Molecular Interactions Of The Tetraspanins CD37, TSSC6 And CD151 In T Cells
Funder
National Health and Medical Research Council
Funding Amount
$566,575.00
Summary
The tetraspanins are a new type of protein that are found at the surface of cells. Cells of the immune system, such as white blood cells, display at their surface, up to 20 different tetraspanin proteins. However, the precise contributions of these tetraspanin proteins to immunity is still not clear, nor is it clear exactly how tetraspanin proteins differ from one another and why white blood cells need to display so many different tetraspanins. Using genetic technology we have created mice which ....The tetraspanins are a new type of protein that are found at the surface of cells. Cells of the immune system, such as white blood cells, display at their surface, up to 20 different tetraspanin proteins. However, the precise contributions of these tetraspanin proteins to immunity is still not clear, nor is it clear exactly how tetraspanin proteins differ from one another and why white blood cells need to display so many different tetraspanins. Using genetic technology we have created mice which are unable to express certain individual tetraspanin proteins at their cell surface. Excitingly, the immune systems of these mice are not normal, in particular one type of white blood cell, the T cell responds in an exaggerated manner to stimulation. These results suggest a role for tetraspanins in the control and regulation of the immune system. This project will extend these results and work out the precise molecular mechanism by which the tetraspanins exert this control. In the future, a full understanding of how tetraspanins control T cells may ultimately lead to novel ways of controlling the immune system.Read moreRead less
Dendritic cells are a very rare type of white blood cell which play a critical role in the initiation of the immune response. They are of particular interest to scientists interested in vaccination, as for a vaccine to work effectively, the vaccine must be presented to the rest of the immune system by the dendritic cell. It has only recently become apparent that there are several types of dendritic cell, and these different types of dendritic cell vary in their ability to present a vaccine to th ....Dendritic cells are a very rare type of white blood cell which play a critical role in the initiation of the immune response. They are of particular interest to scientists interested in vaccination, as for a vaccine to work effectively, the vaccine must be presented to the rest of the immune system by the dendritic cell. It has only recently become apparent that there are several types of dendritic cell, and these different types of dendritic cell vary in their ability to present a vaccine to the immune system. We have already identified some proteins that are expressed on the surface of only one type of dendritic cell. We will explore the possible use of these proteins as a means of delivering a vaccine to only one type of dendritic cell. This project will also identify new genes that are expressed in some types of dendritic cells but not others. These new genes whose expression does differ amongst the dendritic cells are potential targets for manipulating the immune system and ensuring more efficient vaccination.Read moreRead less
Investigation Of Early Cell Surface Rearrangements Mediating Adequate TCR-pMHC Engagement
Funder
National Health and Medical Research Council
Funding Amount
$303,708.00
Summary
This project aims to use advanced cell imaging techniques to view precise interactions that occur between cells as our immune system attacks and destroys infected cells. The techniques to be employed are highly advanced and involve cutting edge science. Essentially these techniques allow the production of movies of the body's immune system in action. Determining these interactions in such detail is important for understanding the body’s ability to fight infection.
Characterisation Of The Molecular Mechanisms Of Abeta-induced Proteolysis Of The Neural Cell Adhesion Molecule 2 (NCAM2)
Funder
National Health and Medical Research Council
Funding Amount
$374,666.00
Summary
Neurons in the brain are connected by synaptic contacts. Amyloid beta peptide accumulating in the brain in Alzheimer’s disease destroys synaptic contacts by degrading synaptic cell adhesion molecules which maintain the structure of the contacts. The aim of the project is to characterise the molecular mechanisms of amyloid beta-dependent degradation of synaptic cell adhesion molecules. The project will identify strategies that can be used to inhibit synapse loss in Alzheimer’s disease.
Identifying An Autism Gene Network Governing Stem Cell Division, Neurogenesis And Cortical Malformation
Funder
National Health and Medical Research Council
Funding Amount
$1,003,589.00
Summary
Failure to produce neural stem cells and new neurons in the embryonic cortex results in cortical malformations and autism, and thus has profound consequences for the individual's survival and quality of life. Here we explore how a unique network of autism proteins maintains stem cell activity and neuronal production, thereby ensuring the fidelity of cortical development.
I am a cell biologist investigating the means by which intracellular compartmentalization of signalling proteins determines signalling outcomes and cell fate. I focus particularly on signals that regulate immune function and cancer progression.
How The Dosage Of A Down Syndrome Candidate Gene Affects Neural Circuitry And Behaviour
Funder
National Health and Medical Research Council
Funding Amount
$414,961.00
Summary
In Down syndrome, an extra copy of chromosome 21 increases gene expression and leads to brain defects. We hypothesise that one candidate gene, Dscam2, changes its function with increased expression. This causes brain cells that normally stick to each other to repel each other, leading to inappropriate connections in the brain. We will test this model in the fruit fly and demonstrate for the first time a mechanism dependent on gene expression that can lead to brain abnormalities in Down syndrome.
Targeting The Hypoxia Sensing Pathway To Improve Hematopoietic Stem Cell Mobilisation And Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$653,313.00
Summary
Transplantation of patients’ own blood stem cells is used to treat many blood cancers. It increases the chance of cure. However the damage caused by chemotherapies used to combat the cancer can compromise stem cell collection and transplantation. Without transplant, these patients are less likely to survive cancer. This project is to test new drugs that enhance the harvest of blood stem cells for transplantation. These will increase the success rates of transplants and cure in these cancer patie ....Transplantation of patients’ own blood stem cells is used to treat many blood cancers. It increases the chance of cure. However the damage caused by chemotherapies used to combat the cancer can compromise stem cell collection and transplantation. Without transplant, these patients are less likely to survive cancer. This project is to test new drugs that enhance the harvest of blood stem cells for transplantation. These will increase the success rates of transplants and cure in these cancer patients.Read moreRead less
Functional Characterisation Of A New Surface Adhesion Molecule On Human Vascular Progenitor Cells To Combat Cancer
Funder
National Health and Medical Research Council
Funding Amount
$593,794.00
Summary
Collectively, diseases of the blood vascular system contribute immensely to the burden of health care in Australia. Notably, abnormal blood vessel formation is a major cause or contributor to many diseases, such as cancer, cardiovascular disease, rheumatoid arthritis, ischemia injury and diabetes. This project aims to understand the underlying mechanisms associated with aberrant angiogenesis such that it may aid in the identification of novel targets for the development of therapeutics.