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.
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
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.
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.
Characterisation Of Two New Kinases In The Hippo Tumour Suppressor Pathway
Funder
National Health and Medical Research Council
Funding Amount
$550,602.00
Summary
The Hippo pathway is a key regulator of tissue growth. It was first discovered in vinegar flies and plays a similar role in mammals. We aim to define the mechanism by which the Gish and Fray kinases control tissue growth by regulating the Hippo pathway. These studies will be performed in flies and mammalian cell culture. Our studies will shed light on how tissue growth is controlled, and have the potential to inform the way that we treat human cancers and tissue growth disorders.
Why Is The Hijacking Of A Human Erythrocyte Signalling Pathway Essential For Malaria Infection?
Funder
National Health and Medical Research Council
Funding Amount
$510,890.00
Summary
Malaria drug resistance is spreading and the world needs cost-effective new drugs. We found 2 human enzymes, known targets of cancer chemotherapy, to be key for parasite survival in red blood cells. We aim to understand why these human proteins are crucial for the parasite and to identify new human proteins hijacked by malaria. This will open exciting options for antimalarial drug discovery: to harness funds invested in cancer drugs by targeting proteins with dual roles in cancer and malaria.
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.
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
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.
New Mediators Of GPCR-growth Factor Receptor Transactivation
Funder
National Health and Medical Research Council
Funding Amount
$607,842.00
Summary
Hormones bind to receptors on the surface of cells. Receptors can modify each other’s function and this “cross-talk” is important for the receptors for a peptide hormone (termed angiotensin) and a growth factor receptor (EGFR), which are major regulators of the cardiovascular system. We have identified a number of mediators of the angiotensin-EGFR crosstalk and this current grant aims to use molecular and cellular and in vivo approaches to examine the molecular basis of their actions.