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.
E-Cadherin Endocytosis In Morphogenesis: Recycling And Growth Factor Induced Uptake.
Funder
National Health and Medical Research Council
Funding Amount
$498,088.00
Summary
E-cadherin is a cell-cell adhesion protein expressed in all epithelia with essential roles in establishing cell polarity and in tissue patterning during development. In the adult, E-cadherin functions to maintain epithelial integrity. E-cadherin is also a vital tumour suppressor, protecting cells against metastatic transformation. Our earlier studies showed that E-cadherin is constantly moved, or trafficked, to and from the surface of epithelial cells. The endocytosis or internalisation of cell ....E-cadherin is a cell-cell adhesion protein expressed in all epithelia with essential roles in establishing cell polarity and in tissue patterning during development. In the adult, E-cadherin functions to maintain epithelial integrity. E-cadherin is also a vital tumour suppressor, protecting cells against metastatic transformation. Our earlier studies showed that E-cadherin is constantly moved, or trafficked, to and from the surface of epithelial cells. The endocytosis or internalisation of cell surface E-cadherin serves to regulate its role in adhesion. More recently, we and others have shown that E-cadherin is endocytosed in response to growth factors, in conjunction with the activated growth factor receptors themselves. E-cadherin can influence the trafficking and signaling of these receptor tyrosine kinases. This joint endocytosis is an elegant mechanism for the simultaneous downregulation of cell adhesion and activation of signaling for cell growth and motility. The growth and differentiation of epithelial cells during tissue patterning or morphogenesis relies critically on these endocytic pathways. Our research is aimed at defining the endosomes and cellular machinery involved in E-cadherin-receptor endocytosis, moreover we will pursue initial findings suggesting that there are different pathways and fates for E-cadherin endocytosed at the behest of different growth factors. We will study endocytosis during the processes of epithelial cyst formation and tubulation of cysts as an in vitro model for mammalian morphogenesis. These studies will provide important and novel information for understanding the roles of E-cadherin in adhesion and in growth factor signaling during epithelial morphogenesis. Ultimately these findings will be of relevance to epithelial development and the prevention of cancer.Read moreRead less
Advanced solar powered hydrogen production systems based on green algal cells. This project aims to enhance the efficiency of solar powered hydrogen production from water and will facilitate the co-production of H2 and oil through microalgal biofuel systems. This frontier science project will therefore deliver a process with high solar conversion efficiency and will deliver multiple product streams increasing profitability.
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.
Half a Genome is Better than None: The Evolution of Haplodiploidy in Mites. It is our normal experience that males and females are about equally common. We also expect both sexes to receive half their genes from each parent. In many successful animal groups, however, these normal expectations are not met: males are rare and have only half as many chromosomes as females (haplodiploidy) or are non-existent. We will investigate multiple origins of haplodiploid and all-female genetic systems in a ....Half a Genome is Better than None: The Evolution of Haplodiploidy in Mites. It is our normal experience that males and females are about equally common. We also expect both sexes to receive half their genes from each parent. In many successful animal groups, however, these normal expectations are not met: males are rare and have only half as many chromosomes as females (haplodiploidy) or are non-existent. We will investigate multiple origins of haplodiploid and all-female genetic systems in a group of mites that includes many useful biocontrol agents and important parasites. The implications of this research have both pure scientific merit and potential practical value in controlling the reproduction of pests.Read moreRead less
Targeting mitochondria with mitocans to treat cancer: mechanistic aspects. Mitochondria are the power-house of the cell and also the reservoir of proteins causing the demise of cancer cells, therefore suppressing tumour progression. This project proposes a novel way to modify certain compounds, increasing their level in mitochondria in order to maximise their anti-cancer effect.
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.
Discovery Early Career Researcher Award - Grant ID: DE240100561
Funder
Australian Research Council
Funding Amount
$462,237.00
Summary
Understanding how platelets mediate new neuron formation in the adult brain. Exercise boosts the generation of new nerve cells from adult neural stem cells in the part of the brain responsible for learning and memory, the hippocampus. This project aims to investigate the mechanisms behind this effect, in particular, how blood cells known as platelets mediate this process. The expected outcomes include the discovery of new communication pathways between platelets and the brain following exercise ....Understanding how platelets mediate new neuron formation in the adult brain. Exercise boosts the generation of new nerve cells from adult neural stem cells in the part of the brain responsible for learning and memory, the hippocampus. This project aims to investigate the mechanisms behind this effect, in particular, how blood cells known as platelets mediate this process. The expected outcomes include the discovery of new communication pathways between platelets and the brain following exercise and will determine the importance of these blood cells in mediating brain function. This will help to explain how exercise affects the brain and may benefit Australian society through the implementation of new methods to support learning and memory in schools and workplaces, thereby enhancing performance and productivity.Read moreRead less
Coral Reefs Sensing Our Changing Climate. Australia's Great Barrier Reef is a valuable national and community resource, supporting commercial and recreation fishing and extensive national and international tourism along the length of Queenslands coastline. However it is an environment that is under threat from changing climate. The impact of a degraded reef environment is broad reaching, with effects on the Australian and Queensland economy and way of life. A better understanding of how this va ....Coral Reefs Sensing Our Changing Climate. Australia's Great Barrier Reef is a valuable national and community resource, supporting commercial and recreation fishing and extensive national and international tourism along the length of Queenslands coastline. However it is an environment that is under threat from changing climate. The impact of a degraded reef environment is broad reaching, with effects on the Australian and Queensland economy and way of life. A better understanding of how this valuable environment will respond to its changing environment is imperative and will provide us with a more informed basis on which to predict its future sustainability. Read moreRead less
A conserved pathway of cell death in response to invading DNA. This project aims to characterise molecular details of a new pathway of foreign DNA recognition and rapid cell death. Recognition of foreign DNA is a key means by which both bacteria and eukaryotic cells can detect infections, as well as guard their own genome. Eukaryotic cell DNA is sequestered in the nucleus and organelles, and any DNA found in the cytosol is a danger signal. The project proposes that cytosolic DNA-induced cell dea ....A conserved pathway of cell death in response to invading DNA. This project aims to characterise molecular details of a new pathway of foreign DNA recognition and rapid cell death. Recognition of foreign DNA is a key means by which both bacteria and eukaryotic cells can detect infections, as well as guard their own genome. Eukaryotic cell DNA is sequestered in the nucleus and organelles, and any DNA found in the cytosol is a danger signal. The project proposes that cytosolic DNA-induced cell death is a fundamental eukaryotic defensive response, but surprisingly, the known pathway is restricted to macrophages of some mammals. Project outcomes may be applied to protein expression yield in biotechnology or advances in gene therapy.Read moreRead less