Role Of Sphingosine Kinase 1 In PP2A-associated Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$522,994.00
Summary
Defects in protein phosphatase 2A (PP2A) are widely associated with the development of solid tumors and leukemia. The precise mechanisms whereby defects in PP2A lead to cancer, however, remain undefined. We have recently identified that the oncogenic protein sphingosine kinase 1 (SK1) as a target of PP2A. In this study we will examine the role of SK1 in PP2A-associated cancers. Successful outcomes in these studies will establish SK1 as a target for therapeutic intervention in these cancers.
Mechanisms Of Regulation And Biological Roles Of Sphingosine Kinase 2
Funder
National Health and Medical Research Council
Funding Amount
$517,989.00
Summary
We have identified that a protein called sphingosine kinase 2 (SK2) is a potential target for anti-cancer therapies. Our preliminary studies indicate that phosphorylation of SK2 controls its function. In this proposal we will define how phosphorylation alters SK2 function so that potential therapies may be developed to target this process.
Role Of Sphingolipid Signalling In Hepatic Insulin Resistance And Its Application In Prediction Of Risk For Type 2 Diabetes And Prediabetes
Funder
National Health and Medical Research Council
Funding Amount
$563,305.00
Summary
Type 2 diabetes is expected to reach epidemic proportions in the coming decades. Prediabetes is usually unrecognized and constitutes a major public health concern that needs earlier interventions, because the majority of prediabetic subjects proceed to T2D. We have identified an enzyme that plays an important role in insulin signalling. The possibility is that the level or activity of this enzyme is a potential biomarker of the prediabetes state and could be also used as a target
Control Of The Ras/Erk Signaling Pathway By The Brahma Chromatin-remodeling Complex
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
Hormones bind and initiate molecular signals within cells to proliferate or change into specific cell types. This is important for growth and development of different tissues. A pathway which is critical for transmitting the effects of hormones in cells is the Ras pathway. New studies by the applicants indicate that the Brahma complex, a molecule important in controlling the levels of proteins in cells, activates the Ras pathway. This project will define how Brahma controls the Ras pathway.
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.
Characterising The Novel Signalling Mechanism For A New Interferon
Funder
National Health and Medical Research Council
Funding Amount
$525,485.00
Summary
We have discovered a new regulatory protein called interferon epsilon, made in the female reproductive tract and is crucial for protection against bacterial( Chlamydia) and viral (Herpes Simplex Virus) infections. However, we are yet to understand how it interacts with target cells. This grant will study how IFN? binds to cells and the nature of the signals it transmits. This will help us understand its role in disease and its clinical potential
SETD7-dependent Regulation Of Hippo/YAP And Wnt/beta-catenin Pathways In The Intestine
Funder
National Health and Medical Research Council
Funding Amount
$601,950.00
Summary
Colon cancer accounts for approximately 10% of all cancer-related deaths in Australia. One of the most common causes of colon cancer is a mutation in a signalling pathway called the Wnt/beta-catenin pathway. Despite this knowledge, there are currently no drugs that directly target this pathway to treat colon cancer. We have now identified a new way to control this pathway and have developed a potent and specific drug to block activation of this pathway.
The Role Of PLZF In Regulating The Antiviral Activity Of Interferons
Funder
National Health and Medical Research Council
Funding Amount
$652,005.00
Summary
Interferons are the first line of defence against viral infection. We have shown that the transcription factor promyelocytic leukemia zinc finger protein (PLZF) is a novel regulator of the interferon response. Thus we hypothesize that PLZF is a critical component of the host's innate immune system. This study will provide new insights into the understanding of signal transduction mechanisms, as well as improve our ability to modulate sensitivity to interferon to protect against viral diseases.
An AMPK Myristoyl Switch Controls AMP Mediated Metabolic Stress Signaling
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
This project is investigating an enzyme called AMP-activated protein kinase that plays a pivotal role in controlling how our bodies regulate energy metabolism in response to exercise and diet. Improved understanding of how this enzyme is regulated may provide new therapeutic methods for mimicking the beneficial effects of diet and exercise to treat multiple metabolic diseases including obesity, Type 2 diabetes and cardiovascular disease.
Location, Location, Location: Sub-cellular Specific Targeting Of JNK As A Novel Therapy In Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$633,755.00
Summary
The ‘triple negative’ breast cancer subtype is the most aggressive form of breast cancer, and unlike other subtypes, there are no drugs to specifically this subtype. While many potential drug targets have been identified, they cannot be utilised clinically because of other beneficial roles within the body. We are now deploying our innovative experimental platforms to specifically target the tumour promoting functions of a protein known as ‘JNK’, whilst retaining its beneficial functions.