Mechanisms Of Rapid Memory CD8+ T-cell Inactivation
Funder
National Health and Medical Research Council
Funding Amount
$318,517.00
Summary
Type 1 diabetes (T1D) and other autoimmune diseases results from misdirected immune responses that destroy normal body tissues. The ultimate goal of therapeutic strategies is to remove or inactivate the immune cells that attack normal tissues, while leaving other immune cells, for example, those required for protection from infectious diseases and tumours, unaffected. Here we propose to test a new way of turning off inappropriate immune reactions.
Antigen-presenting cells control immune responses. Different types of these cells do different jobs and affect different diseases. We wish to control these processes by determining how the cells live and die. In particular we are interested in controlling the local immune responses during rejection of islet transplantation, which can cure type 1 diabetes.
The Mezzanine T Cell Response: Intervening At The Coal Face
Funder
National Health and Medical Research Council
Funding Amount
$765,585.00
Summary
In an initial immune response, specialised cells in lymph nodes tell T cells to multiply; the stimulated T cells depart and enter target tissue (e.g. lung in the case of flu). We describe a new response whereby the target tissue itself can tell T cells to multiply further. This response in target tissues reveals a new way of altering immune responses. This is especially important as in many diseases, the primary lymph node response has already occurred, so cannot be therapeutically intervened.
Transcriptional Regulation Of Specialized Subsets Of Dendritic Cells In Control Of Infection
Funder
National Health and Medical Research Council
Funding Amount
$616,912.00
Summary
Immune protection against viruses and bacteria depends on specialized cells called dendritic cells that display components of the invading organisms on their surface. There are multiple different types of dendritic cell and each population plays a specialized role in defending the body against infection. Our work will provide the framework for directly targeting these cells for novel vaccines to re-program the immune system for clinical conditions such as cancer, allergy and autoimmunity.
Reversing Autoimmune Diabetes By Controlling Pathogenic Effector T-cells
Funder
National Health and Medical Research Council
Funding Amount
$408,662.00
Summary
Type 1 diabetes (T1D) results from misdirected immune responses that destroy insulin-producing pancreatic cells. The ultimate goal of therapeutic strategies is to remove or inactivate the cells that attack insulin-producing cells, while leaving other cells, for example, those required for protection from infectious diseases and tumours, unaffected. Here we propose to test a new way of turning off the inappropriate immune reaction with the goal of preventing type 1 diabetes.
Immune Imprinting By Nanoparticles And Vaccines: New Principles And Translation Into The Clinic
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
Vaccines require adjuvants to be effective. Despite decades of research there is only one adjuvant approved for broad use in humans. Based on our prior findings I will engage new principles in nanotechnology, and deepen understanding of immune imprinting in various organs of the body including the lung, to develop 2nd generation broadly useful nanoadjuvants able to effectively treat cancer and malaria.
Understanding The Complexity Of Antigen Presentation
Funder
National Health and Medical Research Council
Funding Amount
$774,540.00
Summary
I have developed and established the use of mass spectrometry to identify and quantitate ligands of antigen presenting molecules to understand the breadth of immune responses in a variety of human disease states including autoimmunity, cancer, infection and allergy. By embedding the technology in disease focussed research programs I will define the molecular bases of these diseases and the important immunological targets that will provide new avenues for therapeutic development and vaccines.
Cancer immunotherapy by “checkpoint blockade” boosts the immune response and leads to tumour rejection in some patients. To improve immunotherapy, information will be sought on the capacity of membrane vesicles prepared from dendritic cells (DC) to stimulate immune cells (T cells) in mice and elicit tumour rejection. Experiments are proposed to trace the fate of the vesicles after injection and improve tumour rejection by combination with checkpoint blockade and addition of cytokines.
MAIT cells are a recently discovered type of lymphocyte that plays a unique and important role in the immune system. However, these cells vary widely in number between healthy individuals, for reasons that are unclear. This project is designed to understand the factors that control the development of MAIT cells as a step toward regulating their numbers and activity.