Making Human T- And B-lymphocytes For Immunotherapy And Antibody Production
Funder
National Health and Medical Research Council
Funding Amount
$795,880.00
Summary
Lymphocytes are white blood cells that are involved in producing antibodies, killing defective cells, or killing cells infected with viruses. In recent years, researchers have found ways to harness lymphocytes to develop medicines for treating a variety of different cancers. In this project, we will establish methods to make human lymphocytes in the laboratory from stem cells, paving the way for the broader application of this cell type to new therapies.
Deciphering The Epigenetic Code Of T Lymphocyte Stability In Disease
Funder
National Health and Medical Research Council
Funding Amount
$662,785.00
Summary
T lymphocytes defend against invading pathogens and establish immunological memory to protect us if the infection returns. As there are many different types of pathogens, T lymphocytes must be flexible in the way they respond to infection but also stable once they have decided on the appropriate type of response. This complex decision-making appears to be dictated by epigenetic changes to the chromatin state of the cell. This work will uncover epigenetic factors that maintain this balance to pro ....T lymphocytes defend against invading pathogens and establish immunological memory to protect us if the infection returns. As there are many different types of pathogens, T lymphocytes must be flexible in the way they respond to infection but also stable once they have decided on the appropriate type of response. This complex decision-making appears to be dictated by epigenetic changes to the chromatin state of the cell. This work will uncover epigenetic factors that maintain this balance to protect us against disease.Read moreRead less
SULT4A1 is not a sulfotransferase, but a sulfotransferase inhibitor. It forms high affinity heterodimers with other sulfotransferases via a conserved dimerisation site in its carboxyl terminus attenuating catalytic activity. Consequently, it is important for the metabolism of numerous important molecules including estrogens, thyroid hormones, neurotransmitters and many therapeutic agents.
Epigenetic Regulation Of Cell Lineage Differentiation In The Early Embryo
Funder
National Health and Medical Research Council
Funding Amount
$440,983.00
Summary
Exposure of embryos to a range of stresses can increase the predisposition to chronic diseases of adulthood. Stressing embryos at critical stages of development cause errors in reorganization of the nucleus that are required for normal gene expression. These errors are propagated into adulthood. This project will map the normal processes of nuclear reorganization and define how stress to the embryo changes this process, allowing an understanding of the causes of some important chronic diseases.
IL21, B-cell Proliferation And The Mechanism Of Memory Formation
Funder
National Health and Medical Research Council
Funding Amount
$981,896.00
Summary
Our immune system can ‘remember’ old infections, which is why we do not suffer from the same pathogen multiple times and why vaccines work. Much of this protection is due to memory B-cells, of which there are different kinds. We think the different memory B-cell subsets have different functions and understanding how they are made and how this is controlled will help us improve responses to critical infections – HIV, Flu – and in critical patient groups – aged people and transplant recipients.
Overcoming The Differentiation Block In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$811,669.00
Summary
Acute myeloid leukaemia (AML) is an aggressive leukaemia with poor overall survival. About 50% of AML cases have genetic mutations that disable PU.1, which in turn alters the expression of many other genes that cause leukaemia. We have developed new AML models allowing reversible inhibition of PU.1, and have shown that re-engaging PU.1 function causes AML regression. This project aims to understand PU.1 functions in AML and identify rational drug targets for treatment-resistant disease.
Dissecting Apoptosis And IL-15 Dependent Homeostasis Pathways Of Natural Killer (NK) Cells
Funder
National Health and Medical Research Council
Funding Amount
$423,809.00
Summary
We will investigate how the cytokine IL-15 regulates the homeostasis of natural killer (NK) cells. NK cells are critical for immune responses against invading viruses or bacteria or upon detection of transformed cells. NK cells are primed to attack infected or transformed cells and are rapidly activated by direct interaction or by soluble signals. Knowledge of how NK cells development and how their numbers and function are controlled is paramount to understanding infectious disease immunology an ....We will investigate how the cytokine IL-15 regulates the homeostasis of natural killer (NK) cells. NK cells are critical for immune responses against invading viruses or bacteria or upon detection of transformed cells. NK cells are primed to attack infected or transformed cells and are rapidly activated by direct interaction or by soluble signals. Knowledge of how NK cells development and how their numbers and function are controlled is paramount to understanding infectious disease immunology and developing better immuno-therapies.Read moreRead less
Identification Of Haematopoietic Stem And Progenitor Cell Subpopulations
Funder
National Health and Medical Research Council
Funding Amount
$873,525.00
Summary
We want to dissect the machinery underlying how each and every individual stem and progenitor cell generates the different blood cell types. We have at our disposal the latest molecular and computational technologies to do this. Knowledge gained from this project could be used for tissue engineering to make blood cells on demand for patients with immune deficiency, or alternatively to treat leukaemia patients where blood cells are overproduced.
Computational Reconstruction And Validation Of A Gene Regulatory Network Controlling Differentiation Of B Cells To Antibody-secreting Plasma Cells
Funder
National Health and Medical Research Council
Funding Amount
$618,152.00
Summary
Regulation of B cell differentiation, which occurs when our body responds to antigen infection is tightly controlled by a gene regulatory network. This project will be the first study to reconstruct a regulatory network for this process by using genome-wide expression and transcription factor binding data. The research finding from this study will elucidate the molecular mechanisms regulating this process and will shed new light on how this network is altered in lymphoma and myeloma.
ARC, A Newly Identified Regulator Of Chondrocyte Differentiation And Death, Is A Novel Therapeutic Target For OA
Funder
National Health and Medical Research Council
Funding Amount
$763,983.00
Summary
We have identified a critical regulator of the survival and normal metabolism of the cells in articular cartilage. Loss of this molecule is an early event in joint injury that leads to osteoarthritis (OA). The current proposal will determine the mechanisms whereby this protein functions to protect cartilage breakdown in OA, how its levels in chondrocytes are regulated in both healthy and diseased conditions, and at what stages of disease increasing its expression protects against OA progression.