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.
Assembly And Function Of Two Interacting Oncogenic Scaffolds
Funder
National Health and Medical Research Council
Funding Amount
$705,585.00
Summary
Aberrant signaling by the protein kinase superfamily is a known driving force for many cancers and inflammatory diseases. Recently, a subset of kinase-like proteins, termed pseudokinases, have emerged as crucial regulators of kinase signalling pathways. This proposal focuses on elucidating the scaffolding function and assembly of two pseudokinases, termed SgK223 and SgK269, which display oncogenic properties and aims to understand how their signalling abilities are subverted in a disease state.
Regulation Of Ca2+/calmodulin Dependent Protein Kinase Kinase-2 By Phosphorylation
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
This project will study the regulation of an enzyme called CaMKK2, which plays a pivotal role in controlling a number of important biological functions including brain development, regulation of appetite, energy metabolism and blood pressure. Understanding how this enzyme is regulated may open new avenues for treating Type 2 diabetes, obesity, and cardiovascular disease.
Triple negative breast cancer (TNBC) is an aggressive disease subtype that lacks targeted therapies. We have identified a protein associated with TNBC termed SgK269 that regulates the transmission of signals instructing the cell to grow and migrate. SgK269 associates with a closely-related protein termed SgK223 to form a signalling complex. The aim of this project is to characterise the role of this signalling complex in TNBC and determine whether it represents a potential therapeutic target.
Cytokine-driven Allergic Inflammation: Characterization Of Two Isoform-specific Modes Of IL-3 Receptor Activation And Investigation Of New Receptor-associated Signalling Partners.
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
In asthma, the symptoms are caused by an allergic reaction in the lung orchestrated by immune cells which produce small proteins called cytokines thus stimulating inflammatory cell production. The cytokine IL-3 is critical for the production of basophils which have an important role in the inflammation. The project will investigate the molecular details of how the IL-3 binds to its receptor and stimulates basophil production and reveal new targets for controlling inflammation in asthma.
Identification Of New Mechanisms In Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$478,781.00
Summary
Type II diabetes is a major cause of disease in Australia. Resistance of the liver to the effects of insulin plays a key role in the uncontrolled blood glucose levels in this disease. In this proposal, we will combine state-of-the-art protein chemistry techniques with advanced statistical analysis to identify the pathways driving liver insulin resistance. We will also predict clinically-approved drugs that may reverse these changes, to guide drug development for future therapeutic gain.
The dramatic increase in obesity and age-related metabolic disorders demonstrates the importance of gaining a better understanding of how cells and organisms regulate their energy stores. This project will identify novel molecular mechanisms that control the enzyme CaMKK2, which is a key regulator of whole-body energy metabolism. This will provide new opportunities to inform more effective strategies to tackle metabolic diseases, and improve health in an increasingly ageing population.
Mammalian cells have developed a complex signalling network responsible for monitoring and responding to changes in the levels of growth factors and the availability of nutrients, energy and oxygen in their environment. Deregulation of this network often results in uncontrolled cell growth and diseases including cardiac hypertrophy and cancer. This proposal aims to understand how this network controls cell growth and identify potential targets for diseases driven by uncontrolled growth.
Tyrosine Kinase Signalling Networks In Pancreatic Cancer: Relevance To Therapeutic Response And Biomarker Development
Funder
National Health and Medical Research Council
Funding Amount
$789,934.00
Summary
Pancreatic cancer is a devastating disease characterized by a lack of effective treatments and biomarkers that identify the best way to treat individual patients. By identifying a novel basis for pancreatic cancer subclassification using cutting edge techniques, we aim to identify therapeutic strategies that can be directed to pancreatic cancer patients in a subgroup-selective manner to ultimately lead to reductions in the morbidity and mortality associated with this devastating disease.
Obesity is caused by an energy imbalance, where energy intake from eating food exceeds energy expended by physical exertion and metabolism. This proposal will provide a fundamental advance in our understanding of how the brain communicates with fat to control energy expenditure and body weight.