Hedgehog Signalling In Limb And Craniofacial Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$494,544.00
Summary
Anomalies of the face and limbs are amongst the most common features of human birth defects, and their frequent association suggests that the same genes are involved in governing the development of the limbs and face during embryogenesis. We have used a genomics-based approach to identify genes involved in limb development based on their alteration in a mouse model which develops extra fingers and toes. Defects in this mouse result from changes in Gli3, a gene which is known to be important in b ....Anomalies of the face and limbs are amongst the most common features of human birth defects, and their frequent association suggests that the same genes are involved in governing the development of the limbs and face during embryogenesis. We have used a genomics-based approach to identify genes involved in limb development based on their alteration in a mouse model which develops extra fingers and toes. Defects in this mouse result from changes in Gli3, a gene which is known to be important in both limb and face development. Based on the organs in which our genes of interest are active, we believe that they will also play key roles in embryonic development of the limbs, face and other organs. We now plan to investigate the regulation of a subset of these genes based on analysis in mouse models of limb and face development. In addition, we have chosen to further analyse the function of a completely novel gene we have identified which our preliminary studies suggest may play a role in the normal development of the lip and palate. These studies have the potential to shed light on the processes governing how organs develop, as well as on the molecular basis of common birth defects such as polydactyly (extra fingers and toes) and cleft palate.Read moreRead less
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.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100200
Funder
Australian Research Council
Funding Amount
$270,427.00
Summary
AutoStem: a high performance, automated stem cell bioengineering facility. This project aims to establish an automated stem cell bioengineering ("AutoStem") facility that will enable critical insights into the molecular mechanisms that underly the loss in stem cell function and tissue homeostasis as we age. The AutoStem facility expects to lead to the discovery of the key drivers of stem cell ageing and the development of novel technological solutions to maintain tissue function with age. The o ....AutoStem: a high performance, automated stem cell bioengineering facility. This project aims to establish an automated stem cell bioengineering ("AutoStem") facility that will enable critical insights into the molecular mechanisms that underly the loss in stem cell function and tissue homeostasis as we age. The AutoStem facility expects to lead to the discovery of the key drivers of stem cell ageing and the development of novel technological solutions to maintain tissue function with age. The outcomes produced from the AutoStem facility will have significant economic and social benefits in enabling healthy ageing and increased productivity for an ageing Australia.Read moreRead less
Astroglial Remodelling Of The Interhemispheric Midline Is Regulated By Deleted In Colorectal Cancer (DCC) Signalling And Is Required For Corpus Callosum Formation
Funder
National Health and Medical Research Council
Funding Amount
$669,400.00
Summary
The integration of information between the brain hemispheres occurs via a large bundle of connecting nerve fibres called the corpus callosum. People with a genetic mutation in DCC display mirror movement disorder and some have a severe brain defect where the corpus callosum fails to form, but at present we don’t understand the function of this gene. In this study we will investigate how DCC functions in early brain development to regulate corpus callosum formation and mirror movement disorder.
Redefining tissue-specific endothelial cells through bioengineered matrices. This project aims to improve our understanding of the biological mechanisms that drive blood vessel formation and function. The endothelial cells that make up each blood vessel are inherently unique across different sites within the human body and this project expects to generate new knowledge regarding their organ specificity. Using advanced bioengineering approaches, this project will map human endothelial cell specif ....Redefining tissue-specific endothelial cells through bioengineered matrices. This project aims to improve our understanding of the biological mechanisms that drive blood vessel formation and function. The endothelial cells that make up each blood vessel are inherently unique across different sites within the human body and this project expects to generate new knowledge regarding their organ specificity. Using advanced bioengineering approaches, this project will map human endothelial cell specificity and develop state-of-the-art modelling technologies to improve knowledge of environmental influence on endothelial cell fate and function. This should provide a new framework to modulate the adaptive capacities of endothelial cells and can potentially enable more predictive and targeted drug efficacy and safety testing.Read moreRead less
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
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