的主要调节因子，这些研究将为这些因素之间的拮抗作用如何微调基因表达提供一个范例。以色列项目由美国国家科学基金会和以色列两国科学基金会支持。该奖项反映了NSF的法定使命，并通过使用基金会的学术价值和更广泛的影响审查标准。