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
Discovering Molecular Signatures Of Human T Follicular Helper Cells And Antibody Producing B Cells To Improve Vaccine Efficacy And Transplation Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
A key way the body can fight off infections is to produce antibodies, a process that requires the coordinated efforts of multiple types of specialised immune cells. A more detailed understanding the factors that govern robust antibody responses is critically needed and will be investigated in this project in the context of vaccination and transplant rejection.
Tracking The Impact Of Superinfection With A Common Herpesvirus On T Cell Immunity In Humans
Funder
National Health and Medical Research Council
Funding Amount
$317,775.00
Summary
Human herpesviruses, including cytomegalovirus, infect the vast majority of people and can cause serious complications in healthy people and in immune suppressed transplant patients. The development of vaccines to treat herpesvirus infections remain a signficant priority. However it is not known what impact repeated exposure to different strains of these viriuses has upon immunity. This study will investigate the impact of exposure to different strains of cytomegalovirus on immunity in healthy i ....Human herpesviruses, including cytomegalovirus, infect the vast majority of people and can cause serious complications in healthy people and in immune suppressed transplant patients. The development of vaccines to treat herpesvirus infections remain a signficant priority. However it is not known what impact repeated exposure to different strains of these viriuses has upon immunity. This study will investigate the impact of exposure to different strains of cytomegalovirus on immunity in healthy individuals and transplant patients.Read moreRead less
My research is aiming to study how the immune system controls viral infections in transplant patients and use this information to bolster their immunity in a test tube, providing protection against a virus the patient is unable to fight after their transplant. We are also trying to develop new strategies to use patient's own blood cells which will be grown in the laboratory and returned to the patient, resulting in a full recovery.
Transcriptional Regulation Of Hematopoietic Commitment
Funder
National Health and Medical Research Council
Funding Amount
$289,985.00
Summary
Blood cell formation is a tightly regulated process and provides an important model for our understanding of blood homeostasis. Perturbations result in a number of disorders such as leukaemia. The application of stem cells to many diseases is being pursued; yet, to be successful knowledge of normal cellular behavior is crucial. I aim to improve our understanding of these processes and help to provide the framework for future studies aimed at more directly manipulating blood cell functions.
This research aims to understand the early developmental events in human blood cell diversi?cation that generate cells involved in oxygen transport, wound healing and protecting us from cancer and infection. The ?ndings will assist in diagnosing and treating human immune system and blood cell disorders such as leukaemia, chronic infection and autoimmunity through understanding the mechanisms of how normal, healthy blood cells are generated.
Mapping The Steps And Deciphering The Mechanisms Crucial In Dendritic Cell Development.
Funder
National Health and Medical Research Council
Funding Amount
$582,064.00
Summary
Dendritic cells (DCs) are a type of white blood that kick-start immune responses. There are various types of DCs that specialize in, for example, clearing viral, bacterial or fungal infections, and are even used to fight cancer. Understanding how DCs grow, therefore, has many clinical benefits. This project aims to understand these processes and identify new regulators of their growth using cutting edge technologies and strategies.
Role For Sphingosine Kinase-1 In Endothelial Progenitor Cell Survival And Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$294,205.00
Summary
Lay description: Collectively, diseases of the vascular system contribute immensely to the burden of health care in Australia. Notably, abnormal blood vessel formation and function (angiogenesis) has been identified as a major cause or contributor to the vascular complications associated with inflammation, cancer, rheumatoid arthritis and diabetes. Endothelial cells are one of the principle cells of blood vessels forming a barrier between the blood and tissues. This project aims to understand th ....Lay description: Collectively, diseases of the vascular system contribute immensely to the burden of health care in Australia. Notably, abnormal blood vessel formation and function (angiogenesis) has been identified as a major cause or contributor to the vascular complications associated with inflammation, cancer, rheumatoid arthritis and diabetes. Endothelial cells are one of the principle cells of blood vessels forming a barrier between the blood and tissues. This project aims to understand the process whereby mature endothelial cells are formed and how replacement of damaged endothelial cells is normally achieved. Stem cell therapy is considered the new frontier for the treatment of many diseases. Understanding how endothelial progenitor cells differentiate to mature endothelial cells and the signals which operate inside the cell may allow therapeutic manipulation of key target moecules in order to limit or control inflammation, tumourigenesis, rheumatoid arthritis and diabetic retinopathy. Our results suggest that one target maybe the enzyme sphingosine kinase.Read moreRead less
Lymphoid Organ Development: Synthetic Organogenesis Of Artificial Spleen And Characterisation Of Tissue-specific Hematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$350,232.00
Summary
Spleen is an organ which filters blood circulating around the body and provides immune protection against blood-borne pathogens. Research into spleen development will attempt to synthesise artificial spleen tissue, leading to possible tissue replacement therapies or enhancement of immunity towards infection or cancer. Cellular development in spleen will also be investigated with a view to identifying novel white blood cell subsets that have potential for becoming new targets for immunotherapy.
Regulation Of T Cell Effector Function In Peripheral Tissues
Funder
National Health and Medical Research Council
Funding Amount
$698,550.00
Summary
Protection from infections relies on different types of immune cells. While some of these cells are found in the blood, others reside in peripheral tissues such as the skin. We will analyse the function of these peripheral immune cells to understand how they work to fight off infections. We will also investigate how so-called memory cells that permanently reside in peripheral tissues can protect from re-infection with similar bacteria or viruses.