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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.
Mechanisms Of Regulating Gene Expression Via Selective MRNA Transport
Funder
National Health and Medical Research Council
Funding Amount
$424,076.00
Summary
A critical step in the gene expression pathway that is altered in cancer is nuclear export of mRNA. We have demonstrated that mRNA export is not constitutive, but highly selective and can regulate distinct biological processes through poorly understood mechanisms. This project aims to dissect the molecular mechanisms of regulating gene expression via selective mRNA transport. This will establish selective mRNA export as a novel area of research in cancer biology.
The cell is the building block of life. This proposal focusses on the surface of the cell, the plasma membrane, and specialised structures called caveolae that are an abundant feature of animal cells. Altered caveolae are a feature of many human disease conditions. In this proposal we will address the function of caveolae. We will test the idea that proteins are released from caveolae into the cell when cells are stressed forming a novel signalling pathway disrupted in disease.
Defining The Role Of A Palmitoylated Variant Of Sphingosine Kinase 1 In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$603,452.00
Summary
Sphingosine kinase is a protein that when dysregulated is involved in cancer development and progression. We have recently made a substantial breakthrough in this area by identifing a naturally occuring variant of sphingosine kinase that is constantly activated and has an enhanced ability to induce cancer. In this study we will examine and target this form of sphingosine kinase as a potential therapeutic intervention in cancer.
Retinoic Acid Receptor-related Orphan Receptors And The Regulation Of Metabolism:insights Into Diabetes And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$760,799.00
Summary
Nuclear receptors (NRs) function as hormone dependent DNA binding proteins important in sustaining human health, highlighted by the array of medicines that target these proteins for human well being. ROR alpha is one such protein that we have shown regulates fat mass, obesity, and glucose tolerance. Obesity and diabetes are often linked with inflammation. We will examine how ROR controls inflammation during metabolic disease.
Role Of Hsp40 And Hsp70 In Huntingtin Misfolding, Oligomerization And Inclusion Assembly
Funder
National Health and Medical Research Council
Funding Amount
$590,103.00
Summary
Huntington disease results from a mutation that causes the Htt protein to become abnormally sticky and form toxic clusters in neurons. Cells have natural defences to clustering with proteins called chaperones, which are exciting therapeutic targets. This project will examine how chaperones defend against toxic Htt clustering with cutting-edge imaging technologies. The knowledge gained will aid in designing therapeutic strategies that stimulate the defence processes and suppress the clusters.
Characterisation Of TIA Proteins In RNA Recognition And Stress Granule Formation
Funder
National Health and Medical Research Council
Funding Amount
$566,966.00
Summary
Cells in our body need to be able to respond to stresses such as heat, hypoxia, chemical stress or infection. In this project we investigate the specialized TIA proteins that have the job of protecting RNA in stressed cells. We will investigate the way TIA proteins recognize particular mRNA and form temporary protective clusters. By better understanding this process we will gain insight into the way in which cells are susceptible to damage in diseases including neurodegenerative disease.
DBHS Protein RNA Interactions In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$748,073.00
Summary
In cells involved in cancer, the interactions of DBHS proteins with each other, and with nucleic acids (eg RNA) are different to those in healthy cells. Only once we understand how DBHS proteins interact with some important RNA molecules, and how these interactions affect cell biology, can we begin to open up new pathways for therapy. This proposal aims at understanding and explaining this complex aspect of biology.
PCSK9 is an inhibitor of the receptor that is responsible for removing LDL (the bad cholesterol) from the circulation. We will study the molecular mechanisms that inhibit PCSK9 at the protein level. This study is needed to understand if drugs that inhibit PCSK9 will diminish the risk of developing heart disease in patients who do not respond well to existing treatments, for example those who already had a cardiovascular event or those with familial hypercholesterolemia.
The NF-kB Transcription Factors C-Rel And RelA Control Multiple Steps In Natural CD4 Regulatory T Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$566,592.00
Summary
An unfortunate consequence of immune function is that occasionally rogue immune cells are produced that attack the host and lead to the development of so-called autoimmune diseases such as arthritis. Normally a white blood cell called a regulatory T cell suppresses these self-reactive immune cells. We have identified factors that govern the generation of regulatory T cells. Understanding how these factors work should permit the development of new strategies to combat autoimmune diseases. ?