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.
Defining The Role Of A Palmitoylated Variant Of Sphingosine Kinase 1 In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$603,452.00
Summary
Sphingosine kinase is a protein that when dysregulated is involved in cancer development and progression. We have recently made a substantial breakthrough in this area by identifing a naturally occuring variant of sphingosine kinase that is constantly activated and has an enhanced ability to induce cancer. In this study we will examine and target this form of sphingosine kinase as a potential therapeutic intervention in cancer.
Dissecting Rapamycin Sensitive And Insensitive Effects Of MTOR
Funder
National Health and Medical Research Council
Funding Amount
$1,183,241.00
Summary
All cells possess machinery that can sense nutrient availability and trigger cell growth and nutrient storage pathways. However, nutrient oversupply is detrimental to health. Recently, it was shown that drugs that inhibit the nutrient sensors have life extending effects. Our laboratory has discovered a novel mechanism by which these drugs might be mediating these beneficial effects that could change the way we think about the beneficial effects of these drugs and their mode of action
Sphingosine Kinase As A Target For Anti-cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$590,785.00
Summary
Sphingosine kinase is a protein involved in the development and progression of numerous types of solid tumors and leukaemias. We have recently made a major break-through by identifing how the cancer-inducing activity of sphingosine kinase is controlled. In this study we will target these control mechanisms to develop potential new anti-cancer therapies.
New Insights Into Mechanisms That Coordinate Kinase Signalling And Molecular Motors In Mitosis: A Novel Role For The Protein Scaffold WD-repeat Protein 62 (WDR62).
Funder
National Health and Medical Research Council
Funding Amount
$529,122.00
Summary
Proteins perform all functions within a cell. Commonly, different proteins are assembled into large complexes to carry out processes, such as cell division, with significant implications for human health. Scaffold proteins facilitate the proper assembly of large complexes but are a poorly understood protein class. We will perform molecular analysis of a newly discovered scaffold, WDR62, to define how it drives cell division and reveal how this can be exploited to develop new anti-cancer drugs.
Structural And Functional Analysis Of Oncostatin M Receptor Signalling Complexes
Funder
National Health and Medical Research Council
Funding Amount
$519,284.00
Summary
Understanding how a chemical messenger selectively controls bone formation may lead to development of new therapies for osteoporosis and potentially other important diseases.
The Characterization Of A Novel Pseudokinase Regulator Of Platelet Formation
Funder
National Health and Medical Research Council
Funding Amount
$372,965.00
Summary
Mammalian cells contain a complex switchboard, which directs the cell to grow, die, multiply or move in response to external cues. When communication breaks down within the cell, diseases arise. Our studies are directed towards identifying the molecules that comprise the switchboard which directs blood cell formation. A detailed understanding of the regulators of blood cell formation will equip us with a sound starting point for designing drugs to ameliorate blood diseases.
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.
Characterization Of SgK269, A Master Regulator Of Growth Factor Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$623,751.00
Summary
Perturbed signaling within a cell can cause multiple diseases, including cancer. SgK269 is a scaffold protein involved in signaling and implicated in breast, colon and pancreatic cancer. By determining the signaling mechanism and function of the SgK269 scaffold, this work will provide novel and important insights into a key regulator of cell signaling, and reveal potential strategies for therapeutic targeting of the SgK269 scaffold that could be utilized in cancer treatment.