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.
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.
Using viral inhibitors to understand the regualtion of apoptosis. Apoptosis is a form of cell death that is critical for the development and well-being of multicellular organisms. The activity of Bak or Bax, two members of the Bcl-2 family, are essential for apoptosis to proceed, but how the activity of these two proteins is regulated is unclear. Many viruses encode inhibitors of apoptosis and the project will make use of two novel viral inhibitors that specifically target Bak. The project aims ....Using viral inhibitors to understand the regualtion of apoptosis. Apoptosis is a form of cell death that is critical for the development and well-being of multicellular organisms. The activity of Bak or Bax, two members of the Bcl-2 family, are essential for apoptosis to proceed, but how the activity of these two proteins is regulated is unclear. Many viruses encode inhibitors of apoptosis and the project will make use of two novel viral inhibitors that specifically target Bak. The project aims to determine how the Bak inhibitors function and to provide valuable insights into the normal mechanisms regulating Bak activity.Read moreRead less
Molecular determinants of inflammatory caspase activity upon inflammasomes. Most processes fundamental to life rely on the timely, and regulated, execution of cellular functions. The innate immune system, in which both timing and regulation is paramount, rapidly detects invading microbes and induces a measured and timely antimicrobial response to clear infection. This project aims to address a key knowledge gap by characterising a mechanism for timely and controlled immune system activation and ....Molecular determinants of inflammatory caspase activity upon inflammasomes. Most processes fundamental to life rely on the timely, and regulated, execution of cellular functions. The innate immune system, in which both timing and regulation is paramount, rapidly detects invading microbes and induces a measured and timely antimicrobial response to clear infection. This project aims to address a key knowledge gap by characterising a mechanism for timely and controlled immune system activation and immune cell death via the non-canonical inflammasome. We do not currently understand how some immune pathways are turned on or off. This project will yield fundamental insight into mechanisms of mammalian inflammasome, inflammation and anti-microbial responses.Read moreRead less
How cell shape regulators control cell competition in tissue development. This project aims to determine how cell shape (polarity) regulators affect cell survival in an epithelial tissue. When mutation or wounding perturb cell shape regulators in a tissue cell, signalling pathways are altered that kill the aberrant cells. A surveillance mechanism termed "cell competition" is important to remove the damaged cells. This project will investigate a potential regulator of cell competition, the tyrosi ....How cell shape regulators control cell competition in tissue development. This project aims to determine how cell shape (polarity) regulators affect cell survival in an epithelial tissue. When mutation or wounding perturb cell shape regulators in a tissue cell, signalling pathways are altered that kill the aberrant cells. A surveillance mechanism termed "cell competition" is important to remove the damaged cells. This project will investigate a potential regulator of cell competition, the tyrosine phosphatase PTP61F, in response to perturbation of cell shape regulators, using the vinegar fly, Drosophila, and mammalian systems. This study is expected to reveal biomarkers that can be used to improve organismal fitness to increase productivity or to decrease it for pest control.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210100604
Funder
Australian Research Council
Funding Amount
$436,600.00
Summary
How do cells sense and react to mechanical forces? There is accumulating evidence that mechanical forces exerted on tissues and cells strongly influences their behaviour. My research aims to understand how cells sense and respond to forces experienced throughout life. Using a combination of three-dimensional cell and tissue culture methods, I will investigate how compressive forces change the biochemistry of cells and their functionality. This work is aimed at generating fundamental knowledge to ....How do cells sense and react to mechanical forces? There is accumulating evidence that mechanical forces exerted on tissues and cells strongly influences their behaviour. My research aims to understand how cells sense and respond to forces experienced throughout life. Using a combination of three-dimensional cell and tissue culture methods, I will investigate how compressive forces change the biochemistry of cells and their functionality. This work is aimed at generating fundamental knowledge to improve our comprehension of how cells respond to force. The expected outcome is a greater understanding of mechanical and biochemical relationships between cells and the environment, to inform fields of tissue engineering of culture scaffolds to better mimic natural cell-tissue settings.Read moreRead less
Regulation of cell proliferation and survival by the ubiquitin system. This project aims to investigate how the fundamental processes of cell division and cell death are controlled at the molecular level by protein degradation enzymes (known as ubiquitin ligases), and how these regulate cellular homeostasis. Using interdisciplinary approaches incorporating proteomics, biochemistry, and molecular cell biology, this project seeks to delineate the components of signalling pathways implicated in the ....Regulation of cell proliferation and survival by the ubiquitin system. This project aims to investigate how the fundamental processes of cell division and cell death are controlled at the molecular level by protein degradation enzymes (known as ubiquitin ligases), and how these regulate cellular homeostasis. Using interdisciplinary approaches incorporating proteomics, biochemistry, and molecular cell biology, this project seeks to delineate the components of signalling pathways implicated in the degradation of proteins implicated in cell division and cell death. Expected outcomes include an increased understanding of how proteins are specifically selected for degradation. Protein degradation pathways operate with remarkable selectivity and this work is expected to illuminate the mechanisms of substrate targeting. The biochemical approaches will provide insight and impact in the areas of cell signaling, organelle biology and cell biology.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100011
Funder
Australian Research Council
Funding Amount
$900,000.00
Summary
Integrated Multimodal System for Multiplexed Imaging of Signal Transduction. This project will introduce a unique microscopy platform and associated technologies into the Australian research environment that will enable researchers to redefine our understanding of molecular signal transduction. The instrumentation will enable the multidimensional imaging of live cells with unprecendented speed and sensitivity. The featured imaging modalities will enable the integration of distinct biological, ....Integrated Multimodal System for Multiplexed Imaging of Signal Transduction. This project will introduce a unique microscopy platform and associated technologies into the Australian research environment that will enable researchers to redefine our understanding of molecular signal transduction. The instrumentation will enable the multidimensional imaging of live cells with unprecendented speed and sensitivity. The featured imaging modalities will enable the integration of distinct biological, biochemical and chemical probes with a focus on minimizing phototoxicity. Expected outcomes include new fundamental knowledge on molecular signal transduction and cell heterogeneity; development of novel probes and methodologies and the development of new and existing interdisciplinary research collaborations. Read moreRead less