The Regulatory Role Of Clec12A In Antigen Presentation And Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,381,077.00
Summary
The immune system maintains a balance between initiating immune responses to infections and suppressing immune responses in health. We have identified, on the surface of specialised immune cells, a protein that is critical for regulating immune responses and dampening down inflammation. This proposal aims to determine how this protein functions in health and under inflammatory conditions, and to develop approaches based on its molecular interactions to reduce inflammatory disease.
Molecular Basis For The Efficient Processing Of Antigens Taken Up By Clec9A, A DAMP Receptor On Dendritic Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,302,392.00
Summary
Dendritic cells (DC) of the immune system utilise specific receptors to sense danger signals from their environment. We identified a DC danger receptor, Clec9A, which recognizes and induces immunity to “dangerous” dead cells eg. infected cells or killed tumour cells. We will investigate how DC use Clec9A to process “dangerous” dead cells, and the factors that control the potency of this immune response. This will enable us to develop novel immunotherapies for infectious diseases and cancer.
Enhancing Vaccine Efficacy By Harnessing Dendritic Cell Receptors And Their Unique Properties
Funder
National Health and Medical Research Council
Funding Amount
$687,519.00
Summary
Potent vaccination might be achieved by using monoclonal antibodies as magic bullets to target vaccines to special cells in the body. We show that targeting these special cells by using monoclonal antibodies that recognise Clec9A is effective, perhaps because it brings several different immune cells together so that they orchestrate very efficient immune responses. This application investigates how targeting Clec9A allows strong vaccination so that we can apply this to new generation vaccines.
The Role Of Membrane Condensation In T Lymphocyte Activation And Signal Transduction
Funder
National Health and Medical Research Council
Funding Amount
$82,421.00
Summary
T cell lymphocytes are essential cells in our immune system. They respond to signals from foreign bodies to mount an immune response. Many diseases arise from errors in their activation processes. The key steps in the translation of the initial arrival of a foreign-body to a T cell into an immune response will be examined in these studies, where we will look at the cooperation of components of the cell membrane during T cell activation. This will help us to understand and treat immune disorders.
Molecular Characterisation Of The Dendritic Cell Receptor Clec9a And Its Ligand Interactions
Funder
National Health and Medical Research Council
Funding Amount
$651,784.00
Summary
The immune system senses danger from infectious diseases, damaged and dead cells. We identified a danger receptor, Clec9A, on a specialised cell type of the immune system in mice and humans. Clec9A recognizes and induces immunity to dangerous dead cells. Delivering vaccines to Clec9A improves vaccine responses. We will investigate how Clec9A recognises and reacts to danger, and how we can mimic this recognition to improve vaccine design.
Regulation Of Mesenchymal Stem Cell Paracrine Activity In Post-myocardial Infarction Cardiac Repair
Funder
National Health and Medical Research Council
Funding Amount
$73,212.00
Summary
Heart failure remains to be a major cause of morbidity in Australian population. After myocardial infarction, the damaged heart undergoes a series of compensatory adjustments to maintain the workload, termed cardiac remodeling. The resultant beneficial response in the short term eventually becomes deleterious. Using adult stem cells, the project aims to develop a better treatment to manipulate the progression of such responses and prevent hearts from entering the end stage heart failure.
CD300f As A Novel Therapeutic Antibody Target In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$89,926.00
Summary
This study aims to develop a new antibody therapy for Acute Myeloid Leukaemia (AML), the most common type of leukaemia in adults. We will study the function of CD300f, a new receptor found on the surface of both healthy blood cells and the cancer cells in AML. We will investigate whether blocking this receptor with a newly developed antibody can be used to kill cancer cells. It is hoped that this study will allow development of this antibody for use in a future clinical trial.
Cells of the immune system need to recognise characteristic viral and bacterial molecules, in order to identify infection. Some immune cells can detect the presence of viral and bacterial DNA. The cells respond by making a number of anti-viral or anti-bacterial molecules, as well as activating other cells to fight the infection. The effect of bacterial DNA can be mimicked by certain short synthetic pieces of DNA. The potent activity of this synthetic DNA (termed CpG DNA ) is being exploited in a ....Cells of the immune system need to recognise characteristic viral and bacterial molecules, in order to identify infection. Some immune cells can detect the presence of viral and bacterial DNA. The cells respond by making a number of anti-viral or anti-bacterial molecules, as well as activating other cells to fight the infection. The effect of bacterial DNA can be mimicked by certain short synthetic pieces of DNA. The potent activity of this synthetic DNA (termed CpG DNA ) is being exploited in a number of clinical trials for treatment of cancer and allergy, as well as to improve vaccinations. Despite the rapid advance towards clinical application, there is still much basic information to learn about how CpG DNA acts on cells. The molecule to which DNA binds in order to activate the cells is called TLR9. TLR9 is not on the surface of cells, but within cells. In a bacterial infection, cells called macrophages engulf and digest bacteria and release the bacterial DNA within the cell, where it binds to TLR9. In other cases, including when CpG DNA is used therapeutically, the DNA needs to be taken up into the cell. Evidence shows that there is a receptor on the cell surface which binds DNA, and takes it into the cell. In this project we propose to identify this DNA uptake receptor. Apart from the use of CpG DNA, there are a number of other proposals for the therapeutic use of DNA. Although it is known that DNA enters into cells, the route for this has not been established. Whilst CpG DNA can activate immune cells, some other distinct DNA molecules can prevent the activation. We will examine whether these inhibitory DNA molecules bind more effectively to TLR9 than the CpG DNA, but do not activate the cell. These inhibitory molecules are proposed as a therapy for the autoimmune disease lupus, which involves inappropriate responses to DNA, and is thought to involve TLR9. In order to develop therapies, a detailed knowledge of how they work is essential.Read moreRead less