Our research is focussed on understanding a critical process for our health: how the immune system distinguishes self from non-self. As part of a network of interdisciplinary collaborators, we aim to reveal how the normal checkpoints for self-nonself discrimination break down in the hundred different autoimmune diseases, including Type 1 diabetes, Rheumatoid arthritis, and Sjogren’s syndrome; in the diverse range of allergic and immune deficiency diseases; and in cancer of the immune system, such as lymphomas and leukemias. Circumventing the normal process for immunological self-tolerance with new drugs that act as “self-tolerance checkpoint inhibitors” has also emerged as a third pillar of cancer treatment.
We are establishing a collaborative Consortium for Immune Disease Genomics focussed on illuminating the genetic contribution and molecular pathways at the root of human immunological diseases. This will bring together all the experience in genomic, molecular and cellular analysis of immunological disorders we have built up over the last 25 years, and connect it with the broad range of complementary clinical and laboratory expertise needed to come to grips with human immune disorders.
It leverages the discovery pathway we have successfully pioneered in mice – large-scale genome sequencing to identify molecular defects that explain immune disease – and takes it to the logical next step: analysing the genome of people with immune disease as the starting point to explain their disease and treat it at the root cause.
Two technology advances, low-cost whole genome sequencing and CRISPR/Cas9 genome editing, have opened up this new route to cut through the immunological complexity of clinical disease to identify causal genes, molecules and cellular mechanisms, and we work closely with the leaders in these technologies at Garvan and around the world.