T cells play a central role in the immune response. The primary event in T cell activation is the triggering of a specific T cell receptor (TCR). Our studies will define new mechanisms for the regulation of TCR-mediated T cell responses. Our studies may yield novel insight into processes that contribute to the development of type 1 diabetes & inflammatory bowel disease.
Interleukin-1β Biology: Mechanisms Of Regulation, Activation And Secretion
Funder
National Health and Medical Research Council
Funding Amount
$641,979.00
Summary
The protein called intelreukin-1 (IL-1) is required to fight off invading pathogens but more recently has been implicated as contributing to diverse diseases characterised by excessive inflammation, such as arthritis, gout, atherosclerosis and even cancer. This project aims to understand how IL-1 is made within cells and then activated to cause inflammation, which will enable these processes to be therapeutically targeted.
The Role Of PLZF In Regulating The Antiviral Activity Of Interferons
Funder
National Health and Medical Research Council
Funding Amount
$652,005.00
Summary
Interferons are the first line of defence against viral infection. We have shown that the transcription factor promyelocytic leukemia zinc finger protein (PLZF) is a novel regulator of the interferon response. Thus we hypothesize that PLZF is a critical component of the host's innate immune system. This study will provide new insights into the understanding of signal transduction mechanisms, as well as improve our ability to modulate sensitivity to interferon to protect against viral diseases.
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.
How Lipids Affect Signalling Efficiencies In T Cells
Funder
National Health and Medical Research Council
Funding Amount
$472,882.00
Summary
A high fat diet can compromise the function our immune system. This project examines how lipids affect T cells. We propose that T cells from mice on a high fat diet can no longer respond to an immune challenge because the signalling processes that lead to activation are deregulated. We have established a new microscopy technique that allows us to measure the efficiency of signalling processes. We will use this method to identify which lipids contribute the most to T cell deregulation.
Spatial Organization Of Lck As A Regulatory Mechanism Of TCR Signalling
Funder
National Health and Medical Research Council
Funding Amount
$601,263.00
Summary
To function in an immune response, T cell become activated when the interactions between the T cell receptor and the kinase Lck on the cell surface results in intracellular signals. Here, we will investigate how the kinase is organized on the cell surface during receptor activation and what intrinsic and extrinsic parameters regulate its organization. The research is based on novel single molecule imaging tools and will provide new insights into the regulation of T cell activation.
Regulation Of Interleukin-1? Activation In Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$624,429.00
Summary
IL-1? protein is required to combat infection but also contributes to inflammatory diseases, such as Rheumatoid arthritis and diabetes. Understanding how IL-1? is produced is therefore critical to the development of better therapeutics for these conditions. We have identified a new pathway involving the protein RIP3 that can cause IL-1? activation. This project will examine how this pathway is molecularly regulated and determine its importance in inflammatory disease models.
Nuclear alarmins escalate tissue immune responses. Humans and other animals are constantly exposed to potential threats, including microbes on and near the body. Animals can live with such dangers because these everyday encounters are made harmless by the immune system. It is unclear how cells distinguish low-danger threats from high-danger threats. This proposal seeks to reveal how immune cells identify increasing levels of threat and appropriately escalate their responses. Expected outcomes in ....Nuclear alarmins escalate tissue immune responses. Humans and other animals are constantly exposed to potential threats, including microbes on and near the body. Animals can live with such dangers because these everyday encounters are made harmless by the immune system. It is unclear how cells distinguish low-danger threats from high-danger threats. This proposal seeks to reveal how immune cells identify increasing levels of threat and appropriately escalate their responses. Expected outcomes include new insights into how immune cells and tissues respond according to the posing threat. Project benefits include understanding how to manipulate danger responses for future basic research and commercial applications, and fundamental understanding of how animals flourish in a dangerous world.Read moreRead less
A novel mechanism of host defence via macrophage extracellular traps. Animal health relies upon innate immune cells to rapidly detect invading microbes and induce inflammatory and antimicrobial responses to clear infection. Mechanisms of inflammation and immune defence are only partly understood. This project aims to elucidate a novel innate immune pathway (the inflammasome) that drives inflammatory cell death and antimicrobial defence. Using innovative multidisciplinary methods, this project wi ....A novel mechanism of host defence via macrophage extracellular traps. Animal health relies upon innate immune cells to rapidly detect invading microbes and induce inflammatory and antimicrobial responses to clear infection. Mechanisms of inflammation and immune defence are only partly understood. This project aims to elucidate a novel innate immune pathway (the inflammasome) that drives inflammatory cell death and antimicrobial defence. Using innovative multidisciplinary methods, this project will yield exciting new knowledge of mechanisms of inflammation and anti-microbial responses, and new paradigms for inflammasome action. Expected outcomes and benefits include high-impact publications, international collaboration, world-class training for young scientists, and new knowledge for future commercialisation.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220100823
Funder
Australian Research Council
Funding Amount
$442,482.00
Summary
Elucidating ATPase function during NLRP3 inflammasome assembly. Humans and animals are constantly exposed to microbes, which inhabit their external environment as well as body surfaces such as the skin and gut. We are, however, able to co-exist with these microbes, because our immune system protects us from these everyday encounters. This proposal will reveal how an important immune protein called NLRP3 senses microbes and other physiological processes. When NLRP3 senses such factors and is acti ....Elucidating ATPase function during NLRP3 inflammasome assembly. Humans and animals are constantly exposed to microbes, which inhabit their external environment as well as body surfaces such as the skin and gut. We are, however, able to co-exist with these microbes, because our immune system protects us from these everyday encounters. This proposal will reveal how an important immune protein called NLRP3 senses microbes and other physiological processes. When NLRP3 senses such factors and is activated, it induces the release of messenger substances to alert other immune cells. This research will deliver fundamental knowledge of how animals normally co-exist with microbes.Read moreRead less