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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.
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.
A Novel Approach To Cytokine Blockade For The Treatment Of Systemic Lupus Erythematosus
Funder
National Health and Medical Research Council
Funding Amount
$137,700.00
Summary
Lupus is a disease of the immune system which can cause inflammation and damage to many organs and even death, often affecting young people in their prime of life. Current treatments are limited and often have undesirable side effects. Certain cells and molecules are thought to be responsible for causing lupus. This project will examine the effect of blocking one of these molecules as a means of treating lupus. It will also use gene and protein analysis of samples from lupus patients to see if r ....Lupus is a disease of the immune system which can cause inflammation and damage to many organs and even death, often affecting young people in their prime of life. Current treatments are limited and often have undesirable side effects. Certain cells and molecules are thought to be responsible for causing lupus. This project will examine the effect of blocking one of these molecules as a means of treating lupus. It will also use gene and protein analysis of samples from lupus patients to see if response to treatments can be predicted.Read moreRead less
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.
Small Molecule Activators Of Glucagon-like Peptide Receptor
Funder
National Health and Medical Research Council
Funding Amount
$658,152.00
Summary
This project seeks new knowledge about (i) a protein on pancreatic cells that can be stimulated to treat problems associated with type 2 diabetes, and (ii) how to create small molecules that can act on this protein and afford a better treatment for diabetes. Advantages of such a new treatment will be low cost, easy administration as an oral tablet rather than injection, need for minimal supervision and monitoring by medical professionals, and therefore more accessibility to global populations.
Deciphering Signalling Pathways Regulating Iron Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$407,402.00
Summary
Iron overload and anaemia are two of the most significant health problems affecting humans. Understanding how the body regulates iron levels is key to our understanding of these disorders and to the future development of new therapies. This research is aimed at understanding how a hormone produced in the liver called hepcidin that maintains iron balance is regulated. This research may lead to novel therapies aimed at correcting the iron balance in conditions of iron overload or anaemia.
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.
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 Structural Understanding Of Class B G Protein-coupled Receptor Function
Funder
National Health and Medical Research Council
Funding Amount
$1,289,570.00
Summary
G protein-coupled receptors (GPCRs) are the largest family of cell surface proteins that enable communication from external signals to the inside of cells of the body. Class B GPCRs are a therapeutically important subclass of these receptors and they play crucial roles in bone and energy homeostasis, cardiovascular control and immune response. This grant will uncover fundamental knowledge on how these receptors work, and will enhance future development of therapeutics.