DECIPHERING THE ROLE OF FOXP1 IN MAMMARY STEM CELLS AND DEVELOPMENT
Funder
National Health and Medical Research Council
Funding Amount
$569,109.00
Summary
Breast (mammary) epithelial cells undergo major changes across developmental stages, including puberty, pregnancy and lactation. This project will focus on the role of the molecular regulator, Foxp1, and how it influences normal mammary maturation. This work will inform whether Foxp1 is critical for controlling the activation of dormant stem cells and if this pathway can contribute to breast cancer formation when disrupted.
Understanding How Defects In Chromosome Structure Can Cause Disease
Funder
National Health and Medical Research Council
Funding Amount
$546,557.00
Summary
The correct folding of DNA is critical to a cell's survival. This is orchestrated by a special class of proteins called the condensins. Defects in condensin lead to aberrant chromosome folding and disease. We aim to understand how condensin folds chromosomes and why mutations in condensin are increasingly associated with disease.
A Stem Cell-specific MicroRNA-independent Function Of Drosha
Funder
National Health and Medical Research Council
Funding Amount
$637,702.00
Summary
Stem cells are responsible for producing and replenishing the ~200 specialised cell types in our body. Our goal is to understand the molecular switches that control the function of these cells. We recently discovered that the activity of certain genes within stem cells is controlled by degradation. This degradation is absolutely crucial for safeguarding the function of stem cells. This project will investigate how this novel mechanism is controlled within these cells.
Elucidating The Cellular Processes That Are Critical For P53 Mediated Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$1,016,108.00
Summary
p53 is a tumour suppressor gene that is mutated in ~50% of human cancers. Mutations in p53 cause development of cancer and render malignant cells resistant to chemotherapy. We have identified genes regulated by p53 that appear critical for its tumour suppressive function. In this project, we will use innovative novel genetic tools to discover the cellular and biochemical functions of these genes. The ultimate goal of our studies is to identify novel targets for anti-cancer therapy.
The C-type Lectin Mincle Exemplifies A New Mode Of Sterile Inflammation In Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$609,237.00
Summary
This project investigates two of the life-changing cardiovascular events that most commonly impact on Australians today; Heart attack and Stroke. These diseases often leave individuals debilitated with a long recovery period, and for many people the event is fatal. We have shown that blocking the action of an immune component, "Mincle", reduces the inflammation associated with stroke, and improves recovery. This project looks at what Mincle does in brain and heart muscle, and why blocking Mincle ....This project investigates two of the life-changing cardiovascular events that most commonly impact on Australians today; Heart attack and Stroke. These diseases often leave individuals debilitated with a long recovery period, and for many people the event is fatal. We have shown that blocking the action of an immune component, "Mincle", reduces the inflammation associated with stroke, and improves recovery. This project looks at what Mincle does in brain and heart muscle, and why blocking Mincle protects cells from loss of oxygen.Read moreRead less
Regulation Of TNF Expression In Inflammation And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$728,447.00
Summary
By studying a spontaneous mutation in mice, we have found an error in the TNF gene (a major factor in many inflammatory diseases) that causes severe arthritis, heart valve disease and gut inflammation. We have also identified new regulators of TNF expression, which might be useful therapeutic targets to limit inflammation. We intend to study the role of these regulators in controlling the expression of TNF, and the link between chronic inflammation and the development of cancer.
Cancers arise as a result of the impairment of critical cellular processes following the mutation of important regulatory genes. I am a molecular biologist and I study how the proteins of the Bcl-2 family regulate apoptosis, a process of cell death essential to maintain homeostasis in multicellular organisms, with the aim of designing drugs to kill cancer cells selectively. I am also interested in discovering new genes involved in the development of cancer using new genomics technology.
The Mechanism Of Cell Death In Response To Cytoplasmic DNA, And Its Role In Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$517,897.00
Summary
DNA in mammalian cells is in a structure known as the nucleus. Retroviruses such as HIV generate DNA outside the nucleus in the cytoplasm, and detection of DNA in the cytoplasm can lead to cell death, as a defence. All cells carry the remnants of ancient retroviruses in their nuclear DNA. These are normally inactive but may contribute to cancer when activated. This project investigates how normal cells die with cytoplasmic DNA, and whether a defect in this process promotes development of cancer.
Alternative Splicing- A Regulatory Mechanism Determining Self-renewal And Pluripotency Of ES And IPS Cells
Funder
National Health and Medical Research Council
Funding Amount
$664,650.00
Summary
Stem cells hold great promise in cell replacement therapies and may provide models to study human diseases and to screen new pharmaceuticals. For successful future therapeutic applications, a deeper understanding of the molecular mechanisms governing the behavior of stem cells is crucial. In this proposal we will investigate the role of alternative splicing in the control of the fundamental properties of stem cells, and identify target RNAs and gene expression networks regulated by splicing fact ....Stem cells hold great promise in cell replacement therapies and may provide models to study human diseases and to screen new pharmaceuticals. For successful future therapeutic applications, a deeper understanding of the molecular mechanisms governing the behavior of stem cells is crucial. In this proposal we will investigate the role of alternative splicing in the control of the fundamental properties of stem cells, and identify target RNAs and gene expression networks regulated by splicing factors.Read moreRead less
Blimp-1: A Master Regulator Of B-lymphocyte Terminal Differentiation?
Funder
National Health and Medical Research Council
Funding Amount
$154,250.00
Summary
B lymphocytes are the antibody-producing cells of the immune system. They are formed in the bone marrow, and are exported to the body to circulate, searching for signs of infection. These circulating cells are not fully mature, but when they encounter an invader, with the help of other immune cells, they change. Most become antibody-producing cells, the final, operational cells of the B cell lineage. A few cells are set aside as memory cells that can rapidly become antibody-producing cells shoul ....B lymphocytes are the antibody-producing cells of the immune system. They are formed in the bone marrow, and are exported to the body to circulate, searching for signs of infection. These circulating cells are not fully mature, but when they encounter an invader, with the help of other immune cells, they change. Most become antibody-producing cells, the final, operational cells of the B cell lineage. A few cells are set aside as memory cells that can rapidly become antibody-producing cells should the same infection occur again. This is the basis of vaccination. The secretion of antibodies into the serum (that can bind to and eliminate an invader anywhere in the body) is the main function of B lymphocytes. This project will study the genes that allow B cells to become antibody-secreting cells (called ASC). We will focus on the gene for Blimp-1, the B lymphocyte-induced maturation protein, which has been called the master regulator of ASC formation. This claim is based largely on circumstantial evidence, and has not been directly tested genetically. We have made a mouse in which the Blimp-1 gene has been altered so that we can disable it in carefully controlled way. Using this knockout mouse, we can directly test the requirement for Blimp-1 in ASC and in other cell types. We will study these animals, using many tests that can accurately measure the behaviour of isolated cells, or the immune responses of the animals. We will examine other genes that are thought to be required for ASC to form or to perform their work, to see if loss of Blimp-1 (a known gene silencer) has impacted on these other genes. In this way, we expect to identify the genetic program that drives a B cell to become a mature ASC. Using this knowledge, we hope eventually to be able to study diseases of ASC in humans (as occur in allergy, asthma, rheumatoid arthritis and leukaemia). This information may also be used to improve the outcome of vaccination.Read moreRead less