Only recently has it emerged that our cells have a built-in backup mechanism that instructs cells to die in extreme cases, such as when viruses have hijacked a cell. A misfiring backup mechanism is thought to underlie a number of human diseases, including inflammatory disease. Our investigation will establish a starting point for the development of novel anti-inflammatory drugs.
Platelets are key blood elements that are essential for the prevention of bleeding in response to injury or infection. Overactive or spontaneously active platelets cause thrombosis and blood clot formation. My laboratory has identified new physiological pathways of activation of platelet metalloproteinases, the enzymes that regulate surface levels of the prothrombotic platelet receptors. By understanding this mechanism of receptor regulation, we can uniquely target platelet receptors in people w ....Platelets are key blood elements that are essential for the prevention of bleeding in response to injury or infection. Overactive or spontaneously active platelets cause thrombosis and blood clot formation. My laboratory has identified new physiological pathways of activation of platelet metalloproteinases, the enzymes that regulate surface levels of the prothrombotic platelet receptors. By understanding this mechanism of receptor regulation, we can uniquely target platelet receptors in people with prothrombotic pathologies.Read moreRead less
Genomic Analysis Of DNA Binding And Gene Regulation By The Chromatin Remodelling Factor UBF
Funder
National Health and Medical Research Council
Funding Amount
$624,254.00
Summary
Synthesis of ribosomes, the cellular protein synthetic machinery, is the major anabolic event of a growing cell and is frequently dysregulated during disease such as cancer. This grant will examine a protein termed UBF that we think plays an important role in orchestrating the cellular response to dysregulated ribosome biogenesis. By understanding how UBF functions we hope to uncover novel therapeutic approaches to treat diseases associated with ribosome stress .
Investigating B Cell Development, Maintenance And High-affinity Antibody Production By ENU Mutagenesis
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
B cells are essential for the protection against infections. This application aims to identify new genes that are crucial for the development or function of B cells and will investigate how mutations in newly discovered genes contribute to defects in the development and function of B cells and the pathogenesis of B cell leukaemia.
How Does NF-kB2 Regulate Thymic Selection To Prevent Organ-specific Autoimmune Disease?
Funder
National Health and Medical Research Council
Funding Amount
$787,600.00
Summary
Autoimmune diseases like type 1 diabetes and thyroiditis arise from defects that cause the immune system to confuse self and non-self. Normally, this distinction is programmed in the thymus. We recently identified the gene that causes a form of autoimmune disease. We also made an important discovery about how the thymus gland regulates self-non-self discrimination. We will build on these two discoveries to gain a precise understanding of how the immune system normally avoids autoimmune disease.
Investigating The Cellular Response To Iron-Depletion: The Trilogy Of ASK1, Thioredoxin And Ribonucleotide Reductase
Funder
National Health and Medical Research Council
Funding Amount
$552,572.00
Summary
Iron is crucial for many essential biological processes. Recently, we demonstrated that iron-depletion can affects important signalling pathways (e.g., JNK and p38) that play important roles in growth arrest and apoptosis. This study is designed to investigate the cellular and molecular effects of iron depletion which currently remains unclear. The research is crucial for understanding: (1) the effects of iron deficiency and (2) for understanding the effects of iron chelators that are used for t ....Iron is crucial for many essential biological processes. Recently, we demonstrated that iron-depletion can affects important signalling pathways (e.g., JNK and p38) that play important roles in growth arrest and apoptosis. This study is designed to investigate the cellular and molecular effects of iron depletion which currently remains unclear. The research is crucial for understanding: (1) the effects of iron deficiency and (2) for understanding the effects of iron chelators that are used for treating various diseases.Read moreRead less
Epigenetic Regulation By PKC-theta In Human Breast Cancer Stem Cells.
Funder
National Health and Medical Research Council
Funding Amount
$818,132.00
Summary
Treating women with advanced breast cancer is difficult, and new drugs are needed to kill the cancer stem cells that cause recurrence. We think that a newly discovered protein, PKC-?, plays an important role in recurring breast cancer and can be targeted using novel ‘epigenetic’ drugs. Here, we will use cutting-edge DNA techniques to learn how this protein controls how cancer cells grow and produce the necessary data to show that targeting this protein is likely to be effective in real patients.
Understanding The Role Of The Putative Phospholipid Translocase ATP11c In B Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$455,153.00
Summary
The immune system protects humans against recurrent infections with a wide range of pathogens. Formation of antibodies is a crucial element of the immune response. Defects in the production of antibodies can lead to recurrent and often life-threatening infections. This project seeks to understand a genetic defect in mice resulting in an almost complete absence of antibody producing cells, thereby causing a disease that is similar to some forms of human immunodeficiency.
Humanisation And Pre-clinical Validation Of A Therapeutic Anti-cancer Antibody
Funder
National Health and Medical Research Council
Funding Amount
$699,136.00
Summary
This grant will develop a novel antibody against a protease expressed on cancer cells. Preclinical studies, and antibody humanisation, will be performed. This project will also provide vital information on optimal therapeutic approaches with the antibody that can be ultimately taken into human trials.