The immune system is the essential complex barrier that protects the organism for infections and some malignancies. Despite considerable efforts, the mechanism by which immune cells kill dangerous unwanted cells is poorly understood. This project will investigate the mechanism of action and the role in human pathologies of a key component of the immune system, a toxic protein perforin.
Perforinopathy: Immune-disease Due To Defective Perforin Function
Funder
National Health and Medical Research Council
Funding Amount
$671,514.00
Summary
White blood cells called cytotoxic lymphocytes destroy cancerous cells using special toxic molecules. One of them, perforin, eliminates dangerous cells by punching holes in their membrane. Some individuals that lack perforin become seriously ill in their infancy. Others, that retain some perforin in their lymphocytes can live longer and are at higher risk of developing cancer. We will investigate the causes of partial loss of perforin function and explore novel drug therapies, which should addre ....White blood cells called cytotoxic lymphocytes destroy cancerous cells using special toxic molecules. One of them, perforin, eliminates dangerous cells by punching holes in their membrane. Some individuals that lack perforin become seriously ill in their infancy. Others, that retain some perforin in their lymphocytes can live longer and are at higher risk of developing cancer. We will investigate the causes of partial loss of perforin function and explore novel drug therapies, which should address the problem and restore immune function.Read moreRead less
Regulation Of Natural Killer Cell Homeostasis By Multiple Components Of The Immune System
Funder
National Health and Medical Research Council
Funding Amount
$327,151.00
Summary
Differentiation and homeostasis of immune cell populations such as CD4 and CD8 T cells and dendritic cells has been key to understanding their function during inflammation. In contrast, late stage natural killer (NK) cell differentiation has largely been ignored. Given the key role of NK cells in providing innate effector immunity and shaping adaptive responses, a better understanding of the cues that regulate their differentiation is clearly warranted.
NK Cells As The Missing Link Between Anti-cancer Chemotherapy And CD8 T Cell Responses
Funder
National Health and Medical Research Council
Funding Amount
$488,478.00
Summary
Cytotoxic chemotherapy is the standard of care for most tumors but it rarely cures. The immune system has the capacity to destroy malignant cells but tumors usually evade immune destruction. Combination of chemo- immunotherapy may change this. DNA damage in tumor cells, caused by chemotherapy, induces expression of a set of molecules that activate Natural Killer cells. These cells can then activate anti-tumor T cells. Therapies that enhance this pathway may induce sustained anti-tumor effects.