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.
Elucidating Crosstalk Between RhoGTPases And Polarity Proteins: The Interface Between Morphology, Immune Function And Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$627,549.00
Summary
Major breakthroughs in cancer and autoimmunity require understanding the molecular basis of by which cell behaviour is controlled. We now know the key molecular players, but still need to determine how they interact within the cell to develop the best treatments and diagnostics. Recent breakthroughs now enable us to “watch” molecular interactions within the cell. We will use these approaches to determine how a key molecular switch is regulated in immune cells and cancer cells.
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.
Biology Of EGFR Mutations In Glioblastoma Multiforme
Funder
National Health and Medical Research Council
Funding Amount
$287,445.00
Summary
The epidermal growth factor receptor (EGFR) is a protein that has a critical role in the development of normal cells. In glioma, the most lethal of the brain cancers, the EGFR is altered. These alterations result in uncontrolled activation of the EGFR, causing signals that promote the growth and survival of brain cancer. This grant seeks to understand the nature of the signals mediated by the altered EGFR, in turn helping us develop better therapeutics for the treatment of this deadly cancer.
Structure-function Of Type I Interferon Receptors: Informing The Basis For Selective Modulation Of Signal Transduction And Function
Funder
National Health and Medical Research Council
Funding Amount
$1,316,153.00
Summary
Interferons (IFNs) are a family of proteins with critical roles in infectious and inflammatory diseases and cancers. Currently we do not understand why there are so many type I IFNs, their different functions and how they are achieved. This project will determine at a fine molecular level how different IFNs interact with molecules on target cells and transmit particular signals. We will focus on a novel IFN? that we discovered. These studies will underpin the development of new therapies.
Understanding The Role Of The Atypical Cadherin Fat4 In Lymphatic Vascular Development
Funder
National Health and Medical Research Council
Funding Amount
$1,006,248.00
Summary
This application will define the role of a large cell adhesion molecule, FAT4, in lymphatic vascular development. By understanding how FAT4 functions in lymphatic vessels, we will gain insight to the mechanisms by which mutations in the gene that encodes this protein cause a human lymphoedema syndrome.
Characterising The Novel Signalling Mechanism For A New Interferon
Funder
National Health and Medical Research Council
Funding Amount
$525,485.00
Summary
We have discovered a new regulatory protein called interferon epsilon, made in the female reproductive tract and is crucial for protection against bacterial( Chlamydia) and viral (Herpes Simplex Virus) infections. However, we are yet to understand how it interacts with target cells. This grant will study how IFN? binds to cells and the nature of the signals it transmits. This will help us understand its role in disease and its clinical potential
Target Of Rapamycin control of nutrient uptake. This project aims to study nutrient uptake in eukaryotes. It is expected to generate new knowledge of critical and conserved features of environmental and Target Of Rapamycin (TOR)-mediated control of nutrient uptake, specifically endocytosis, building on novel preliminary data that identifies novel TOR control points. The expected outcomes include new insights into mechanisms controlling nutrient uptake and fostering institutional collaboration. T ....Target Of Rapamycin control of nutrient uptake. This project aims to study nutrient uptake in eukaryotes. It is expected to generate new knowledge of critical and conserved features of environmental and Target Of Rapamycin (TOR)-mediated control of nutrient uptake, specifically endocytosis, building on novel preliminary data that identifies novel TOR control points. The expected outcomes include new insights into mechanisms controlling nutrient uptake and fostering institutional collaboration. This knowledge is highly relevant to any industry or research project utilising living organisms, as nutrient availability supports survival, cell growth and proliferation.Read moreRead less