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How do long noncoding RNAs (lncRNAs) regulate dendritic cell function and prevent autoimmune disease

How do long noncoding RNAs (lncRNAs) regulate dendritic cell function and prevent autoimmune disease

PhD/Honours project

A complex network of mechanisms allows appropriate immune responses to pathogens while preventing the development of autoimmune diseases, such as type 1 diabetes and multiple sclerosis. Recent studies suggest that long noncoding RNAs (lncRNAs) are an important component of this regulatory network, but their impact upon disease pathogenesis is unclear. LncRNAs are a new class of regulatory molecules encoded in the mammalian genome. They are broadly defined as RNA molecules that are >200 nucleotides in length and perform molecular functions without encoding proteins. Current work in our lab is focused on discovering novel lncRNAs that regulate immune cell function to prevent autoimmune disease.
We have recently identified >50 putative murine lncRNAs that are differentially expressed in activated dendritic cells (DCs), which are specialised immune cells that mediate both innate and adaptive immune responses. Notably, we have shown that disrupting one of these lncRNAs in mice alters dendritic cell function and increases the incidence of autoimmune disease in different mouse models of type 1 diabetes and multiple sclerosis. Intriguingly, some of the other lncRNAs we identified in our dendritic cell screen map to human genomic regions linked to different immune-related diseases. The goal of this project is to characterise the role of these lncRNAs in different immune cells and determine how disrupting these lncRNAs affects disease pathogenesis.
This project will use a range of cellular and molecular techniques including cell-culture based assays, FACS, RNAseq, EMSA/mass spectrometry, RNA-FISH and ELISAs. In addition, we have used CRISPR/Cas9 mutagenesis to generate unique knockout cell lines and mice to further investigate the role of these lncRNAs in the development of autoimmune disease. Students will also have the opportunity to work with our collaborators in the Immunology & Diabetes Unit at St Vincent's Institute, Biomedicine Discovery Institute at Monash University, and the Walter & Eliza Hall Institute.

Supervisor: Dr Tom Brodnicki
Tel: 03 9231 2480 / Email: tbrodnicki@svi.edu.au

Supervised by:

  • Dr Tom Brodnicki
  • Disease Focus:

  • Type 1 diabetes
  • Research Unit:

  • Immunogenetics