Understanding Novel Drug Binding Pockets At G Protein-coupled Receptors
Funder
National Health and Medical Research Council
Funding Amount
$425,538.00
Summary
Cell-surface proteins exhibit multiple secondary binding sites for which only synthetic drugs have been identified so far. My hypothesis is that these secondary binding sites are common to most proteins because they are primarily targeted by largely yet unidentified endogenously released molecules that can modify the biology of these proteins.
I am a protein chemist-vascular biologist analysing structure, function and clinical role of platelet adhesion receptors regulating patho-physiological thrombus formation associated with thrombotic diseases such as heart attack and stroke.
Receptors And Ligands Regulating Human NK Cell Proliferation
Funder
National Health and Medical Research Council
Funding Amount
$692,040.00
Summary
A white blood cell called a Natural Killer (NK) cell is critical in the early control of viral infections and cancer. NK cells kill the diseased cells and secrete immunological hormones (cytokines) that alter how cells of the blood and immune systems respond. These functions of NK cells are markedly increased when NK cells are stimulated to divide. This project seeks to understand how NK cell proliferation is controlled. Receptors that recognise 'self' inhibit NK cell function and cell division ....A white blood cell called a Natural Killer (NK) cell is critical in the early control of viral infections and cancer. NK cells kill the diseased cells and secrete immunological hormones (cytokines) that alter how cells of the blood and immune systems respond. These functions of NK cells are markedly increased when NK cells are stimulated to divide. This project seeks to understand how NK cell proliferation is controlled. Receptors that recognise 'self' inhibit NK cell function and cell division thereby preserving self and destroying diseased cells. Yet many NK cells express both an inhibitory and activating receptor for this same 'self' protein. We will investigate what determines the outcome of this competing information. Many NK cell receptors remain to be identified and we will use a gene expression approach and monoclonal antibodies to identify these and determine how they affect NK cell proliferation. We will use molecular engineering to construct multimeric arrays of new NK cell receptors to search for the ligand molecules that they interact with on other cells. Identifying NK cell receptors and their ligands regulating NK cell proliferation and function will enable us to understand the role of these cells in health and in inflammatory diseases and cancer.Read moreRead less
Targeting Adenosine Mediated Immunosuppression To Enhance CAR T Cell Activity
Funder
National Health and Medical Research Council
Funding Amount
$633,447.00
Summary
The use of white blood cells genetically engineered to eradicate cancer cells specifically has been a major breakthrough in cancer treatment. These cells (CAR T cells) are very effective in blood cancers, but do not currently work well in other cancers. This is due to the immune suppressing nature of the cancer environment. I propose to use strategies to overcome this by genetically reprogramming the CAR T cells to be resistant to suppression by the cancer and therefore be more effective.
LRH-1 is a protein that is inappropriately present in cancers of the breast and other tissues. It causes cancer cells to divide and multiply, and therefore it is important to block its activity. There are, however, no treatments available that block LRH-1. This proposal brings together a team of researchers with broad experience. We will use high throughput technologies to identify and characterize novel LRH-1 inhibitors, and demonstrate their efficacy in reducing the growth of cancer cells.