Novel Transcription Factor Regulation Of Lymphatic Vascular Angiogenesis In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$831,568.00
Summary
Lymphatic vessels control tissue fluid drainage, inflammatory processes and cancer progression. We have used genetic approaches to discover an unexpected role for a family of factors (transcription factors) that regulate new lymphatic vessel formation. This project will investigate this biological function of these genes in detail in vascular formation. The project aims to generate important knowledge for vascular biology, vascular pathologies, cancer spread and future therapeutics.
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.
Investigating A Novel Genetic Regulator Of Cardiac Rhythm
Funder
National Health and Medical Research Council
Funding Amount
$557,101.00
Summary
Cardiac arrhythmias affect approximately 5% of the population and have a high association with sudden death. Whilst the cause of cardiac arrhythmia is complex, we know that genetic mutations play a role however we don't know all the genes important for cardiac rhythm. It is imperative that we identify all the genes in this process, so we can determine which mutations cause arrhythmia. We have identified a new gene that causes cardiac arrhythmia and seek to understand how it functions.
Many human muscle diseases are caused by mutations in genes encoding skeletal muscle actin. Actin is a major building block of the sarcomere, the engine of muscle contraction. Our studies have identified a mutation in chaperonin, the main protein-folding complex responsible for actin folding, which results in a muscle defect. These results have led to a novel hypothesesis, which we test in this grant, namely that as the chaperonin complex can act as a modulator of of muscle disease.
Determining The Pathobiology Of Human Sarcomeric Myopathies Using Zebrafish
Funder
National Health and Medical Research Council
Funding Amount
$509,541.00
Summary
Laing muscular dystrophy and ACTA1 congenital muscular dystrophy are severe muscle diseases with high morbidity. We will create zebrafish strains that carry these diseases and use these to understand the causes of muscle failure and investigate possible areas of treatment for these conditions.
Tissue-dependent Proregenerative Mechanisms In Adult Vertebrates
Funder
National Health and Medical Research Council
Funding Amount
$638,742.00
Summary
This proposal addresses how immune cells participate in regeneration of damaged organs in adult zebrafish. Unlike mammals, zebrafish have a remarkable capacity to regenerate their various body parts in adulthood, providing a model to understand how regeneration capacity might be induced in humans. The proposed study will define mechanisms of immune-mediated regeneration that could provide new cellular and molecular targets for stimulating replacement of damaged organs in the human injury setting
Identification And Characterisation Of Genes Required For Cardiac Morphogenesis
Funder
National Health and Medical Research Council
Funding Amount
$434,706.00
Summary
The heart is the first organ to become functional as an embryo forms, reflecting its critical role in sustaining life. Mistakes that occur as the heart develops have devastating consequences for an individualĂs survival and health. We have identified two zebrafish mutants with heart defects and, using sophisticated imaging and genetic studies, will investigate these defects and identify the genes responsible. This research will improve our understanding of correct and diseased heart formation.
Examining An Extracellular Matrix Regulator Required For Cardiovascular Development
Funder
National Health and Medical Research Council
Funding Amount
$732,600.00
Summary
Cardiovascular disease (CVD) is the highest cause of death in Australia. Specific genes are required for correct assembly and function of the heart and vessels but disease will result if those genes are defective. To diagnose and treat CVD, we must first understand how these genes function. This project will investigate mouse models with genetic defects resulting in CVD. It will determine how and why the diseases occur and investigate a potential therapeutic option for intervention in CVD.
Characterisation Of A Newly Identified, Indispensible, Transcriptional Regulator Of Lymphangiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$535,224.00
Summary
Lymphatic vessels form via lymphangiogenesis: growth of lymphatics from pre-existing vessels. This process is amenable to therapeutic intervention during metastasis because lymphatics support tumour spread. We discovered a gene that is essential for lymphangiogenesis to occur. We will investigate the control of lymphangiogenesis by this new factor. We aim to understand how it controls lymphatic vessel formation and identify genes within this pathway that have novel therapeutic potential.
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.