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.
A New Master Adaptor Protein For Toll-like Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$869,288.00
Summary
Certain proteins on the surface of cells are able to sense danger and infection. These receptors use adaptor proteins to enable cells to respond appropriately. We have discovered a new adaptor that controls receptor signalling in inflammation. This new master adaptor likely has widespread roles in infection and inflammation. We aim to understand how this adaptor works, and to identify ways of blocking its actions. These studies may help us to control inflammation underpinning many diseases.
Identifying Novel Genome Instability Signatures In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$320,891.00
Summary
Cancer is the single biggest clinical problem facing the world. An underlying hallmark of cancer is the accumulation of errors in the genetic information of a cell which arises through genomic instability. This research project aims to investigate novel molecules identified by our screening that function in response to genomic instability in cancer. This study is expected to define roles for each molecule in the maintenance of genomic stability and predict for patient diagnosis and outcome.
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.
Integrating Wnt-Apc Pathway With TGF-beta Signalling In Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$342,364.00
Summary
Colon cancer is one of the leading causes of death of all cancers. Two molecular pathways have been independently implicated in colon cancer development. Emerging evidences suggest that the two pathways may work together in the colon polypus formation. This application will integrate two separate molecular causes to form a new coherent understanding of cancer development and offer new directions in development of novel colon cancer treatment.
After infection with viruses, parasites and bacteria the protein SerpinB2 becomes very abundant in macrophages, which are white blood cells involved in inflammation. Unfortunately, what this protein is doing is very unclear. We have found that macrophage SerpinB2 dampens the responses of other immune cells. This grant aims to determine how this is achieved and thereby help resolve the role of this protein in a number of diseases such as cancer, lupus, asthma and pre-eclampsia.
Profiling Global Inflammatory Signatures For GPCRs In Human Macrophages
Funder
National Health and Medical Research Council
Funding Amount
$687,770.00
Summary
Macrophages are important white blood cells of the immune system. They trigger inflammatory responses to infection or injury, but prolonged inflammatory responses can lead to chronic diseases. In this project we aim to better understand how macrophages sense the outside environment, how external signals trigger inflammatory processes, how this leads to diseases such as autoimmune and inflammatory diseases, cancer and cardiovascular diseases, and how to control them with drugs.
Histone deacetylase functions in immune cells. This project aims to define how an enzyme (a histone deacetylase) enables innate immune cells (macrophages) to respond to specific danger signals, such as those activating Toll-like Receptors. To identify processes that provide specificity to signal transduction pathways, this project will characterise protein targets and biological functions of a specific class IIa histone deacetylase in macrophages. This project expects to result in an understandi ....Histone deacetylase functions in immune cells. This project aims to define how an enzyme (a histone deacetylase) enables innate immune cells (macrophages) to respond to specific danger signals, such as those activating Toll-like Receptors. To identify processes that provide specificity to signal transduction pathways, this project will characterise protein targets and biological functions of a specific class IIa histone deacetylase in macrophages. This project expects to result in an understanding of histone deacetylases and protein deacetylation in immune cell responses which can be harnessed to manipulate cell functions for basic science and biotechnology uses.Read moreRead less
Regulation of mRNA translation by the microtubule-associated protein Tau. This project aims to understand the molecular processes in a cell type and subcellular compartment that underlies learning and memory formation. Fundamental neuronal functions such as synaptic strengthening and memory formation are dependent on the tightly regulated process of protein translation. The kinase Fyn (which is localised to dendritic spines where memories are formed) activates the ERK/S6 pathway leading to massi ....Regulation of mRNA translation by the microtubule-associated protein Tau. This project aims to understand the molecular processes in a cell type and subcellular compartment that underlies learning and memory formation. Fundamental neuronal functions such as synaptic strengthening and memory formation are dependent on the tightly regulated process of protein translation. The kinase Fyn (which is localised to dendritic spines where memories are formed) activates the ERK/S6 pathway leading to massive translation of the scaffolding protein Tau. More importantly, the activation of this cascade is Tau-dependent. This project aims to determine how Tau activates this pathway, and to decipher the physiological role of the Tau/Fyn/Tau feedback loop. This will inform our understanding of the molecular regulation of learning and memory.Read moreRead less