Characterisation Of SRY Macromolecular Complexes To Provide An Enhanced Understanding Of Human Genetic Sex Reversal And Embryonic Sex Determination
Funder
National Health and Medical Research Council
Funding Amount
$237,360.00
Summary
SRY is the most important gene in the determination of human sex. Mutations in the SRY gene that disrupt its ability to interact with other cellular proteins that regulate its function have shown to result in genetic sex reversal. This project will provide a detailed structural profile of the interfaces that are critical for sex determination, provide a molecular basis for XY-genetic sex reversal, and an enhanced understanding of foetal development.
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.
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
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.
De-differentiation Of Committed Cells Into Haematopoietic Stem Cells By The Instructive Role Of The Transcription Factor HOXB4
Funder
National Health and Medical Research Council
Funding Amount
$683,040.00
Summary
Blood stem cells are long-lived and can give rise to every cell type of the blood system and due to these properties they are currently used in the clinics. Despite their importance, our knowledge of the mechanisms the control the multiplication of these rare cells is very scarce. This proposal aims to identify key factors that have the potential to convert mature, easy available blood cells into stem cells. This knowledge has to potential to lead to novel system that allow the expansion of stem ....Blood stem cells are long-lived and can give rise to every cell type of the blood system and due to these properties they are currently used in the clinics. Despite their importance, our knowledge of the mechanisms the control the multiplication of these rare cells is very scarce. This proposal aims to identify key factors that have the potential to convert mature, easy available blood cells into stem cells. This knowledge has to potential to lead to novel system that allow the expansion of stem cells for transplantations in the future.Read moreRead less
Cellular And Molecular Characterization Of Erythroid Enucleation
Funder
National Health and Medical Research Council
Funding Amount
$671,950.00
Summary
A major challenge for transfusion medicine is the constant difficulties in obtaining enough supply of specific red blood cell (RBC) subtypes. In this proposal, we will identify the key steps of enucleation (extrusion of nucleus), a rate limiting process for the in vitro production of RBCs. A better understanding of this process will lead to improved strategies for the efficient and rapid production of self-generated RBCs for individual patient transfusion.
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.
Dissecting The Molecular Mechanisms During Reprogramming Of Different Somatic Cells Into Induced Pluripotent Stem Cells And The Plasticity Potential Of Their Intermediate Stages.
Funder
National Health and Medical Research Council
Funding Amount
$234,965.00
Summary
I am a biochemist interested in the molecular mechanisms involved in gene expression and how these processes govern cell identity. I use a combination of mouse models, biochemical techniques and bioinformatics to study the _reprogramming� of adult cells into embryonic stem-like cells and how this technology can be used to generate different cell types for use in cellular replacement therapies and drug screening.
cell-cell adhesive force in vascular development. This project aims to utilize groundbreaking new approaches to visualize cell-cell adhesive forces in vascular development. Vascular system development is one of the earliest events in the vertebrate embryo. It has long been established that one major contributor to the formation of new vessels is physical force, which can be generated through blood flow or cell-cell interactions during tissue morphogenesis. The project plan utilizes live imaging ....cell-cell adhesive force in vascular development. This project aims to utilize groundbreaking new approaches to visualize cell-cell adhesive forces in vascular development. Vascular system development is one of the earliest events in the vertebrate embryo. It has long been established that one major contributor to the formation of new vessels is physical force, which can be generated through blood flow or cell-cell interactions during tissue morphogenesis. The project plan utilizes live imaging in zebrafish and a new generation of biosensors to gain a vastly deeper understanding of how force controls vessel formation.Read moreRead less
Studying early human kidney development using stem cells. This project aims to improve our understanding of cell types, lineage relationships, cell-cell interactions and morphogenetic processes in human kidney development. Investigators have developed a method to produce multicellular kidney organoids from human pluripotent stem cells (hPSC). This project will use gene-edited reporter hPSC lines and high-res imaging to study the lineage relationships and morphogenetic mechanisms of these human k ....Studying early human kidney development using stem cells. This project aims to improve our understanding of cell types, lineage relationships, cell-cell interactions and morphogenetic processes in human kidney development. Investigators have developed a method to produce multicellular kidney organoids from human pluripotent stem cells (hPSC). This project will use gene-edited reporter hPSC lines and high-res imaging to study the lineage relationships and morphogenetic mechanisms of these human kidney organoids. This project aims to validate the origin of nephrons in kidney organoids, study the origin of the renal stroma versus the nephron progenitor, and monitor nephron patterning and segmentation at a clonal level. This will improve our knowledge of human kidney development in a human model.Read moreRead less