Stem Cell Treatment For Neonatal Hypoxic Ischaemic Encephalopathy
Funder
National Health and Medical Research Council
Funding Amount
$954,195.00
Summary
Hypoxic-ischaemic encephalopathy occurs when the fetus receives inadequate oxygen in labour and many babies die or have brain damage. Stem cell therapy might save these babies from brain damage but there are many unknowns, such as which stem cells to use and how many. Through our skills in stem cells and measuring the rescued brain following injury, we will determine the necessary details for the most effective stem cell therapy to be ready to immediately test the treatment in a RCT in babies.
A Novel Mesenchymal Stromal Cell And Biomaterial For Corneal Reconstruction
Funder
National Health and Medical Research Council
Funding Amount
$508,611.00
Summary
Our research group has identified a new cell type (L-MSC) with the potential to treat a variety of eye diseases. We have also developed a novel material from a protein found in silk, that has potential as a vehicle for delivering healthy cells into diseased eyes. The present project will build upon these promising results by evaluating the properties of L-MSC necessary for clinical use and by testing the feasibility of our new cell delivery system.
Functional Contribution Of Fetal Microchimeric Cells In Transgenic Models Of Maternal Tissue Repair In And After Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$542,462.00
Summary
Fetal stem cells cross into the mother during pregnancy and persist lifelong in her tissues. To determine whether helpful or harmful, we will study how these cells contribute to healing both after acute injury and in chronic genetic models like brittle-bone disease and muscular dystrophy. This research will inform long-term consequences of pregnancy, important for women's health and longevity, and help develop a promising form of stem cell therapy.
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
Polarized Trafficking Of E-cadherin In Epithelial Cells.
Funder
National Health and Medical Research Council
Funding Amount
$515,564.00
Summary
The cell adhesion protein E-cadherin is expressed in all epithelial tissues of the body where it has essential functions during development and in the adult in establishing and maintaining polarized cell monolayers. E-cadherin is also a vital tumour suppressor, its normal function guarantees that cells or even early tumours cannot metastasise; in contrast E-cadherin is always lost or malfunctions in malignant tumours. Earlier studies showed that E-cadherin is constantly moved, or trafficked, to ....The cell adhesion protein E-cadherin is expressed in all epithelial tissues of the body where it has essential functions during development and in the adult in establishing and maintaining polarized cell monolayers. E-cadherin is also a vital tumour suppressor, its normal function guarantees that cells or even early tumours cannot metastasise; in contrast E-cadherin is always lost or malfunctions in malignant tumours. Earlier studies showed that E-cadherin is constantly moved, or trafficked, to and from the surface of epithelial cells. This trafficking has dual roles, firstly in delivering newly-made E-cadherin to the surface where it functions and secondly, in regulating its adhesive function. Our research in this project is focussed on the molecules and intracellular compartments that control the delivery of E-cadherin to the cell surface. E-cadherin must be sorted in order to be delivered to the correct side of the cell. Having previously discovered the sorting signal in E-cadherin, we will now identify the cognate adaptor protein(s) that accomplish this sorting. New imaging techniques allow us to study protein trafficking inside live cells. Such studies have recently revealed that E-cadherin passes through a recycling endosome compartment on its way to the cell surface. This unexpected route, and the structure and role of the recycling endosome will now be studied in detail in live cells. Finally we will compare the sorting and trafficking of E-cadherin with the closely-related N-cadherin protein, to determine whether there are inherent differences in their trafficking that could explain their opposite roles in tumour cells, where N-cadherin is substituted for E-cadherin and allows metastatic behaviour. These studies will provide important information for understanding the adhesive and tumour suppressive roles of E-cadherin. In addition our findings will generate information fundamental to our understanding of cell polarity and protein sorting.Read moreRead less
A Micro-Physiological System to Mimic Human Microbiome-Organ Interactions. This project aims to mimic gut microbiome-organ interactions by developing a microbial-gut coculture chip, which can reversibly interface with other organs-on-chips. This is achieved through the systematic integration of highly customisable biofabrication and microfluidic technologies. This project fills a critical technological gap in the availability of an animal-alternative system to investigate microbiome-host interac ....A Micro-Physiological System to Mimic Human Microbiome-Organ Interactions. This project aims to mimic gut microbiome-organ interactions by developing a microbial-gut coculture chip, which can reversibly interface with other organs-on-chips. This is achieved through the systematic integration of highly customisable biofabrication and microfluidic technologies. This project fills a critical technological gap in the availability of an animal-alternative system to investigate microbiome-host interactions, which will greatly complement existing meta-omics approaches. The deliverables include a proof-of-concept system validated for gut-liver axis as well as the creation of new knowledge and framework to assimilate design thinking and advanced manufacturing to elevate tissue engineering into physiology engineering. Read moreRead less
Understanding the differentiation of the endocardium. The project aims to understand the genetic regulation of endocardial development. The heart is essential for survival, its beat the indicator of life. The endocardium, the heart’s inner lining, is required for signalling during heart development and is a major component of the valves, septa and trabeculae. Despite its indispensable role, little is known about how it forms or develops. This project integrates two complementary approaches that ....Understanding the differentiation of the endocardium. The project aims to understand the genetic regulation of endocardial development. The heart is essential for survival, its beat the indicator of life. The endocardium, the heart’s inner lining, is required for signalling during heart development and is a major component of the valves, septa and trabeculae. Despite its indispensable role, little is known about how it forms or develops. This project integrates two complementary approaches that have identified the earliest marker of endocardial differentiation and devised the method to make endocardium from stem cells. Knowledge from this work will inform future research into growing and regenerating damaged tissue.Read moreRead less
Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family protei ....Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family proteins as specific effectors. This project will address a new paradigm in genetics that is likely to underpin development.Read moreRead less
Hypoxia-mimicking bio-scaffold for skeleton regeneration. The project is to develop bioactive bone grafts to improve bone repair and shorten the recovery time of patients with fractures, degenerative joint diseases, and bone cancer and bone deformities.
The development of new scaffolds for bone repair comprising polycaprolactone and strontium-substituted bioactive glasses. The drive to develop bone grafts to fill major gaps in the skeleton, whilst circumventing the need to use permanent implants has led to a major research thrust towards developing biomaterials for bone-tissue engineering. The project will develop scaffolds with highly osteoconductive bioactive glasses in a polymer matrix for bone regeneration applications.