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Regulatory Interactions Between YAP And Beta-catenin In Normal Epidermal Homeostasis And In Skin Cancer
Funder
National Health and Medical Research Council
Funding Amount
$396,157.00
Summary
Australia has the highest skin cancer incidence in the world. We found that oncoprotein YAP activates stem cell proliferation in the skin through activation of the Wnt pathway, and we have evidence that YAP is hyperactivated in human skin cancer. We will map out the molecular nature of the interaction between YAP and the Wnt pathway in normal epidermal homeostasis and in skin cancer. This study will provide novel insights for development of therapeutic avenues for human skin cancer and other reg ....Australia has the highest skin cancer incidence in the world. We found that oncoprotein YAP activates stem cell proliferation in the skin through activation of the Wnt pathway, and we have evidence that YAP is hyperactivated in human skin cancer. We will map out the molecular nature of the interaction between YAP and the Wnt pathway in normal epidermal homeostasis and in skin cancer. This study will provide novel insights for development of therapeutic avenues for human skin cancer and other regenerative dermatological disorders.Read moreRead less
Defects In Epidermal Morphogenesis In Mammalian Grainyhead-like Gene Deficient Mice
Funder
National Health and Medical Research Council
Funding Amount
$623,065.00
Summary
The cells of the skin play an essential role in development of the mammalian embryo. They are critical for closure of the brain and spinal cord, for forming a protective barrier against infection and noxious stimuli, for preventing excess fluid loss, for repair of defects and wounds, and for the generation of hair. Our laboratory has identified a family of genes that are critical for all these processes. Loss of individual members of the family has different consequences and the aim of this stud ....The cells of the skin play an essential role in development of the mammalian embryo. They are critical for closure of the brain and spinal cord, for forming a protective barrier against infection and noxious stimuli, for preventing excess fluid loss, for repair of defects and wounds, and for the generation of hair. Our laboratory has identified a family of genes that are critical for all these processes. Loss of individual members of the family has different consequences and the aim of this study is to determine the relationship between the genes to further our understanding of the skin and its functions. These studies have direct and important relevance to human conditions such as the congenital birth defects spina bifida and anencephaly, and infant prematurity where the skin is underdeveloped and lacks barrier function. They also have relevance to wound healing and to conditions in which hair growth is affected, such as alopecia. We believe that therapeutic interventions and prenatal diagnostic tests could evolve from these studies.Read moreRead less
Identification Of Factors Critical For Maintenance Of The Epidermal Barrier
Funder
National Health and Medical Research Council
Funding Amount
$616,950.00
Summary
The human skin plays a crucial role in the body’s defence against our hostile environment. The outer most layer of the skin, the epidermis is the key structural component of the skin barrier and is essential for its integrity. We have identified a family of genes that are pivotal for epidermal barrier formation, maintenance and repair. This project examines the mechanisms that underpin the function of this family, and has broad ramifications in a host of dermatological conditions.
Using mouse genetics to understand skin development and cell biology. During embryonic development the skin forms a protective barrier which permits life outside the womb and provides a window into the biology of cells. This project aims to use the skin to identify and characterise genes necessary for embryonic development and maintenance, the development of diseases and to explore their broader roles in other organs.
A Critical New Signaling Axis In Lymphatic Vascular Angiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$700,784.00
Summary
The lymphatic vasculature is a crucial part of our vascular system required for tissue fluid drainage and maintenance of fluid homeostasis. Lymphatic vessels play major roles in vascular pathologies and in the spread of solid tumours during cancer progression. We have discovered a new molecular regulator controlling the formation of lymphatic vessels. This project will determine the signalling pathway employed by this new regulator and potential for future therapeutic applications.
Genetic And Metabolic Control Of Pancreatic Acinar To Beta Cell Transdifferentiation
Funder
National Health and Medical Research Council
Funding Amount
$375,817.00
Summary
Diabetes occurs when the cells in the pancreas that produce insulin are destroyed by the immune system or fail to keep up with demand. We have developed a method for converting other pancreatic cell types into insulin producing cells. The proposed research aims to improve the efficiency of our approach and to test its therapeutic potential in preclinical diabetes models.
Identifying Genes Required For Vertebral Column And Heart Formation
Funder
National Health and Medical Research Council
Funding Amount
$950,418.00
Summary
Birth defects occur in about 3% of live births. These originate as the embryo forms, and we have previously shown that some of these are caused by gene mutation and/or environmental factors during gestation. However, the origins of many such defects remain unexplained. We will examine the DNA of patients to find gene mutations causing such defects. We will also test if mutations in these genes increase the likelihood of the embryo developing a defect if it is exposed to environmental stressors.
The Role Of Innate Immune Responses In Cardiac Muscle Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$543,678.00
Summary
Heart attack is a life-threatening disease that damages heart muscle. Zebrafish can naturally restore lost heart muscle after injury, providing a model to understand mechanisms of heart regeneration. Here, we will explore previously uncharacterized events involved in heart regeneration, with particular focus on the immune response. We will study how immune responses are involved in heart muscle regeneration in zebrafish to find new insights for repairing damaged muscle in the human heart.
Australian Laureate Fellowships - Grant ID: FL180100019
Funder
Australian Research Council
Funding Amount
$2,906,976.00
Summary
An in situ structural study of Drosophila embryonic patterning. This project aims to develop and deploy an in situ structural biology approach, which enables direct visualisation of large macromolecular structures in cells, to be used in combination with molecular genetics, proteomics and computational biology. In situ structural biology has the potential to revolutionise discovery across life science, providing direct insight into macromolecular structure and function. This project will establi ....An in situ structural study of Drosophila embryonic patterning. This project aims to develop and deploy an in situ structural biology approach, which enables direct visualisation of large macromolecular structures in cells, to be used in combination with molecular genetics, proteomics and computational biology. In situ structural biology has the potential to revolutionise discovery across life science, providing direct insight into macromolecular structure and function. This project will establish the field of in situ structural biology in Australia by studying how a model organism, the fruit fly Drosophila melanogaster controls the development of how the head and tail of the embryo are specified. The project will further develop new instrumentation and approaches that will bring in situ biology to the wider scientific community.Read moreRead less