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
Studies Of Cullin 5 Deficiency For Novel Insights Into SOCS Redundancy And Specificity
Funder
National Health and Medical Research Council
Funding Amount
$658,571.00
Summary
Cytokines are hormones that regulate blood cell production and function. The research proposed in this application focuses on the biological roles and biochemical mechanisms of action of an important family of proteins that control the actions of cytokines, thereby allowing their beneficial effects in coordinating oxygen transport, blood clotting and responses to infection, while preventing the harmful effects of excess responses, such as myeloproliferative diseases or autoimmunity.
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.
Elucidating Crosstalk Between RhoGTPases And Polarity Proteins: The Interface Between Morphology, Immune Function And Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$627,549.00
Summary
Major breakthroughs in cancer and autoimmunity require understanding the molecular basis of by which cell behaviour is controlled. We now know the key molecular players, but still need to determine how they interact within the cell to develop the best treatments and diagnostics. Recent breakthroughs now enable us to “watch” molecular interactions within the cell. We will use these approaches to determine how a key molecular switch is regulated in immune cells and cancer cells.
The Role Of Cell Death Pathways In Inflammation And Pathogen Infection
Funder
National Health and Medical Research Council
Funding Amount
$415,218.00
Summary
Cell death and inflammation are essential for protection against pathogen infection but can also cause human diseases. Inflammation caused by the IL-1? protein has been implicated in diseases such as type II diabetes, arthritis and cancer. This project aims to elucidate how IL-1? protein activity is regulated at the molecular level. It also seeks to understand how the pathogen responsible for Legionnaires’ disease manipulates cell death to allow for successful invasion of the human host.
Understanding The Role Of The Atypical Cadherin Fat4 In Lymphatic Vascular Development
Funder
National Health and Medical Research Council
Funding Amount
$1,006,248.00
Summary
This application will define the role of a large cell adhesion molecule, FAT4, in lymphatic vascular development. By understanding how FAT4 functions in lymphatic vessels, we will gain insight to the mechanisms by which mutations in the gene that encodes this protein cause a human lymphoedema syndrome.
The Emergence Of Dead Enzymes As Signal Transducers And Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$463,652.00
Summary
The cells within our bodies are constantly being replenished by new cells. Removal of old cells is typically fast and without fanfare. However, in some cases, cell death can be used to evoke an inflammatory response. My work examines the molecular details of how this happens and how we might advance our knowledge to develop novel drugs to prevent inflammatory diseases, such as Crohn's disease and psoriasis.
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.