An immune transcriptional regulatory network approach to Multiple Sclerosis (Old ID 22105)
Role
Principal Investigator
Description
Multiple Sclerosis (MS) is an autoimmune disease resulting from a complex interaction between genetic and environmental factors. In an attempt to understand the integration of both sets of risk factors, we have compared mRNA transcripts between relapsing/remitting (RR) MS patients and healthy controls in 5 leukocyte subsets: CD4 and CD8 T cells, B cells, NK cells and monocytes. A gene co-expression network was generated based on correlation of expression levels across >700 gene expression microarrays, and a major co-ordinately regulated sub-network (module) of mRNA transcripts that is differentially expressed in the monocytes of RR-MS patients was identified. This project validates, characterizes and attempts to manipulate this transcriptional module in human cells ex-vivo and in the experimental autoimmune encephalomyelitis (EAE) model of central nervous system (CNS) autoimmunity. These results should provide greater explanatory power than the analyses of individual risk factors separately and may provide a multi-faceted target for intervention.
Date
01 Jan 2016 - 31 Dec 2019
Project Type
GRANT
Keywords
Autoimmunity;Cellular Immunology;Immunogenetics;Multiple Sclerosis;mouse models;humans
Funding Body
Multiple Sclerosis Research Australia
Amount
240000
Project Team
Letitia Smith;Margaret Jordan