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Molecular Dissection Of Cytokine-mediated Regulation Of Human B-cell Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$119,314.00
Summary
Interleukin 21 is a molecule which activates B cells. Defects in this pathway cause immunodeficiency where individuals cannot make antibodies, while constant activation has been reported in mouse models of autoimmunity. Examining these pathways will shed light on the causes of human immune disease, and may reveal molecules that could be targeted for the treatment of immunodeficiency and autoimmunity. Amplification of normal immune responses could lead to the development of improved vaccines.
Lymphocyte Differentiation And Genetics Of Primary Immunodeficiency
Funder
National Health and Medical Research Council
Funding Amount
$143,676.00
Summary
Primary immunodeficiency diseases affect a large number of individuals. Due to abnormal immune responses, these people are at risk of frequent, severe infections, as well as complications of autoimmune disease and cancer. Treatment often involves regular immunoglobulin (antibody) replacement. Through a better understanding of the mechanisms underlying these immunodeficiency diseases, we hope to be able to determine genetic causes, and more cost-effective and targeted treatment options.
Exploiting And Defining The Immune Regulatory Activities Of BET Bromodomain Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Immune-based agents such as “checkpoint inhibitors” have the ability to re-awaken our own immune systems and activate previously dormant anti-tumour responses. We have discovered that small molecule inhibitors of gene regulatory proteins called bromodomain proteins act synergistically with checkpoint inhibitors in mouse cancer models. I will define the molecular and biological events underpinning this novel combination approach and assess the effects of the combination across different tumours.
Pro-apoptotic Therapies For The Treatment Of Mycobacterium Tuberculosis Disease And Latent Infection
Funder
National Health and Medical Research Council
Funding Amount
$140,949.00
Summary
Programmed cell death has an important role in our ability to fight organisms. Upon infection, processes result in activation of death-inducing cascades, resulting in death of cell and pathogen. M. tuberculosis, an escalating health problem, has developed mechanisms to prevent this, leading to latency. This study, which uses mouse M.tb models, hypothesises that reversal of these mechanisms, using drugs currently in trial in leukaemia (ABT-737 & BV6), may lead to clearance of infection.
Regulation Of Extrinsic Death Pathways In Neutrophils
Funder
National Health and Medical Research Council
Funding Amount
$84,656.00
Summary
During infection, the lifespan of neutrophils normally increases despite an abundance of neutrophil death signals in inflamed tissues. Altered lifespan of neutrophils has been reported in diseases associated with influenza, Streptococcus, RSV and cytomegalovirus infection. Our research has discovered a relationship between the two dominant death pathways in neutrophils, indicating that alterations in one death pathway protect the neutrophil from death signals from the second death pathway.
Cell Survival Pathways As Potential Targets In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$142,914.00
Summary
Cancer cells are characterised by their capacity for relentless growth, survival and evasion of cell death. This proposal will use patient derived xenograft models of primary breast cancer to test the hypothesis that addition of BH3-mimetics could improve response to anti-HER2 therapy. This technique involves transplantation of patient tumours into immune-compromised mice. This represents a useful method for testing new agents.
Transcriptional Control Of Peripheral T Cell Differentiation During Pathogen Infection And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$92,314.00
Summary
White blood cells, specifically helper and killer T cells, play an important role in fighting infection. They are tightly regulated and if not properly controlled can lead to aggressive autoimmune diseases such as diabetes and multiple sclerosis. My studies will elucidate the mechanisms behind the regulation of T cells at steady-state and during disease. Insights gained from this project will have implications for the design of new approaches to combat infectious and autoimmune diseases.
Examining The Specific Vulnerability Of Dopaminergic Cells To Bioenergetic Defects Using Patient-derived Induced Pluripotent Stem Cells As A Model Of Parkinson’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$112,366.00
Summary
The project will develop new cell models of Parkinson's disease utilising the recently discovered technique of inducing pluripotent stem cells from adult skin cells and differentiating them into the type of neurons that are affected in Parkinson's disease. The novel method will allow further insights to be gained into the molecular pathways involved in the disease and facilitate a search for means to rescue these cells from neurodegenerative processes.
Growth factors are essential molecules for normal brain development. Variations in the amount of the different growth factors have been implicated in such diseases as AlzheimerÍs and ParkinsonÍs disease. This project will study the precursor of a growth factor known as brain derived neurotrophic factor (BDNF) and what specific roles the precursor might play in brain development.
Improving Health Services Around The Time Of Childbirth In Places Where Death Rates Are High And Home-births Common
Funder
National Health and Medical Research Council
Funding Amount
$119,335.00
Summary
In settings close to Australia where death rates among mothers and newborns remain high, it is common for childbirth to take place outside of health facilities. This research will develop feasible options for countries aiming to simultaneously improve care in first-line health facilities (which often takes some years), and simultaneously provide some limited services in the home that can reduce deaths immediately.