Does CD123 Provide A Biological Advantage To Leukaemia Stem Cells?
Funder
National Health and Medical Research Council
Funding Amount
$647,637.00
Summary
Leukaemia is a devastating form of blood cancer affecting both young and old. We need to understand the diseased stem cell to eradicate this disease. Current therapy is poorly tolerated and the majority of patients ultimately die at relapse. We intend to investigate how we can make the cells more susceptible to therapy by understanding their biology.
Exploring And Targeting The Anti-Inflammatory Signalling Mechanisms Of Interleukin 37
Funder
National Health and Medical Research Council
Funding Amount
$1,018,306.00
Summary
Cytokines are messenger proteins that function as master regulators of biological processes; thus they play central roles in many diseases. The rare cytokines that block inflammation do so by dampening the immune system’s potentially destructive force, making them attractive targets for drug development. We showed that interleukin 37 is a powerful anti-inflammatory cytokine, and will now evaluate its mechanisms of action and its efficacy against several severe diseases, including cancer.
Cytokine-driven Allergic Inflammation: Characterization Of Two Isoform-specific Modes Of IL-3 Receptor Activation And Investigation Of New Receptor-associated Signalling Partners.
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
In asthma, the symptoms are caused by an allergic reaction in the lung orchestrated by immune cells which produce small proteins called cytokines thus stimulating inflammatory cell production. The cytokine IL-3 is critical for the production of basophils which have an important role in the inflammation. The project will investigate the molecular details of how the IL-3 binds to its receptor and stimulates basophil production and reveal new targets for controlling inflammation in asthma.
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.
Structural And Functional Analysis Of Oncostatin M Receptor Signalling Complexes
Funder
National Health and Medical Research Council
Funding Amount
$519,284.00
Summary
Understanding how a chemical messenger selectively controls bone formation may lead to development of new therapies for osteoporosis and potentially other important diseases.
Understanding SOCS3 Inhibition Of JAK Activity In Myeloproliferative Disorders
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
The myeloproliferative disorders are diseases in which abnormal blood cell development leads to a risk of stroke, thrombosis, hemorrhage and leukemia. Remarkably, three of these disorders are caused by an error in a single enzyme that makes it over active. The enzyme, JAK2, controls how cells respond to hormone-like messengers called cytokines. We are investigating a cellular pathway that inhibits this enzyme in order to understand the progression and potential treatment of the disorders.
Chronic Lymphocytic Leukemia (CLL) is a very common blood cancer. Leukaemic tumour cells actively shut down key immune defences in patients who are very prone to severe infections. Current chemotherapies further immuno-compromise CLL patients and over a quarter will die from an infection despite having responded to cancer treatments. We propose that restoring key immune functions in CLL is key to improve resistance to infection and restore natural anti-cancer immunity.
Biomarkers For The Diagnosis Of Childhood TB: Validation In A High TB Prevalence Setting
Funder
National Health and Medical Research Council
Funding Amount
$948,086.00
Summary
The WHO highlights the urgent need for new diagnostic tests to combat the global TB pandemic. Diagnosis of TB is particularly difficult in children. In our previous NHMRC-funded Melbourne-based study we found promising diagnostic markers in blood which can differentiate patients with and without TB. This project has the potential to revolutionise the diagnosis of TB by providing data that will enable the development of a new generation of diagnostic tests.
The placenta is essential for fetal-maternal exchange and healthy pregnancy however the factors that are required for the placenta to form are poorly understood. We will investigate how the placenta develops in mice and which are the most important factors that are required for a health placenta to form.