Differential roles of gene family members in development of a cell lineage. This project aims to investigate how a family of genes influence cells in the testis to become mature sperm. Testicular cells regulate gene activity via the Snail family of proteins during sperm development, and interruption of their activities reduces fertility in mice and fruit flies. The project aims to use genetic, cell biological and biochemical studies in Drosophila and mice to compare different Snail family protei ....Differential roles of gene family members in development of a cell lineage. This project aims to investigate how a family of genes influence cells in the testis to become mature sperm. Testicular cells regulate gene activity via the Snail family of proteins during sperm development, and interruption of their activities reduces fertility in mice and fruit flies. The project aims to use genetic, cell biological and biochemical studies in Drosophila and mice to compare different Snail family proteins in spermatogenesis. The outcomes will define the different roles of highly similar proteins from the same family in differentiation of a single cell lineage. This is important in generating functional tissues using in vitro laboratory approaches or understanding how normal development and developmental disorders arise.Read moreRead less
Characterisation Of Notch Asparaginyl Hydroxylation By FIH-1.
Funder
National Health and Medical Research Council
Funding Amount
$307,841.00
Summary
Cells within our body receive numerous signals telling them when to grow, when to turn into another cell type and exactly what type, and even how to respond to situations like low oxygen. These signals and cells response are very important during embryonic development, when these signals cause a single cell to become a complete person, and also in adults. Here in the embryo, and also in adults, stem cells are very important because they can become many different kinds of cells, depending on what ....Cells within our body receive numerous signals telling them when to grow, when to turn into another cell type and exactly what type, and even how to respond to situations like low oxygen. These signals and cells response are very important during embryonic development, when these signals cause a single cell to become a complete person, and also in adults. Here in the embryo, and also in adults, stem cells are very important because they can become many different kinds of cells, depending on what the body needs. When the signals don't work properly, they cause major problems and diseases, from birth defects, to cancer. Notch is an important protein involved in receiving and passing on certain signals, and is found in organisms as diverse as worms and humans. It tells cells, especially stem cells and other similar cells, when and how to change from one type of cell to another. For example, it is very important in the generation of many different types of blood cells from a single precursor cell. Notch has also been implicated in human diseases such as cancer, where signalling goes wrong and cells keep multiplying out of control, and also certain types of heart disease. Another protein, called FIH, is an oxygen sensor that signals to the cell when there is not enough oxygen around. FIH has also been implicated in cancer and heart disease. We have recently found evidence suggesting that FIH can also influence the activity of the Notch proteins. This means that oxygen levels can potentially have an effect on stem cells and other processes controlled by Notch, and may be very important in cancer and other diseases. This project will first confirm the connection between FIH and Notch. There are a number of different Notch proteins, so we will see if this connection works with all of them. It will also try and work out the consequence of this connection is and how important it is. Finally, the likely biological consequences on human diseases, specifically cancer.Read moreRead less
Understanding the potency and role of individual stem cells in the skin using Rainbow technology. To renew itself, the skin and its components rely on the activity of stem cells. This project will define more precisely the role of each individual stem cell by labelling them with a unique colour and following its fate. This project has the potential to change our current view on how the skin maintains and repairs itself.
