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

这个项目将解决生物体如何维持抗击感染的分子的精确平衡。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，从而使生物体在感染后立即准备好与病原体作战。然而，过量的这些分子的产生已被证明抑制植物的生长，导致动物的组织损伤和人类的自身免疫性疾病。本项目的目的是通过剖析ADAR家族的RNA结合蛋白和小RNA沉默因子在调节抗感染分子表达中的拮抗作用，了解如何在模式生物秀丽线虫中维持最适量的抗感染分子。这项研究将由研究生和本科生直接参与，包括未被充分代表的少数民族和第一代大学生。更多的本科生和研究生将与美国PI一起参加幼儿园学生的实践科学课程。为了扩大代表不足的群体的参与，美国PI将继续担任STEM女本科生住宿社区的教师导师，并将为即将入学的研究生提供研讨会，帮助学生顺利完成博士学位的学习。神经系统影响免疫反应的机制最近已成为一个紧张的研究领域。虽然许多努力的目的是了解神经免疫通讯如何参与免疫反应的诱导，但该项目专注于一个未被探索的领域，即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)神经细胞中特定的RNA结合蛋白的表达是否会影响病原体的易感性？2)RNA编辑是否有助于天然免疫？3)哪些小的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的基因调控，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促进我们对RNA介导的天然免疫调节的理解，并为神经和免疫系统如何沟通提供进一步的见解。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者，这些研究将为这些因素之间的对抗如何微调基因表达提供一个范例。这一美国/以色列合作项目得到了美国国家科学基金会和以色列双国科学基金会的支持。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.