Determining The Role Of Rel/NF-kB Transcription Factors In CD8 T Cell Homeostasis.
Funder
National Health and Medical Research Council
Funding Amount
$426,500.00
Summary
NF-kB proteins comprise a family of transcription factors that regulate key genes involved in immune responses, inflammation, cell death and proliferation. This family of proteins are potential drug targets for treatment of various diseases. How and when such inhibitors are used in clinical situations depends on understanding how and which cells of the immune system are specifically affected by the absence of NF-kB proteins. In a number of treatment settings intercurrent viral infections occur f ....NF-kB proteins comprise a family of transcription factors that regulate key genes involved in immune responses, inflammation, cell death and proliferation. This family of proteins are potential drug targets for treatment of various diseases. How and when such inhibitors are used in clinical situations depends on understanding how and which cells of the immune system are specifically affected by the absence of NF-kB proteins. In a number of treatment settings intercurrent viral infections occur frequently and therefore there is an even greater need to understand how the immune system may be affected or compromised in response to the primary treatment. This work will provide insights into the cellular and molecular mechanisms affected by the absnece of a particular NF-kB family member (NF-kB1) in CD8 T cells during normal T cell homeostasis and when challenged with viruses. What we learn from our experiments could have important implications for the development of vaccines.Read moreRead less
Roles Of Signalling In The Control Of Immune System Development, Function And Pathology
Funder
National Health and Medical Research Council
Funding Amount
$737,936.00
Summary
This research focuses on the function of the NF-?B and MAP kinase biochemical pathways in immune cells. Both pathways regulate gene expression controlling the development, division, viability and function of immune cells. Consistent with these roles, impaired regulation of these pathways contributes to many immune related diseases. My goal is to utilize information learnt about these pathways and apply it to developing therapies for treating diseases afflicting the immune system.
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
NFkB1 Is A Novel Regulator Of CD8+ T Cell Development And Memory Cell Generation
Funder
National Health and Medical Research Council
Funding Amount
$438,039.00
Summary
This project is focused on understanding the role of a regulatory protein- NFkB1 and how it is capable of controlling the development of a class of white blood cells termed T cells. Using a mouse model, we reveal how the absence of NFkB1 is important for producing memory T cells. Studies are proposed to determine whether this is an novel way for generating long lived memory T cells against viral infections and cancer, and potentially a new strategy for vaccine development.
Molecular And Functional Charcterization Of A Novel Population Of Foxp3+ Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$394,274.00
Summary
Regulatory T cells (Tregs) are essential for the prevention of autoimmunity and death. We have identified a new population of effector or ïactiveÍ Tregs, and identified some of the proteins that are required for these cells to function. We now aim to examine the development of these cells in detail, illuminate their precise function, their distribution and mode of action. This has potentially huge implications in treatment and diagnosis of autoimmunity, cancer or transplantation.
Protective memory T cell immune responses defend our body against pathogens by the rapid induction of killer T cells. This protects us from severe or perhaps even fatal disease. Our work will provide insights to how the body makes these potent ‘footsoldiers’. This work will have important implications for identifying how these immune cells can be manipulated to prevent and treat pathogenic and autoimmune disease and for optimising approaches to vaccination.
Investigating B Cell Development, Maintenance And High-affinity Antibody Production By ENU Mutagenesis
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
B cells are essential for the protection against infections. This application aims to identify new genes that are crucial for the development or function of B cells and will investigate how mutations in newly discovered genes contribute to defects in the development and function of B cells and the pathogenesis of B cell leukaemia.
Roles Of ID2 In Regulating Critical Innate And Adaptive Arms Of The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$597,418.00
Summary
The immune system protects us from a wide range of pathogens and foreign invaders. Natural killer (NK) cells and T cells are an critical component of the immune system due to their ability to detect and kill virally infected and malignant cells. Our work will endeavor to understand the molecular steps essential for these cells to develop and become armed to ensure immune protection.