The Structure And Composition Of The T-cell Receptor-CD3 Complex
Funder
National Health and Medical Research Council
Funding Amount
$434,644.00
Summary
Our research will provide a fundamental advance in our understanding of how foreign viruses and pathogens trigger the immune system. Gaining a greater understanding of these central events will facilitate the design of novel therapies to treat immune associated disorders such as transplant rejection, autoimmune disease and some cancers.
The Structure And Composition Of The T-Cell Receptor-CD3 Complex
Funder
National Health and Medical Research Council
Funding Amount
$419,180.00
Summary
My research will use cutting edge imaging techniques to provide a fundamental advance in our understanding of how foreign viruses and pathogens trigger the immune system. Gaining a greater understanding of these central events will facilitate the design of novel therapies to treat immune associated disorders such as transplant rejection, autoimmune disease and some cancers.
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
Determining The Structure Of A Soluble Cytokine Receptor Complex
Funder
National Health and Medical Research Council
Funding Amount
$509,017.00
Summary
There is a pressing need to develop improved therapeutics to treat many forms of cancer and respiratory diseases. This proposal concerns the biochemical investigation of a group of protein hormones and their associated receptors that are implicated in blood cell cancers and for which current treatments are only partly effective . Our work will focus on determining the 3-dimensional shape and function of this group of proteins in complex with one another which will provide us with an understandin ....There is a pressing need to develop improved therapeutics to treat many forms of cancer and respiratory diseases. This proposal concerns the biochemical investigation of a group of protein hormones and their associated receptors that are implicated in blood cell cancers and for which current treatments are only partly effective . Our work will focus on determining the 3-dimensional shape and function of this group of proteins in complex with one another which will provide us with an understanding of how these proteins communicate with one another. This information may provide a basis for the design of new drugs that can specifically block the activity of these protein hormones, thereby providing new treatment possibilities for these blood cell cancers.Read moreRead less