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.
