The aim of this proposal is to identify and characterize novel long noncoding RNAs (lncRNAs) that function to control inflammation and viability in macrophages. Macrophages are critical effector cells of the innate immune system where they function to control infection and maintain tissue homeostasis.
In Aim 1 we will perform an unbiased screen to knockdown all lncRNAs in human or murine macrophages using CRISPRi technology and determine those that function to control NF?B, the master regulator of inflammatory genes.
In Aim 2 of this proposal we will identify all lncRNAs required for macrophage viability in humans and mice. We will determine the mechanism of actions of our top conserved candidates. This proposal will allow for rapid meaningful data on the role that lncRNAs play in macrophage biology to be obtained in a highly efficient manner.
In this proposal we will carry out a high throughput unbiased screen to identify long noncoding RNAs (lncRNAs) that function to control inflammation and macrophage viability. We have generated an NF-?B reporter line in human and murine macrophages which will enable us to study the role for lncRNAs in controlling NF-?B across species. We will characterize those genes that are critical regulators of macrophage viability and function.