Inflammasome Sensors And Immune Protection Against Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$750,110.00
Summary
Intestinal cancer is a leading cause of death in Australia and worldwide. Defects in the immune system can lead to the development of intestinal cancer. In this project, we will investigate the critical role of an immune sensor in inhibiting the development of intestinal cancer. This project will provide new insights into the interplay between the immune system and cancer biology and will potentially inform the development of new immunotherapies.
Cells recycle old components using a system called the proteasome. Some people are born without parts of the proteasome, and they suffer from a disease associated with inflammation. We have identified the molecular trigger for this inflammation. Our findings are also relevant for patients being treated with proteasome inhibitors. In some of these diseases, such as lupus, inflammation can be a side-effect of proteasome inhibitor therapy, and we can now reduce this and make the treatments safer.
Amyotrophic Lateral Sclerosis (ALS) is a progressively fatal neurodegenerative disease characterized by aggregates of a protein called TDP-43. ALS also features the presence of several inflammatory cytokines in the central nervous system. In this project, we will study how TDP-43 abnormally mislocalizes within cells, releasing mitochondrial DNA and triggering a novel pathway of inflammation. We propose that targeting this pathway could lead to new treatments for ALS.