Defining The Role Of VEGF And Vascular Formation In Craniofacial Development
Funder
National Health and Medical Research Council
Funding Amount
$636,417.00
Summary
Aberrant neural crest cell development gives rise to common congenital malformations such as cleft lip and/or palate and cardiac outflow tract defects that effect over 1% of all births. As the aetiology of these disorders are largely unknown it is critical to understand the cell and molecular mechanisms coordinating NCC development such that alternative therapies may be devised to target the underlying pathological defects and to provide definitive diagnostic / prognostic tools.
Understanding how the brain grows and is organised is one of the great challenges of science. This project seeks to identify key regulators of neural progenitors as these are the building blocks from which all brains cells are derived. This knowledge may also identify new avenues through which to manipulate neural progenitor function. This has implications not only for normal brain development but also potential therapies for neural disorders and disease.
Stem cell to differentiation occurs in a bi-directional fashion. Dedifferentiation which allows specialized cells to become stem cells has been found to be important in both cancer and regeneration. In this proposal, we will investigate the metabolic reprogramming of neuronal dedifferentiation. The findings from this study will better inform us on how to specifically target tumours that arise from dedifferentiation.
Defining The Role Of Nedd4 In Neural Crest Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$541,565.00
Summary
Neural crest cells are specialised stem cells that give rise to many tissues and organs during embryonic development. We recently identified an essential role for a regulatory protein in neural crest cells. Our research is aimed at understanding how this protein influences the growth of structures such as the heart and facial skeleton. Understanding these processes underpins the ultimate goal of implementing diagnostic and preventative medicine for highly prevalent congenital birth defects.
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.
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
Determining The Role Of Rel/NF-kB Transcription Factors In Myeloid Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$500,944.00
Summary
Different types of mature blood cells arise from stem cells in a process involving changes in gene expression that dictate which types of blood cells ultimately develop. A family of gene regulatory proteins called NF-kB transcription factors has been found to control the pattern of gene expression in a particular blood cell precursor called a granulocyte macrophage precursor (GMP) that normally generates two types of mature blood cells called macrophages and neutrophils. In the absence of NF-kB ....Different types of mature blood cells arise from stem cells in a process involving changes in gene expression that dictate which types of blood cells ultimately develop. A family of gene regulatory proteins called NF-kB transcription factors has been found to control the pattern of gene expression in a particular blood cell precursor called a granulocyte macrophage precursor (GMP) that normally generates two types of mature blood cells called macrophages and neutrophils. In the absence of NF-kB proteins, a change in the pattern of gene expression in GMPs leads to an imbalance in production of these two blood cell types that now favours the generation of neutrophils. This work will provide insight into the molecular mechanisms of blood cell development regulated by NF-kB. With disturbances in the balance of blood cell formation representing a hallmark of leukemia, understanding how this process is normally controlled may have important implications for developing therapeutic strategies to combat various types of leukemias.Read moreRead less