April 1, 2024
Project Support: KAKENHI Grant-in-Aid for Scientific Research (B)
Related Project: lncRNAs in dendritic cell differentiation
This project aims to elucidate the roles and functional features of long noncoding RNAs (lncRNAs) in establishing and maintaining immune responses by studying infected dendritic cells type-1 (DC1).
Introduction
Dendritic cells (DCs) are antigen-presenting cells that function as the control center of immune responses. When infected with Toxoplasma gondii, or other intracellular pathogens, dendritic cells type-1 (DC1) turn on the host defense programs that allow them to prime adaptive immune T-cells to fight the infection. It has been previously shown that expression profiles of mRNAs responsible for activation of infected DC1s are established early on during differentiation through extensive chromatin remodeling and activation Kurotaki et al, PNAS, 119 (34) e2207009119, 2022. However, many details of how the functional landscape of DC1 is established and regulated remain unknown.
Concurrent recent reports have suggested the involvement of long noncoding RNAs (lncRNAs) in the regulation of pathogenic infections; reviewed in Front Cell Infect Microbiol., 13, 1160198, 2023. Nonetheless, it remains unknown how the majority of lncRNAs regulate responses to infection.
While investigating the roles of lncRNAs in regulating DC type1 (DC1) differentiation, we also sought to understand how lncRNAs can establish and maintain DC1 responses to infection. Our preliminary analyses uncovered hundreds of differentially expressed known and novel lncRNAs in DC1s infected with Toxoplasma gondii.
Fig: Chromatin structure re-arrangement and activation at gene loci related to host defense occur progressively during various stages of DC1 development (Kurotaki et. al., 2022)
Project Specific Aims
- create an atlas of lncRNAs resting and Tx-infected DC1s
- understand expression changes of lncRNAs upon infection
- understand subcellular localization changes of lncRNAs upon infection
- elucidate how lncRNAs co-function with relevant mRNAs/proteins during DC1 infection
Methods & Data
Using our multi-omics data (RNA-seq, ChIP-seq, ATAC-seq, Hi-C) and a variety of public and proprietary algorithms we are now exploring how lncRNAs function in the T. gondii infected DC1 cells.
JSPS Postdoc Needed
PhD Researchers with background in (i) Bioinformatics/AI and/or (ii) Biology (basic bioinformatics skills required) are welcome to apply for JSPS Postdoc with us!
Questions? Interested in joining us? Please email Jordan 📧