Defining The Role Of Glycosylation In Basement Membrane Failure During Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$824,664.00
Summary
This project aims to utilize mutations within the zebrafish fkrp gene to understand the pathogenic basis of the human diseases associated with mutation of this gene which results in a spectrum of muscular dystrophies. By generating models of alleles that represent the range of phenotypes seen in humans we will have a directly translatable model system to human pathology.
Understanding how the brain grows and is organised is one of the great challenges of science. This project seeks to identify key regulators of neural progenitors as these are the building blocks from which all brains cells are derived. This knowledge may also identify new avenues through which to manipulate neural progenitor function. This has implications not only for normal brain development but also potential therapies for neural disorders and disease.
Microtubule structure in nervous system repair. This Project aims to investigate the role of structural and functional cellular components known as microtubules in nervous system regeneration. This Project aims to use innovative approaches in confocal and electron microscopy, genetics, and cell biology, with the expectation of generating new knowledge into nervous system repair. Expected outcomes of this Project include a comprehensive description of how microtubules are rearranged following ner ....Microtubule structure in nervous system repair. This Project aims to investigate the role of structural and functional cellular components known as microtubules in nervous system regeneration. This Project aims to use innovative approaches in confocal and electron microscopy, genetics, and cell biology, with the expectation of generating new knowledge into nervous system repair. Expected outcomes of this Project include a comprehensive description of how microtubules are rearranged following nervous system injury and the importance of microtubule modifying proteins in promoting regeneration. This should provide significant benefits in our understanding of the cellular mechanisms behind nervous system repair, and offer new approaches for promoting regeneration after injury.Read moreRead less
How cell shape regulators control cell competition in tissue development. This project aims to determine how cell shape (polarity) regulators affect cell survival in an epithelial tissue. When mutation or wounding perturb cell shape regulators in a tissue cell, signalling pathways are altered that kill the aberrant cells. A surveillance mechanism termed "cell competition" is important to remove the damaged cells. This project will investigate a potential regulator of cell competition, the tyrosi ....How cell shape regulators control cell competition in tissue development. This project aims to determine how cell shape (polarity) regulators affect cell survival in an epithelial tissue. When mutation or wounding perturb cell shape regulators in a tissue cell, signalling pathways are altered that kill the aberrant cells. A surveillance mechanism termed "cell competition" is important to remove the damaged cells. This project will investigate a potential regulator of cell competition, the tyrosine phosphatase PTP61F, in response to perturbation of cell shape regulators, using the vinegar fly, Drosophila, and mammalian systems. This study is expected to reveal biomarkers that can be used to improve organismal fitness to increase productivity or to decrease it for pest control.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210100604
Funder
Australian Research Council
Funding Amount
$436,600.00
Summary
How do cells sense and react to mechanical forces? There is accumulating evidence that mechanical forces exerted on tissues and cells strongly influences their behaviour. My research aims to understand how cells sense and respond to forces experienced throughout life. Using a combination of three-dimensional cell and tissue culture methods, I will investigate how compressive forces change the biochemistry of cells and their functionality. This work is aimed at generating fundamental knowledge to ....How do cells sense and react to mechanical forces? There is accumulating evidence that mechanical forces exerted on tissues and cells strongly influences their behaviour. My research aims to understand how cells sense and respond to forces experienced throughout life. Using a combination of three-dimensional cell and tissue culture methods, I will investigate how compressive forces change the biochemistry of cells and their functionality. This work is aimed at generating fundamental knowledge to improve our comprehension of how cells respond to force. The expected outcome is a greater understanding of mechanical and biochemical relationships between cells and the environment, to inform fields of tissue engineering of culture scaffolds to better mimic natural cell-tissue settings.Read moreRead less
Defining The Role Of VEGF And Vascular Formation In Craniofacial Development
Funder
National Health and Medical Research Council
Funding Amount
$636,417.00
Summary
Aberrant neural crest cell development gives rise to common congenital malformations such as cleft lip and/or palate and cardiac outflow tract defects that effect over 1% of all births. As the aetiology of these disorders are largely unknown it is critical to understand the cell and molecular mechanisms coordinating NCC development such that alternative therapies may be devised to target the underlying pathological defects and to provide definitive diagnostic / prognostic tools.
