Determining Regulators Of ILC3 In Mucosal Barrier Function And Immune Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$705,209.00
Summary
Innate lymphoid cells (ILCs) are specialized cells that defend the body against invading microorganisms at the body’s surfaces, mediate pathogen clearance and tissue repair but may also drive inflammatory conditions such as allergic asthma and inflammatory bowel disease. We will investigate the molecular switches that regulate this novel cell type and potentially uncover novel molecules or pathways for therapeutic targets.
Deciphering The Role Of Intron Retention In Monocyte Differentiation And Function
Funder
National Health and Medical Research Council
Funding Amount
$511,114.00
Summary
In 2013, we made a breakthrough discovery that certain parts of genes, previously considered “Junk DNA”, are actually carrying signals to control the amount of proteins produced in cells. We now wish to understand the roles of these signals in the development of a key immune cell called monocyte. Monocytes are important to fight infection and inflammation in diseases such as diabetes and cancer. We hope to advance our knowledge on how we can manipulate these cells for therapeutic gain.
Functional Assessment Of CD40 In The Development Of Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$521,910.00
Summary
Many of the genes which affect susceptibility to Multiple Sclerosis (MS) have recently been identified. Two of these genes were first discovered in an Australian study published in Nature Genetics in 2009. One of these is CD40, which controls immune cell activation. In this project we aim to establish how the genetic variant identified affects the function of the CD40 gene in MS. CD40 may prove to be a good therapeutic target, with agents available to modulate CD40 available already.
Control Of Immunoreceptor Assembly And Function By Intramembrane Sequence Elements
Funder
National Health and Medical Research Council
Funding Amount
$403,121.00
Summary
The cells of the immune system constantly survey their environment for changes that indicate damage. To sense their surroundings cells employ a host of receptors that are associated with signalling adapter proteins that initiate signalling cascades inside the cell when receptors bind ligands. This project seeks to determine the structural mechanisms of signal propagation across the plasma membrane of immune cells.
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.
Validation Of PAG1 As A New Risk Gene With Therapeutic Potential For Asthma
Funder
National Health and Medical Research Council
Funding Amount
$687,436.00
Summary
About 10% of adults and children suffer from asthma in Australia. For >60% of these their asthma symptoms are not well controlled with existing treatments and so novel therapies are needed. We have recently identified PAG1 as a novel risk gene for asthma. In this study, we will conduct mouse and human studies to investigate the possibility inhibition of PAG1 might help prevent or treat asthma exacerbations.
Correlating Multiple Sclerosis Risk SNPs With Immune Cell Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$789,386.00
Summary
In Multiple Sclerosis (MS), the immune system repeatedly attacks the brain and spinal cord. In the last three years, rapid progress has been made in understanding genetic risk factors for MS, and more than 20 are known, but their function is not understood. The proposed study will recruit patients with MS and healthy controls to isolate five major immune cell types, and will assess how risk genes influence these cells. We hope to obtain a much better picture of how genetic risk factors for MS ac ....In Multiple Sclerosis (MS), the immune system repeatedly attacks the brain and spinal cord. In the last three years, rapid progress has been made in understanding genetic risk factors for MS, and more than 20 are known, but their function is not understood. The proposed study will recruit patients with MS and healthy controls to isolate five major immune cell types, and will assess how risk genes influence these cells. We hope to obtain a much better picture of how genetic risk factors for MS actually work.Read moreRead less
Cytotoxic T Lymphocyte Synapse Formation And Serial Killing: When Breaking Up Is Hard To Do.
Funder
National Health and Medical Research Council
Funding Amount
$626,688.00
Summary
Killer T cells are a specialised group of immune cells, which destroy cancerous and infected cells. When killer T cells find a target, they attach and secrete toxic molecules. It then detaches from the dying target, so that it may go on to kill other cells. If it doesn’t detach properly, it remains bound to the target cell and results in an improper immune response. This proposal will investigate how the killer cell detaches, which is essential for an efficient immune response.
Interleukin Signalling In CD4+ T Cell Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$663,919.00
Summary
Our bodies rely on the production of antibodies to fight infection. The cytokine IL-21 is produced by immune cells called T follicular helper (Tfh) cells that help B cells make antibodies. Tfh cells, in turn, are controlled by regulatory (Tfr) cells. Our findings demonstrate that IL-21 supports Tfh cells and limits Tfr cells, thus favoring antibody production and long term immunity. Using genomic and cellular approaches, the mechanism(s) underlying these observations will be explored.
Analysis Of Human CD4+ T-cell Responses To Epitopes Formed By Peptide Fusion In The Pathogenesis Of Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$1,239,989.00
Summary
Type 1 diabetes is caused by immune-mediated destruction of the insulin-secreting beta cells. Recently we discovered new targets ‘seen’ by the immune system that may explain why the immune system causes type 1 diabetes. Here we will determine if responses to these targets cause type 1 diabetes. This is important because it tests a new idea and our results will have a major impact on efforts to develop new therapies for type 1 diabetes an other autoimmune diseases.