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Discovery And Analysis Of Vertebrate Intestinal Development Genes That May Play A Role In Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$376,613.00
Summary
Colorectal cancer (CRC) causes more cancer deaths in Australia than any other cancer. While early detection improves survival rate, nearly half of all CRC patients succumb to the disease within five years. In general, metastatic CRC is resistant to chemotherapy and radiotherapy and new therapies are required. An increased knowledge of the processes that contribute to the malignant state is likely to suggest new targets for treatment. CRC, like all cancer, is the result of genetic abnormalities ( ....Colorectal cancer (CRC) causes more cancer deaths in Australia than any other cancer. While early detection improves survival rate, nearly half of all CRC patients succumb to the disease within five years. In general, metastatic CRC is resistant to chemotherapy and radiotherapy and new therapies are required. An increased knowledge of the processes that contribute to the malignant state is likely to suggest new targets for treatment. CRC, like all cancer, is the result of genetic abnormalities (mutations) that are acquired over the course of a lifetime. Together the mutated genes produce changes in cell behaviour in processes such as growth, migration, angiogenesis (the ability to attract a blood supply) and cell death. All of these processes are active during normal development of a vertebrate organism, but are generally shutdown in the adult state, except in cancer. In this study we will analyse a group of genes that we have recently shown to be indispensable for normal intestinal development in zebrafish. Zebrafish are small tropical fish that are used frequently for genetic studies. They are very closely related to mammals and it has been shown that the genetic pathways that control the development of this animal are highly conserved in fish and mammals. Importantly, the genetic pathways that lead to cancer in humans are also strikingly similar in zebrafish. Our experiments will use mouse models to discover whether the zebrafish genes we have identified can lead to cancer when they are aberrantly expressed in the intestines of mice. Any genes that are found to contribute to the development of cancer in these models could become potential new targets for cancer therapy.Read moreRead less
The Role Of Rnpc3 In U12-type MRNA Splicing, Gene Expression And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$593,794.00
Summary
The zebrafish is a small tropical fish that is an alternative model to mice for genetic studies. We have used zebrafish to discover genes that are essential for the rapid development of the intestine in the belief that these genes are also essential for tumour growth. We will test whether the loss of RNPC3 (the human version of one of our genes), which is required for the production of a small number of proteins that can suppress the development of cancer, plays a hitherto unappreciated causal r ....The zebrafish is a small tropical fish that is an alternative model to mice for genetic studies. We have used zebrafish to discover genes that are essential for the rapid development of the intestine in the belief that these genes are also essential for tumour growth. We will test whether the loss of RNPC3 (the human version of one of our genes), which is required for the production of a small number of proteins that can suppress the development of cancer, plays a hitherto unappreciated causal role in the development of colon tumours.Read moreRead less
Cancer is linked to mutations in a large variety of genes but how these changes impact on cell behaviour is often unknown. We are using functional genomics in zebrafish to identify genes that are essential for rapid rates of proliferation by intestinal epithelial cells. Seven genes have been cloned so far and our next task is to analyse, using mouse models and human cancer transcriptome analysis, whether any are indispensable for cancer growth and thereby present suitable targets for therapy.
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
Identification And Characterization Of The Molecular Mechanisms Of Cardiac Muscle Regeneration Regulated By The Epicardium In Zebrafish
Funder
National Health and Medical Research Council
Funding Amount
$540,772.00
Summary
Heart attack is a life-threatening disease that damages cardiac muscle. The human heart cannot create new muscle after the damage, which partly contributes to the high morbidity and mortality of this disease. Unlike humans, zebrafish, a small tropical freshwater fish, can naturally create cardiac muscle after injury. In this project, we will understand at the molecular level how zebrafish regenerate cardiac muscle, and provide insights for repairing damaged muscle in the human heart.
The Genetic And Cellular Control Of Lymphangiogenesis In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$475,534.00
Summary
Lymphatic vessels and veins play major roles in cardiovascular disorders. In many vascular pathologies we need an ability to promote or restrict vessel formation. This research investigates the genes that control the development of new veins and lymphatic vessels. Outcomes will include a greater understanding of how our vasculature is formed, providing new knowledge that should contribute to future lymphatic and vascular therapeutic approaches.