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
Transcriptional Regulation Of Specialized Subsets Of Dendritic Cells In Control Of Infection
Funder
National Health and Medical Research Council
Funding Amount
$616,912.00
Summary
Immune protection against viruses and bacteria depends on specialized cells called dendritic cells that display components of the invading organisms on their surface. There are multiple different types of dendritic cell and each population plays a specialized role in defending the body against infection. Our work will provide the framework for directly targeting these cells for novel vaccines to re-program the immune system for clinical conditions such as cancer, allergy and autoimmunity.
Follicular Helper T Cell Development And Function: From Mechanisms To Application
Funder
National Health and Medical Research Council
Funding Amount
$401,361.00
Summary
Antibodies are the basis of most successful vaccinations. Diminished antibody responses lead to immunodeficiency while excessive antibody responses contribute to autoimmune diseases. We are studying a newly identified specialised helper T cell subset, termed follicular helper T cells, which is essential to regulate the high-affinity and long-lived antibody responses. The knowledge should provide new strategies to design better vaccines, to control infections, or to treat autoimmune disorders.
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
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.
The NF-kB Transcription Factors C-Rel And RelA Control Multiple Steps In Natural CD4 Regulatory T Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$566,592.00
Summary
An unfortunate consequence of immune function is that occasionally rogue immune cells are produced that attack the host and lead to the development of so-called autoimmune diseases such as arthritis. Normally a white blood cell called a regulatory T cell suppresses these self-reactive immune cells. We have identified factors that govern the generation of regulatory T cells. Understanding how these factors work should permit the development of new strategies to combat autoimmune diseases. ?
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.