High throughput functional characterization of lncRNAs in macrophage biology

Project Summary
In this proposal we combine a number of technological approaches to provide a novel way
to functionally characterize complex gene networks to identify those that function to
regulate biological processes in macrophages.
Advances in deep sequencing technologies have revealed that the majority of the human
genome is actively transcribed into RNA. Our lab is focused on characterizing the largest
group of RNA produced from the genome named long noncoding RNA (lncRNAs) and
their associated protein binding partners. To date only 3% of lncRNAs have been
functionally validated. This project is highly innovative as we will perform the first
systematic unbiased screens and create the first genetic interaction maps to identify
functionally relevant lncRNAs involved in viability and functions within macrophages.
Using our newly developed reporter cell lines in both human and mouse we will be able to
rapidly screen and map for lncRNAs and their protein binding partners that are critical for
controlling viability and inflammatory signaling. We will also obtain crucial information on
functional conservation of lncRNAs across species. We will then create genetic mouse
models to prove the importance of these genes and their regulatory networks in controlling
immune responses during sepsis in vivo. This approach will allow for rapid meaningful
data to be obtained in a highly efficient manner. Accomplishing the ambitious goals of this
proposal will provide us with a wealth of information on the complex pathways involving
lncRNAs and gain insights into their roles in contributing to viability and functions of
macrophages.

Grant Number: 5R35GM137801-05
NIH Institute/Center: NIH
Principal Investigator: Susan Carpenter