A role for long non-coding RNAs (lncRNAs) in regulating dendritic cell function and preventing autoimmune disease
A complex network of regulatory mechanisms allows appropriate immune responses to infectious pathogens while preventing self-destruction of tissues. Recent studies indicate that long noncoding RNAs (lncRNAs) are a component of this network, but their role in the development of autoimmune disease is poorly understood. LncRNAs are defined as RNA molecules >200 nucleotides in length that perform different functions without encoding proteins.
We have 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 found that disrupting one of these lncRNAs in mice alters dendritic cell function and increases the incidence of autoimmune disease in mouse models of type 1 diabetes and multiple sclerosis.
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 assays, FACS, RNAseq, EMSA/mass spectrometry, RNA-FISH and ELISAs. In addition, we will use CRISPR/Cas9 gene editing to generate unique knockout cell lines and mice to further investigate the role of these lncRNAs in the development of autoimmune disease. Co-supervised by Associate Professor Meredith O'Keeffe from Monash University.
*In addition to SVI Top-Up Scholarships, students working on this project may be eligible for top-up awards from the Australian Juvenile Diabetes Research Foundation.
Dr Tom Brodnicki
Type 1 diabetes
Our group investigates how certain genes affect immune cell responses that are important for preventing autoimmune and infectious diseases. Studying such genes in humans is difficult due to genetic heterogeneity and tissue availability. Our strategy is to take advantage of different mouse models to discover disease susceptibility genes. We employ a combination of gene editing techniques and transcript profiling, along with immune cell assays and protein functional studies. Our ongoing work has identified unsuspected genes and unique molecular mechanisms that regulate destructive immune responses and prevent disease pathology. Our ultimate goal is to turn these findings into new therapeutic targets for treating autoimmune and infectious diseases.
For further information about this project, contact: