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.
Profiling Global Inflammatory Signatures For GPCRs In Human Macrophages
Funder
National Health and Medical Research Council
Funding Amount
$687,770.00
Summary
Macrophages are important white blood cells of the immune system. They trigger inflammatory responses to infection or injury, but prolonged inflammatory responses can lead to chronic diseases. In this project we aim to better understand how macrophages sense the outside environment, how external signals trigger inflammatory processes, how this leads to diseases such as autoimmune and inflammatory diseases, cancer and cardiovascular diseases, and how to control them with drugs.
Protein Kinase Regulatory Switches: Decision-Making in the Nucleus. This project plans to examine new regulatory mechanisms for an important signalling enzyme in the cell nucleus. It aims to define how this enzyme enters the nucleus, to characterise new modifications that affect its actions, and to establish how a conserved nuclear protein may provide an unexpected regulatory platform to send nucleus-initiated signals back to the cell cytoplasm. This reverse signalling is a novel mechanism for i ....Protein Kinase Regulatory Switches: Decision-Making in the Nucleus. This project plans to examine new regulatory mechanisms for an important signalling enzyme in the cell nucleus. It aims to define how this enzyme enters the nucleus, to characterise new modifications that affect its actions, and to establish how a conserved nuclear protein may provide an unexpected regulatory platform to send nucleus-initiated signals back to the cell cytoplasm. This reverse signalling is a novel mechanism for integrating nuclear actions that has the potential to create a signal transduction circuit triggered by environmental or genetic factors. This information is crucial in defining the molecular logic of signalling events that may be ultimately targeted to control cell growth, differentiation and survival.Read moreRead less
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
Transcription factor nuclear residency as a driver of gene expression. Persistently active proteins can stay in the nucleus to drive cell growth and prevent cell death. This project will define how one specific active protein can remain in the nucleus and regulate gene expression through the action of unique ribonucleic acid (RNA) molecules. The results will enable persistent gene activation to be manipulated in cancer.
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.
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.
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.