Imaging the generation and recall of protective antiviral immune responses in vivo. Our understanding of the in vivo dynamics of cellular immune responses to infectious diseases is poor. This project will utilise advanced intravital imaging combined with novel tools to dissect the cellular events involved in the generation and recall of T cell responses to localised virus infection, combined with a detailed functional analysis of the lymphoid organ stroma. Such fundamental information will contr ....Imaging the generation and recall of protective antiviral immune responses in vivo. Our understanding of the in vivo dynamics of cellular immune responses to infectious diseases is poor. This project will utilise advanced intravital imaging combined with novel tools to dissect the cellular events involved in the generation and recall of T cell responses to localised virus infection, combined with a detailed functional analysis of the lymphoid organ stroma. Such fundamental information will contribute to the development of new generation vaccines and therapies to protect against tissue-specific infectious diseases, cancers and autoimmune diseases.Read moreRead less
Determining The Role Of Rel/NF-kB Transcription Factors In Myeloid Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$500,944.00
Summary
Different types of mature blood cells arise from stem cells in a process involving changes in gene expression that dictate which types of blood cells ultimately develop. A family of gene regulatory proteins called NF-kB transcription factors has been found to control the pattern of gene expression in a particular blood cell precursor called a granulocyte macrophage precursor (GMP) that normally generates two types of mature blood cells called macrophages and neutrophils. In the absence of NF-kB ....Different types of mature blood cells arise from stem cells in a process involving changes in gene expression that dictate which types of blood cells ultimately develop. A family of gene regulatory proteins called NF-kB transcription factors has been found to control the pattern of gene expression in a particular blood cell precursor called a granulocyte macrophage precursor (GMP) that normally generates two types of mature blood cells called macrophages and neutrophils. In the absence of NF-kB proteins, a change in the pattern of gene expression in GMPs leads to an imbalance in production of these two blood cell types that now favours the generation of neutrophils. This work will provide insight into the molecular mechanisms of blood cell development regulated by NF-kB. With disturbances in the balance of blood cell formation representing a hallmark of leukemia, understanding how this process is normally controlled may have important implications for developing therapeutic strategies to combat various types of leukemias.Read moreRead less
Understanding how the heart becomes more efficient. The body demands that the heart function at utmost efficiency. Trabeculae – folds within the heart lumen – maximise blood flow, contribute to chamber development and form the electrical conduction network of the heart. Problems with trabeculae formation cause cardiomyopathy and arrhythmia and yet we do not understand its basic development. The project will investigate the earliest stages of when this tissue develops its identity and examine the ....Understanding how the heart becomes more efficient. The body demands that the heart function at utmost efficiency. Trabeculae – folds within the heart lumen – maximise blood flow, contribute to chamber development and form the electrical conduction network of the heart. Problems with trabeculae formation cause cardiomyopathy and arrhythmia and yet we do not understand its basic development. The project will investigate the earliest stages of when this tissue develops its identity and examine the signalling, genetic, cellular and extracellular cues required to instruct trabeculae to form in the heart. Findings from this research will revise our understanding of when and how trabeculae form and provide key information about how to grow and repair this important tissue.Read moreRead less
Angiogenic defects in mutant growth plate cartilage reveal new modulators of vascular invasion. Converting cartilage to bone requires blood vessel invasion from the bony interface. This project will test, in vitro and in vivo, the hypothesis that collagen fragments regulate blood vessel invasion into cartilage. This data will have implications for processes requiring new blood vessels such as bone growth, cancer, inflammation and ischemia.