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.
A Novel Class Of Negative Regulators Of Interleukin-6 Signalling
Funder
National Health and Medical Research Council
Funding Amount
$626,950.00
Summary
Cytokines are protein messengers that activate the immune system to fight infections. When they are too active they cause inflammation and autoimmune diseases so their activity needs to be tightly controlled. We have discovered a new family of regulators (the MARCH proteins) that inhibit cytokine activity by routing cytokine receptors for destruction. We aim to understand how this process works in detail and the role of MARCH proteins in vivo in ameliorating autoimmune diseases.
Characterization Of A Novel IFNbeta Signaling Axis Mediated Via IFNAR1
Funder
National Health and Medical Research Council
Funding Amount
$353,754.00
Summary
Type I interferons (IFNs) play an important role in regulating immune responses to pathogens and tumors and are used therapeutically. This project will investigate a novel IFN signaling axis that we have recently characterized that is mediated via the low affinity IFN receptor, IFNAR1. This signaling axis occurs independently of the high affinity IFN receptor IFNAR2 and contributes to lethality in a model of septic shock.
Analysis Of The Functions Of A Novel Class Of Ubiquitin E3 Ligases In TNF Signalling In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$568,861.00
Summary
The aim of this project to discover the role of a novel ubiquitin ligase complex that regulates TNF superfamily signalling. It will increase understanding of the TNF pathway and improve our ability to manipulate it pharmacologically, or otherwise, in the large number of debilitating human diseases including Rheumatoid Arthritis and Crohn's disease that result from aberrant TNF signalling. Because of the role of TNF in tumorigenesis it may also contribute to novel anti-cancer treatments.
Interferon Regulatory Factor 6: A Novel Epithelial-specific Regulator Of Mucosal Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$517,989.00
Summary
Epithelial cells lining the respiratory and gastrointestinal tracts play pivotal roles in protecting us from infection. Inflammatory factors released by epithelial cells are important for fighting infection; however, they also contribute to chronic inflammatory diseases. We aim to understand how a protein called IRF6 regulates the inflammatory response of epithelial cells. The knowledge gained will identify new therapeutic approaches for inflammatory diseases.
New Mediators Of GPCR-growth Factor Receptor Transactivation
Funder
National Health and Medical Research Council
Funding Amount
$607,842.00
Summary
Hormones bind to receptors on the surface of cells. Receptors can modify each other’s function and this “cross-talk” is important for the receptors for a peptide hormone (termed angiotensin) and a growth factor receptor (EGFR), which are major regulators of the cardiovascular system. We have identified a number of mediators of the angiotensin-EGFR crosstalk and this current grant aims to use molecular and cellular and in vivo approaches to examine the molecular basis of their actions.
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.
Regulation Of The Signalling Efficiency Of The T Cell Antigen Receptor
Funder
National Health and Medical Research Council
Funding Amount
$456,557.00
Summary
An immune response starts with activation of the T cell antigen receptor (TCR). How T cell receptor signalling begins, however, is not well understood. We have developed a novel imaging approach that allows us to directly observe what happens after an antigen binds to the receptor. The research will provide mechanistic insights into how T cells sense and discriminate antigens. This knowledge will aid the development of cancer immunotherapies and vaccines.
Spatial And Temporal Dimensions Of Mu-opioid Receptor Signalling: Implications For The Development Of Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$799,316.00
Summary
The use of morphine as an analgesic is still limited by undesirable side effects such as tolerance. Despite decades of research, the mechanisms behind the development of tolerance are poorly understood. The ? opioid receptor is a protein expressed at the surface of the cells that is the target of morphine. This project will investigate the signalling events triggered by opioids with unprecedented resolution and will aim to elucidate why morphine elicits more tolerance than other opioid drugs.
Overcoming Therapeutic Resistance In Pancreatic Cancer
Funder
National Health and Medical Research Council
Funding Amount
$924,901.00
Summary
Pancreatic cancers arise when abnormal cells grow out from otherwise normal tissue. The resulting tumours contain a number of different types of cells, some of which help the tumour to grow, and some of which fight the tumour. We are interested in understanding how soluble molecules called cytokines influence the cells that promote tumour growth and metastasis. In particular, we will test whether cytokine inhibitors can overcome tumour resistance to chemotherapy.