Summary
This research project aims to define the role of nuclear paraspeckles, formed on lncRNA Neat1, in regulating the timing and amplitude of innate immune gene expression in macrophages, which is critical for a balanced immune response.
Defining the role of lncRNA Neat1 and the nuclear paraspeckle in regulating macrophage innate immune gene expresison
US · IL
NIH
grant
open
#nih-1F31AI197784-01
What they want
The project will investigate how macrophage paraspeckles are dynamically regulated in response to various cellular stresses and how their composition changes, particularly following lipopolysaccharide (LPS) treatment. The central hypothesis is that paraspeckles control innate immune gene expression by dynamically sequestering and releasing nuclear proteins/RNA binding proteins. Aim 1 will define paraspeckle dynamics using a high-throughput screen with GFP-tagged macrophage cell lines. Aim 2 will compositionally define the paraspeckle over an LPS time course using the O-MAP biotin proximity labeling approach and explore how novel paraspeckle-associated proteins contribute to macrophage antimicrobial responses.
Deliverables
- Definition of macrophage paraspeckle dynamics in response to various cellular stresses
- Compositional definition of the paraspeckle over a time course of LPS treatment
- Insights into how novel paraspeckle-associated proteins contribute to macrophage antimicrobial responses
- Understanding of how cellular stresses control paraspeckle dynamics and how protein reorganization within paraspeckles controls innate immune gene expression in macrophages
Technical requirements
- High-throughput screen using macrophage cell lines that express GFP-tagged paraspeckles
- Biotin proximity labeling approach (O-MAP)
