Understanding the factors that control T cell responses has been a major focus of immunology. Despite this effort the factors that control T cell development, homeostasis and function are still only incompletely understood. Accordingly we have been studying the TNF-family cytokine BAFF (B cell activation factor of the TNF-family) in relation to T cell behaviour and function. Though BAFF was first described as being critical for B cell development and maturation, a number of lines of evidence ind ....Understanding the factors that control T cell responses has been a major focus of immunology. Despite this effort the factors that control T cell development, homeostasis and function are still only incompletely understood. Accordingly we have been studying the TNF-family cytokine BAFF (B cell activation factor of the TNF-family) in relation to T cell behaviour and function. Though BAFF was first described as being critical for B cell development and maturation, a number of lines of evidence indicate that BAFF may be important in T cell biology. Current studies suggest that BAFF exerts a pro-inflammatory effect upon T cell responses. Surprisingly then, when we examined the role of BAFF upon T cell function in vivo in the context of the allo-immune response, we found that ~60% of BAFF transgenic mice failed to reject a fully-mismatched allograft. Intriguingly, BAFF transgenic mice exhibited an increased number of CD4+ CD25+ Foxp3+ cells in the periphery and in vivo depletion of these CD25+ cells restored the ability of BAFF transgenic mice to reject an allograft. We hypothesize that BAFF plays a potentially powerful anti-inflammatory role in regulating certain T cell dependent immune responses. Our data suggests that BAFF can modulate T cell function by effecting T cell regulation.Read moreRead less
Cellular Mechanisms Of Functional Deficits In Experimental Glaucoma
Funder
National Health and Medical Research Council
Funding Amount
$294,541.00
Summary
If successful, our approach will potentially have a major impact on the treatment of diabetic retinopathy and possibly on all diabetic vascular diseases. A single injection might only be necessary to prevent the development of diabetic retinopathy, which would represent a significant weapon in the management of patients. In addition, successful application of secretion gene therapy in the eye might open up the possibility to introduce the same concept for the treatment of larger organs undergoin ....If successful, our approach will potentially have a major impact on the treatment of diabetic retinopathy and possibly on all diabetic vascular diseases. A single injection might only be necessary to prevent the development of diabetic retinopathy, which would represent a significant weapon in the management of patients. In addition, successful application of secretion gene therapy in the eye might open up the possibility to introduce the same concept for the treatment of larger organs undergoing microvascular changes as a result of diabetes.Read moreRead less
Abnormal growth of blood vessels is a central feature of number of blinding conditions of the eye. Although there are treatments available that reduce the sudden loos of vision in a majority of people with advanced age related macular degeneration, about 20% fail to respond and half gradually loose vision. This project will determine the effectiveness of treating vascular diseases of the retina with a novel therapy that is quite different to that currently available.
Dynamic Trafficking Of Amino Acid Transporters At Synapses And Their Role In Regulating Neurotransmission
Funder
National Health and Medical Research Council
Funding Amount
$421,219.00
Summary
Brain cells release chemical neurotransmitters to activate their neighbours. The most abundant neurotransmitter is glutamate, which mediates most of the communication in the brain. Following release, this neurotransmitter must be rapidly recycled to prevent levels being depleted and neurotransmission failing. The subject of this grant is to understand what molecules and pathways are used to recycle glutamate in the brain, and how its supply is controlled to sustain continual brain activation.