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.
Treating and preventing painful fractures could be improved by strengthening cortical bone – the hard outer shell of all bones in the skeleton. We don’t know how cortical bone forms, but if we did, we could improve its strength. We have found that a brain-like network of cells inside the skeleton, called osteocytes, use a specific signal, called SOCS3, to make strong cortical bone. This study will find out how SOCS3 works and find new ways to make cortical bone strong and healthy.
This Program studies the mechanisms that control blood cell formation and how abnormalities play a role in leukaemia, a significant health problem worldwide. Despite some improvements, two major problems remain: controlling progression of leukaemia and relapse. The Program tackles these two major issues with the combination of studies of normal blood and leukaemia cell function, drug design and clinical trials ensuring a direct pathway from discovery to patient benefit.
Cellular Regulation Of Receptor Signalling And Cytokine Responses
Funder
National Health and Medical Research Council
Funding Amount
$859,288.00
Summary
Cell surface receptors and signalling pathways elicit the release of cytokines, or chemical messengers, to control inflammation, which is the body’s response to infection or danger. We have discovered a new signalling pathway that can turn off inflammation and help prevent inflammatory disease. Our studies will now define the molecular details of this pathway and show how new and existing drugs targeting this pathway can be optimally used to treat inflammation and cancer.
Genetic Validation Of Stat3 As A Tractable Pharmacological Target In Gastrointestinal Disease
Funder
National Health and Medical Research Council
Funding Amount
$586,964.00
Summary
Cancers of the stomach and the colon are a major health burden. One of the central signaling molecules that drives these cancers is called Stat3. Here we propose to use a novel strain of mice that allows us to experimentally dial down the amount of Stat3 protein and hence to predict how effective a future anti-Stat3 cancer drug will be.
Mechanisms Of Cytokine Independence During The Development Of Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$598,163.00
Summary
Signals from growth factors such as cytokines and hormones are required for cell survival. In their absence cells activate an in-built self-destruct process. Determining how cytokines regulate cell death will provide novel targets so that unwanted cells (like cancer cells) can be triggered to die and needed cells (such as brain cells) can survive.
Targeting The Interface Between Tumours And Their Microenvironment For The Treatment Of Gastrointestinal Cancers
Funder
National Health and Medical Research Council
Funding Amount
$785,045.00
Summary
This fellowship explores the synergistic interactions between intestinal cancer cells and the tumour microenvironment and which promote survival, expansion, migration and invasion as well as facilitating the development of resistance to anti-cancer therapy. Aided by the clinical expertise of my collaborators, my efforts are likely to yield translational outcomes, including the development of therapeutic IL-11 antagonists, and of a serum protein signature indicative of early stage gastric cancer.