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
T cells play a central role in the immune response. The primary event in T cell activation is the triggering of a specific T cell receptor (TCR). Our studies will define new mechanisms for the regulation of TCR-mediated T cell responses. Our studies may yield novel insight into processes that contribute to the development of type 1 diabetes & inflammatory bowel disease.
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.
Targetting The CIB1-sphingosine Kinase Interaction In Oncogenesis
Funder
National Health and Medical Research Council
Funding Amount
$805,034.00
Summary
Sphingosine kinase is a protein involved in cancer development and progression. We have identified that the cancer-inducing activity of sphingosine kinase is controlled by another protein called CIB1 which itself appears involved in causing cancer by deregulating sphingosine kinase. In this study we will examine and target the interaction between sphingosine kinase and CIB1 as a potential therapeutic intervention in cancer.
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.
Ciliopathies are an emerging group of syndromes in society that have devastating health effects. Ciliopathy patients exhibit a specturm of disorders including polycystic kidneys, extra digits, retinal degeneration and neural tube defects. INPP5E is a gene that is mutated in patients with a ciliopathy syndrome. These studies will determine the role of INPP5E in ciliopathy disease and may identify INPP5E as a novel treatment target.
Only recently has it emerged that our cells have a built-in backup mechanism that instructs cells to die in extreme cases, such as when viruses have hijacked a cell. A misfiring backup mechanism is thought to underlie a number of human diseases, including inflammatory disease. Our investigation will establish a starting point for the development of novel anti-inflammatory drugs.
Tao Kinase, A New Member Of The Hippo Tumour Suppressor Pathway
Funder
National Health and Medical Research Council
Funding Amount
$605,190.00
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 Tao kinase controls 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.
Dissecting The Role Of Insulin-regulated Phosphorylation Of Rab Guanine Nucleotide Exchange Factors In GLUT4 Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$628,459.00
Summary
Diabetes and obesity are epidemic in the developed world. Impaired insulin action is a major cause. A key contributor is reduced glucose uptake into muscle and fat driving the pancreas to overproduce insulin. We have recently discovered three new molecules that we believe hold the secret to how insulin regulates the removal of the glucose from the blood stream after a meal. This proposal focuses on these three molecules and their regulation.
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.