The Regulation Of Pleiotropic Responses By Bidentate Motifs Embedded In The Fibroblast Growth Factor Receptors
Funder
National Health and Medical Research Council
Funding Amount
$489,336.00
Summary
Cells in our bodies are able to accomplish an impressive array of functions. Diffusible factors (called growth factors) are important in regulating diverse cellular functions. We have identified a new molecular switch inside cells that acts as a master controller of cellular functions. This molecular switch relays information to instruct specific cellular functions. We have shown that these molecular switches are short-circuited in breast cancer promoting cell growth and survival.
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.
Macrophages are important cells at the front-line of immunity where one of their main roles is to release anti-bacterial proteins. We will study the macrophage molecules, subcellular organelles and pathways that help to release these proteins to kill bacteria and fight infection. Our studies will identify new cellular targets for boosting immunity and treating inherited diseases with defective macrophage function.
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.
Function Of Factor H-related Protein-5, A Novel Human Plasma Complement Protein Found In Glomerular Immune Deposits
Funder
National Health and Medical Research Council
Funding Amount
$186,430.00
Summary
The Investigators have recently discovered a new protein which is present in human blood and is also seen in the diseased kidneys of patients with nephritis. The new protein is present in all types of nephritis that are caused by antibodies together with another part of the immune system, called the complement system, which is know to have an important role in causing tissue damage in immune diseases. The new protein is a part of the complement system but its exact function is not yet known. The ....The Investigators have recently discovered a new protein which is present in human blood and is also seen in the diseased kidneys of patients with nephritis. The new protein is present in all types of nephritis that are caused by antibodies together with another part of the immune system, called the complement system, which is know to have an important role in causing tissue damage in immune diseases. The new protein is a part of the complement system but its exact function is not yet known. The protein is likely to be important in immune diseases because it is so commonly found in diseased kidneys and other organs with complement-associated disease. In this project we will conduct a series of experiments which will determine how the new protein works in the complement system and also how important the protein is in causing kidney damage in nephritis. Nephritis is the commonest cause of kidney failure in Australia and research directed towards the mechanism of kidney damage has the potential to produce new types of therapy. The complement system also has a major role in other inflammatory diseases and in body defense systems (such as protection against microbial attack). The complement system must be able to distinguish between foreign particles and the body's own tissue and this new protein may have a role in the appropriate regulation of complement to attack the right things in the body. Elucidation of the function of this protein may well assist, therefore, in developing therapies for a variety of inflammatory diseases and infectious diseases, in addition to nephritis.Read moreRead less
The Regulation Of Pleiotropic Responses By Phospho-Ser/Tyr Binary Switches Embedded In Growth Factor Receptors
Funder
National Health and Medical Research Council
Funding Amount
$349,190.00
Summary
Cells in the body are able to accomplish an impressive range of functions within their lifetime. Underlying this diversity in cellular functions are a quorum of fundamental cellular responses that include cell survival, cell proliferation (growth) and cell differentiation (commitment to a more mature cell identity). Diffusible factors (called growth factors) are important in regulating these cellular responses. This is achieved through growth factor binding to specific proteins (called receptors ....Cells in the body are able to accomplish an impressive range of functions within their lifetime. Underlying this diversity in cellular functions are a quorum of fundamental cellular responses that include cell survival, cell proliferation (growth) and cell differentiation (commitment to a more mature cell identity). Diffusible factors (called growth factors) are important in regulating these cellular responses. This is achieved through growth factor binding to specific proteins (called receptors) on the surface of cells which in turn activate signalling cascades that convey messages within the cell instructing a specific response. We have identified a new mechanism that allows a growth factor receptor to convert analogue inputs (in the form of growth factor stimulation) to a digital output (where a cell responds in a decisive fashion). This analogue-to-digital conversion is encoded by a molecular switch embedded in growth factor receptors that toggles between two alternate positions to promote either cell survival alone or cell survival as well as cell differentiation-proliferation. In this manner, these molecular switches have binary (either-or) characteristics and provide a new explanation for the independent regulation and coordination of different cell functions. These findings have implications for understanding how specific cellular responses such as cell survival, proliferation and differentiation can be regulated and perhaps harnessed to improve tissue regeneration after damage (e.g. in stroke, heart attack trauma) or in understanding how things go wrong in diseases such as cancer where cell survival, proliferation and differentiation become deregulatedRead moreRead less