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.
Interleukin-1β Biology: Mechanisms Of Regulation, Activation And Secretion
Funder
National Health and Medical Research Council
Funding Amount
$641,979.00
Summary
The protein called intelreukin-1 (IL-1) is required to fight off invading pathogens but more recently has been implicated as contributing to diverse diseases characterised by excessive inflammation, such as arthritis, gout, atherosclerosis and even cancer. This project aims to understand how IL-1 is made within cells and then activated to cause inflammation, which will enable these processes to be therapeutically targeted.
Testing A Combination Of 2 Clinical Drugs, An IAP Inhibitor And P38 Inhibitor, To Treat AML
Funder
National Health and Medical Research Council
Funding Amount
$200,890.00
Summary
Current treatments only cure 50% of Acute Myeloid Leukaemia (AML) patients, and novel approaches to treatment are desperately needed to improve survival of patients with leukaemia. One new drug, Birinapant, is currently being tested in clinical trials to treat AML. I have found that some AMLs are resistant to Birinapant treatment but the addition of a second drug (called “p38 inhibitors”) can now overcome this resistance. I will test how effective combining these two drugs can be to treat AML.
Regulation Of Interleukin-1? Activation In Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$624,429.00
Summary
IL-1? protein is required to combat infection but also contributes to inflammatory diseases, such as Rheumatoid arthritis and diabetes. Understanding how IL-1? is produced is therefore critical to the development of better therapeutics for these conditions. We have identified a new pathway involving the protein RIP3 that can cause IL-1? activation. This project will examine how this pathway is molecularly regulated and determine its importance in inflammatory disease models.
Mapping The TNF Pathway: A Qualitative And Quantative Molecular Analysis Of The Components And Post-translational Modifications Involved In Physiological And Pathological TNFR1 Signalling
Funder
National Health and Medical Research Council
Funding Amount
$636,258.00
Summary
TNF is a master regulator of the inflammation response and dysregulated TNF signalling causes many human diseases. We will use a cutting edge mass spectrometry technique that we have developed to analyse molecules required for TNF signalling. Understanding how the TNF signalling works in all cell types and with different forms of ligands will open up therapeutic opportunities to selectively target TNF signalling in inflammatory diseases, such as Rheumatoid Arthritis and Cancer.
Understanding The Role Of The Atypical Cadherin Fat4 In Lymphatic Vascular Development
Funder
National Health and Medical Research Council
Funding Amount
$1,006,248.00
Summary
This application will define the role of a large cell adhesion molecule, FAT4, in lymphatic vascular development. By understanding how FAT4 functions in lymphatic vessels, we will gain insight to the mechanisms by which mutations in the gene that encodes this protein cause a human lymphoedema syndrome.
T cells play a central role in the immune response. The primary event in T cell activation is the triggering of a specific T cell receptor (TCR). Our studies will define new mechanisms for the regulation of TCR-mediated T cell responses. Our studies may yield novel insight into processes that contribute to the development of type 1 diabetes & inflammatory bowel disease.
Targetting The CIB1-sphingosine Kinase Interaction In Oncogenesis
Funder
National Health and Medical Research Council
Funding Amount
$805,034.00
Summary
Sphingosine kinase is a protein involved in cancer development and progression. We have identified that the cancer-inducing activity of sphingosine kinase is controlled by another protein called CIB1 which itself appears involved in causing cancer by deregulating sphingosine kinase. In this study we will examine and target the interaction between sphingosine kinase and CIB1 as a potential therapeutic intervention in cancer.
Cells are building blocks of living things and require signalling pathways to communicate their functions. We discovered a new signalling pathway in flies that remarkably exists in yeast and plants to more complex organisms like mice and man. We will study this new signalling pathway in flies to find out how and why it communicates in cells. As flies and humans share similar genes, our studies will inform how this previously unknown signalling pathway functions from simple to complex organisms
Do Synaptic-like Mechanisms Control Insulin Secretion?
Funder
National Health and Medical Research Council
Funding Amount
$593,235.00
Summary
An estimated 415 million people world-wide were diagnosed with diabetes in 2015. One of the causal factors in disease is the dysregulation of insulin secretion. We have developed new techniques to study insulin secretion that has led us to propose a new model for secretory control. This proposal sets out experiments to critically test this model. The outcomes could have wide-reaching impact on understanding and for future treatment and prevention of the diabetes.