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Investigation Of The Roles Of TNFa-related Apoptosis-inducing Ligand, TRAIL, In The Immune System.
Funder
National Health and Medical Research Council
Funding Amount
$436,980.00
Summary
TRAIL, is a newly described member of the tumour necrosis factor (TNF)-family of cytokines, which can kill a wide range of tumour cells, and virus infected cells, but not most normal cells. TRAIL has proven to be safe when administered to normal, tumour bearing, and virally-infected mice, and causes no detectable side-effects in these animals. As such it holds huge potential and is being widely investigated for use as a new anti-cancer therapy. Despite these findings, little is known about the t ....TRAIL, is a newly described member of the tumour necrosis factor (TNF)-family of cytokines, which can kill a wide range of tumour cells, and virus infected cells, but not most normal cells. TRAIL has proven to be safe when administered to normal, tumour bearing, and virally-infected mice, and causes no detectable side-effects in these animals. As such it holds huge potential and is being widely investigated for use as a new anti-cancer therapy. Despite these findings, little is known about the true physiological role of TRAIL in vivo. To define the normal roles of TRAIL, CIA has been characterising TRAIL gene knock-out mice. These studies have confirmed that TRAIL contributes to control of tumours in vivo, and in early events during anti-viral responses. However, these studies have also revealed novel roles for TRAIL in T cell biology, and B cell memory. Understanding how TRAIL contributes to these processes, will shed significant light on the potential of TRAIL to be used as a therapeutic agent for humans with lymphoproliferative disease, for illiciting better long-lived antibody responses such as after vaccination, and as an anti-viral reagent in immunocompromised individuals during virus infection.Read moreRead less
The Ability Of Sunscreens To Protect Against The Induction Of Solar Irradiation-induced Melanocytic Naevi In Vivo.
Funder
National Health and Medical Research Council
Funding Amount
$106,854.00
Summary
Melanoma is an increasing problem in Australia. Strong evidence supports the finding that the number of moles on skin is a good indicator of future melanoma risk and a short term marker of adverse reactions to melanoma-inducing sun exposure in humans. While recommendations for sun protection have been proposed for many years, it is currently unknown what component of sunlight induces melanoma or whether sunscreens protect against the formation of melanoma. Using an animal model for human moles o ....Melanoma is an increasing problem in Australia. Strong evidence supports the finding that the number of moles on skin is a good indicator of future melanoma risk and a short term marker of adverse reactions to melanoma-inducing sun exposure in humans. While recommendations for sun protection have been proposed for many years, it is currently unknown what component of sunlight induces melanoma or whether sunscreens protect against the formation of melanoma. Using an animal model for human moles of the skin we aim in contributing to the answers of these two questions .Read moreRead less
Roles Of Virus-integrin Interactions And Rotavirus Modulation Of Host Cell Responses In Viral Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$474,000.00
Summary
Rotaviruses are the main cause of severe gastroenteritis in children, and cause 1 in 27 Australian children under the age of 5 years to spend time in hospital. There is currently no rotavirus vaccine available. We aim to discover how rotavirus interacts with host cells. This information is necessary to formulate a safe and effective vaccine, or a therapeutic agent that can block virus growth in host cells. Previously, we showed that rotavirus attaches to cells and enters them using several membe ....Rotaviruses are the main cause of severe gastroenteritis in children, and cause 1 in 27 Australian children under the age of 5 years to spend time in hospital. There is currently no rotavirus vaccine available. We aim to discover how rotavirus interacts with host cells. This information is necessary to formulate a safe and effective vaccine, or a therapeutic agent that can block virus growth in host cells. Previously, we showed that rotavirus attaches to cells and enters them using several members of the integrin protein family that are present on the surface of the cells. Integrins are critical for cell adhesion, survival and communication. In this project, we will identify how rotavirus usage of integrins modulates cell functions. This will help us understand how rotavirus causes disease, how virus spreads in the body and how the immune response defends us from rotavirus. Rotavirus binds integrins using particular stretches of protein sequence that we have shown are also present in other human viral pathogens that cause hepatitis, AIDS and measles. We will determine if these other viruses also recognize integrins.Read moreRead less
Elucidating The Molecular Regulation Of Gp130 Complex Signalling In Lipid And Glucose Metabolism.
Funder
National Health and Medical Research Council
Funding Amount
$387,489.00
Summary
Overnutrition promotes obesity, which greatly increases the risk of type 2 diabetes and cardiovascular disease. We have provided evidence that activation of gp130 signalling may enhance insulin action and fatty acid oxidation in metabolically active tissues. My research proposal aims to elucidate the molecular regulation of gp130 complex signalling in lipid and glucose metabolism in important metabolic tissues.