The lipidomics of cell fate. This project aims to dissect the roles of lipids in cell fate. The study of lipids, or lipidomics, is an emerging and exciting area of biological science. The fundamental roles of lipids in development remain vastly understudied. This project will look at reprogramming of somatic cells into stem cells, their pluripotency and differentiation. This will be complemented with studies in the zebrafish, which permits the direct study of cell fate in vivo. This approach is ....The lipidomics of cell fate. This project aims to dissect the roles of lipids in cell fate. The study of lipids, or lipidomics, is an emerging and exciting area of biological science. The fundamental roles of lipids in development remain vastly understudied. This project will look at reprogramming of somatic cells into stem cells, their pluripotency and differentiation. This will be complemented with studies in the zebrafish, which permits the direct study of cell fate in vivo. This approach is a powerful way to unlock major events involved in development and to unmask the roles of lipids in these fundamental mechanisms.Read moreRead less
Mechanism and function of dying cell disassembly. This project aims to elucidate the molecular machinery that disassembles dying cells, and the role of this process in cell clearance. Billions of cells in the body die daily as part of normal turnover. Dying cells must be rapidly removed, as their accumulation can interfere with normal tissue functions. To efficiently clear dead cells, dying cells can disassemble into smaller fragments that neighbouring cells engulf. Understanding the mechanistic ....Mechanism and function of dying cell disassembly. This project aims to elucidate the molecular machinery that disassembles dying cells, and the role of this process in cell clearance. Billions of cells in the body die daily as part of normal turnover. Dying cells must be rapidly removed, as their accumulation can interfere with normal tissue functions. To efficiently clear dead cells, dying cells can disassemble into smaller fragments that neighbouring cells engulf. Understanding the mechanistic basis and function of dying cell disassembly is expected to generate knowledge of the downstream consequence of cell death. This breakthrough will be important in many fields of research including cell biology and biochemistry, and generate basic knowledge that can ultimately be applied in medical science to understand or treat pathological conditions associated with cell death.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140100500
Funder
Australian Research Council
Funding Amount
$383,066.00
Summary
Unravelling the holistic genetic control of vertebrate development. Understanding the genetic regulation of embryo formation is the cornerstone of developmental biology. As four per cent of Australian children are born with some form of prenatal defect, understanding the basic biology of embryogenesis is paramount for long-range development of future therapies. We have identified a highly conserved transcription factor, Grhl3, which regulates multiple stages of embryonic formation. Using advance ....Unravelling the holistic genetic control of vertebrate development. Understanding the genetic regulation of embryo formation is the cornerstone of developmental biology. As four per cent of Australian children are born with some form of prenatal defect, understanding the basic biology of embryogenesis is paramount for long-range development of future therapies. We have identified a highly conserved transcription factor, Grhl3, which regulates multiple stages of embryonic formation. Using advanced genetic models, this project will characterise the role of Grhl3 in the regulation of cellular migration and craniofacial skeleton and brain development. The project will also identify the target genes which Grhl3 regulates. The identification of such transcriptional networks is imperative to understanding the holistic molecular control of embryogenesis.Read moreRead less
Microenvironments which support extramedullary hematopoiesis. Tissue regeneration is a breakthrough technology absolutely dependent on knowledge of the stem cells and stromal cells which support differentiation and tissue development. This project investigates the stromal cell types in spleen which can regenerate blood-forming cells in an ectopic tissue site or artificial matrix.
Role of senataxin protein in meiotic recombination and sex chromosome inactivation. Senataxin is a protein defective in the human genetic disorder ataxia oculomotor apraxia type 2. This project is designed to carry out mechanistic studies on the protein to establish its normal role in the cell.
Using viral inhibitors to understand the regualtion of apoptosis. Apoptosis is a form of cell death that is critical for the development and well-being of multicellular organisms. The activity of Bak or Bax, two members of the Bcl-2 family, are essential for apoptosis to proceed, but how the activity of these two proteins is regulated is unclear. Many viruses encode inhibitors of apoptosis and the project will make use of two novel viral inhibitors that specifically target Bak. The project aims ....Using viral inhibitors to understand the regualtion of apoptosis. Apoptosis is a form of cell death that is critical for the development and well-being of multicellular organisms. The activity of Bak or Bax, two members of the Bcl-2 family, are essential for apoptosis to proceed, but how the activity of these two proteins is regulated is unclear. Many viruses encode inhibitors of apoptosis and the project will make use of two novel viral inhibitors that specifically target Bak. The project aims to determine how the Bak inhibitors function and to provide valuable insights into the normal mechanisms regulating Bak activity.Read moreRead less
Computational systems biology: understanding mammalian cell fates using genome-scale network models. Mutations can disrupt the cellular networks that control normal development, causing cells to develop abnormally including in ways that lead to cancer. The project will analyse genome sequences from more than 700 pancreatic cancers and matched controls to precisely map the causative trail from mutations to disrupted networks to altered cell development.