The Novel CXCR4/CCR7 Heterodimeric Chemokine Receptor Is A Key Determinant Of Breast Cancer Metastasis.
Funder
National Health and Medical Research Council
Funding Amount
$461,252.00
Summary
Novel cellular receptor has been identified that works as a switch to turn on cellular functions that are responsible for the metastatic dissemination of cancer cell to distant organs. The make-up and regulatory mechanisms of this novel receptor will be studied together with its potential utility as the marker of metastatic breast cancer.
Characterisation Of The Adiponectin Receptors - AdipoR1 And AdipoR2
Funder
National Health and Medical Research Council
Funding Amount
$445,158.00
Summary
The increasing incidence of cardiometabolic disease highlights an unmet need for novel therapeutic approaches. Greater understanding of the detail governing cardiometabolic function is required to provide a foundation to construct effective strategies. We will characterise 2 novel receptors that are important in the regulation and maintenance of cardiometabolic systems, seeking to identify strategies to enhance receptor, improve cardiometabolic function and reduce disease burden.
A New Paradigm For Class I Cytokine Receptor Activation
Funder
National Health and Medical Research Council
Funding Amount
$954,946.00
Summary
Class I cytokine receptors include around 30 receptors with diverse functions such as controlling metabolism and inflammation. Cytokine receptors are molecular switches on cells that receive signals from other cells and transmit this signal into the cell’s nucleus to control the regulation of genes. This project will determine the molecular mechanisms involved in class I cytokine receptors and use this knowledge to develop novel ways to modulate these receptors for clinical applications.
Macrophage Polarisation And Control Of Pulmonary Inflammation.
Funder
National Health and Medical Research Council
Funding Amount
$895,494.00
Summary
As key immune cells, macrophages are polarised to phenotypes that turn inflammation on or off. In cystic fibrosis, defective macrophage polarisation enhances inflammation and prevents lung repair. We are defining the molecules and cellular pathways that control this process and identifying targets for existing drugs that can be used to reprogram macrophages and restore lung repair to improve patient outcomes.
Novel Approaches To Control Mast Cell Function In Allergic Inflammation.
Funder
National Health and Medical Research Council
Funding Amount
$723,447.00
Summary
Allergic disorders are a major health problem. Driven by mast cells, the underlying inflammation is exacerbated by the ‘?c family’ of cytokines acting on the surface of these cells. We aim to characterise the ‘mast cell-?c axis’ with the view to developing new therapies based on our ?c receptors blocking antibodies. This path of discovery-mechanism-translation seeks to recapitulate our previous success of taking a related antibody to Phase II clinical trials to treat patients with leukaemia.
Mechanisms Of Ligand-Selective Signalling By Chemokine Receptors
Funder
National Health and Medical Research Council
Funding Amount
$749,428.00
Summary
Receptors are molecules located on the surfaces of cells. They control the response of one cell to chemical signals emitted by different cells. In this project we aim to characterise and understand the molecular details of how a receptor can respond differently to distinct chemical signals. The results of this study will help to guide future development of medicines to control white blood cell migration into tissues during inflammatory diseases such as heart disease, diabetes and arthritis.
The regulation to early T cell signalling is a critical step in immune responses. Superimposed onto the biochemical pathways is a spatial organization that defines the immunological synapse. My research aims to map the principles of the spatial organization on the molecular scale to identify how lipids could unbalance the dynamic signalling equilibrium, for example in obese patients. To achieve this goal, my research group has developed single molecule microscopy approaches.
I study hormone action at the molecular level, particularly that of growth hormone action. I focus on the mechanism of activation of its receptor, notably as a target for cancer therapy, since growth hormone is necessary for the progression of many types of cancer. The ability of growth hormone to activate neural stem cells for a prolonged period in response to voluntary exercise is also a key interest. So too is the 40% extension of lifespan in mice after genetically deleting the growth hormone ....I study hormone action at the molecular level, particularly that of growth hormone action. I focus on the mechanism of activation of its receptor, notably as a target for cancer therapy, since growth hormone is necessary for the progression of many types of cancer. The ability of growth hormone to activate neural stem cells for a prolonged period in response to voluntary exercise is also a key interest. So too is the 40% extension of lifespan in mice after genetically deleting the growth hormone receptor.Read moreRead less
Mitogenic And Metabolic Signalling Via The Insulin Recptor Isoform-A
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
A novel mechanism of stimulating cancer cell survival and growth has been identified which involves insulin and insulin-like growth factor-II acting via the insulin receptor isoform A. This proposal will identify the mechanisms by which these ligands stimulate growth rather than metabolism via the insulin receptor-A. This information will be used in future design of novel molecules to inhibit cancer growth without interfering with insulin's normal metabolic functions.
Mechanism Of Activation Of JAK2 By A Class 1 Cytokine Receptor
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
Cytokine receptors regulate key processes such as red/white blood cell formation, stature, adiposity and lactation. They use JAK kinases to signal to regulated genes. Here we will use sophisticated technologies able to observe single molecules and crystallography to uncover the mechanism used by these receptors to signal into the cell using a well characterised, simple cytokine receptor, the growth hormone receptor.