Aquaporin channels in cell migration. The project aims to determine the role of Aquaporin1 (AQP1) in enhancing rapid cell motility. Cell migration is important for development, repair, and protection in multicellular organisms. AQP1 is increased in some rapidly migrating cell types. Loss of AQP1 impairs migration, which is restored by reintroduction of AQP1 but not AQP4. Expected outcomes include defining the features of AQP1 that confer enhanced cell migration. The project will test the hypothe ....Aquaporin channels in cell migration. The project aims to determine the role of Aquaporin1 (AQP1) in enhancing rapid cell motility. Cell migration is important for development, repair, and protection in multicellular organisms. AQP1 is increased in some rapidly migrating cell types. Loss of AQP1 impairs migration, which is restored by reintroduction of AQP1 but not AQP4. Expected outcomes include defining the features of AQP1 that confer enhanced cell migration. The project will test the hypothesis that dual water and ion channel functions of AQP1 are needed for movement, using migration assays in cells with wild type and mutant AQP1, and selective pharmacological agents developed by the project team to dissect the essential channel properties that enable rapid migration in cancer and stem cells. The project seeks to build knowledge of AQP roles in development, regeneration and surveillance, potentially improving health care by revealing pathways in migration disorders such as metastasis.Read moreRead less
Fundamental roles of aquaporin-1 channels in cell migration and morphology. This project aims to investigate cell migration mechanisms and the roles of aquaporin channels in controlling cell motility and morphology. The ability of cells to move and maintain proper shape is important for development, repair and survival in multicellular organisms. This project will test the role of mammalian aquaporin-1 channels in enabling rapid migration in normal and cancer cells, in repairing barrier layers i ....Fundamental roles of aquaporin-1 channels in cell migration and morphology. This project aims to investigate cell migration mechanisms and the roles of aquaporin channels in controlling cell motility and morphology. The ability of cells to move and maintain proper shape is important for development, repair and survival in multicellular organisms. This project will test the role of mammalian aquaporin-1 channels in enabling rapid migration in normal and cancer cells, in repairing barrier layers in kidney and brain, and in allowing red blood cells to maintain the classic disk-shape needed for optimal transport. Outcomes will define features of aquaporin-1 that provide these functions, using molecular, optical and pharmacological tools. Results will define aquaporin channel properties that enable optimal cellular function.Read moreRead less
Molecular mechanisms regulating Ca2+ channels formed by Orai and STIM proteins. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, antigens, growth factors and other physiological stimuli. The aims of this project are to elucidate cellular mechanisms that regulate interaction between the molecular components of store-operated calcium channel, Orai and STIM. Using techniques of electrophysiol ....Molecular mechanisms regulating Ca2+ channels formed by Orai and STIM proteins. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, antigens, growth factors and other physiological stimuli. The aims of this project are to elucidate cellular mechanisms that regulate interaction between the molecular components of store-operated calcium channel, Orai and STIM. Using techniques of electrophysiology and molecular biology we expect to answer a fundamental question how STIM and Orai proteins interact to form functional store-operated calcium channels, and how the expression of STIM and Orai is regulated.Read moreRead less
Why is the peribacteroid membrane transcription factor SAT1 required for legume nitrogen fixation and what is its role in other symbiotic systems? This project will investigate the functional activity of the plant membrane bound basic helix-loop-helix (bHLH) transcription factor SAT1 in both nitrogen fixing (Rhizobia) and phosphorus acquiring (Arbuscular Mycorrhizal) symbioses found in plants. The project will identify its regulation and downstream activities across both symbiosis using selected ....Why is the peribacteroid membrane transcription factor SAT1 required for legume nitrogen fixation and what is its role in other symbiotic systems? This project will investigate the functional activity of the plant membrane bound basic helix-loop-helix (bHLH) transcription factor SAT1 in both nitrogen fixing (Rhizobia) and phosphorus acquiring (Arbuscular Mycorrhizal) symbioses found in plants. The project will identify its regulation and downstream activities across both symbiosis using selected legumes and or cereals.Read moreRead less
Exploring the immunomodulatory potential of Natural Killer T cells. Natural Killer T cells (NKT cells) are an innate-like population of T cells that recognise a range of lipid based antigens when bound to the antigen-presenting molecule, CD1d. Once activated, NKT cells rapidly secrete a variety of cytokines. This project, in partnership with Vaxine Pty Ltd, aims to gain a basic understanding of NKT recognition of lipids and NKT cell activation by lipids. The project aims to use a combination of ....Exploring the immunomodulatory potential of Natural Killer T cells. Natural Killer T cells (NKT cells) are an innate-like population of T cells that recognise a range of lipid based antigens when bound to the antigen-presenting molecule, CD1d. Once activated, NKT cells rapidly secrete a variety of cytokines. This project, in partnership with Vaxine Pty Ltd, aims to gain a basic understanding of NKT recognition of lipids and NKT cell activation by lipids. The project aims to use a combination of cellular immunology and structural biology to gain insight into NKT cell agonism.Read moreRead less
The Clinical Significance Of Sex Hormone Crosstalk In Estrogen Receptor Positive Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$1,009,006.00
Summary
Breast cancer is mainly a disease in which the sex hormone estrogen stimulates uncontrolled growth. We have recently discovered that other sex hormones, including progesterone and androgen, can redirect the actions of estrogen in breast cancers to halt growth or make a tumour disappear. This study will examine the complex interaction between all three sex hormones to develop new, more effective strategies for treating breast cancer.
How The Lateral Habenula Integrates Behavioral And Autonomic Functions: The VTA Dopamine Connection
Funder
National Health and Medical Research Council
Funding Amount
$819,904.00
Summary
When adverse events occur, the lateral habenula, an old brain nucleus, helps calculate the wisest corrective action by contributing to the “brake” that controls the brain’s dopamine reward system. Our research will show how the lateral habenula links corrective changes in behavior with coordinated changes in temperature. Understanding this link will greatly contribute to understanding the brain mechanisms that regulate our physiology during stressful situations and as part of mental illness.
Chronic inflammation underlies common and debilitating diseases and causes pain by unknown mechanisms. There is an urgent need to gain a deeper understanding of the mechanisms of chronic pain, which will allow the development of improved therapies with fewer side-effects. Our research program investigates the mechanisms of pain that are associated with inflammatory bowel disease and irritable bowel syndrome, with the goal of developing more effective and selective therapies.
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.