I am a developmental cell biologist and molecular geneticist focusing on mechanisms controlling cell proliferation and modelling the development of cancer in the vinegar fly, Drosophila.
A major feature of tumour progression and cardiac hypertrophy (enlarged heart) is accelerated cell growth and protein synthesis. Moreover, increased synthesis of ribosomes (the protein synthetic machinery) is associated with malignancy and hypertrophy suggesting that it may play a causal role in tumour formation and cardiac disease. In support of this, specific inhibitors of both ribosome biogenesis and function are extremely effective at inhibiting the growth of some tumours and vascular smooth ....A major feature of tumour progression and cardiac hypertrophy (enlarged heart) is accelerated cell growth and protein synthesis. Moreover, increased synthesis of ribosomes (the protein synthetic machinery) is associated with malignancy and hypertrophy suggesting that it may play a causal role in tumour formation and cardiac disease. In support of this, specific inhibitors of both ribosome biogenesis and function are extremely effective at inhibiting the growth of some tumours and vascular smooth muscle. This study will examine the mechanisms that regulate ribosome synthesis. Specifically it focuses on a transcription factor termed UBF whose activity we think is critical for the regulation of the synthesis of the ribosomal RNA, the catalytic backbone of the ribosomes. Understanding the molecular mechanism(s) controlling UBF function will lead to a better comprehension of how cells modulate synthesis of functional ribosomes and how this process is deregulated during disease states associated with deregulated protein synthesis and growth such as cardiac hypertrophy and cancer.Read moreRead less
Deregulation Of Ribosome Signalling, Synthesis And Function During Malignant Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$522,773.00
Summary
A major feature of tumour progression is accelerated cell growth and protein synthesis. Moreover, increased synthesis of ribosomes (the protein synthetic machinery) is associated with malignancy suggesting that it may play a causal role in cancer formation. In support of this, specific inhibitors of both ribosome biogenesis and function are extremely effective in inhibiting the growth of some tumours. This study will examine the mechanisms of deregulation of ribosome biogenesis and function duri ....A major feature of tumour progression is accelerated cell growth and protein synthesis. Moreover, increased synthesis of ribosomes (the protein synthetic machinery) is associated with malignancy suggesting that it may play a causal role in cancer formation. In support of this, specific inhibitors of both ribosome biogenesis and function are extremely effective in inhibiting the growth of some tumours. This study will examine the mechanisms of deregulation of ribosome biogenesis and function during cancer formation and assess for the first time whether aberrant regulation of ribosome biogenesis and function directly contributes to the initiation and-or progression of cancer.Read moreRead less
Novel cell wall genes ripe for the picking. This project aims to investigate the role of recently discovered plant cellulose synthase-like CslM genes and to define the polysaccharide product associated with them. Successful identification of the polysaccharide is highly likely to increase our fundamental understanding of how cell walls are made, how cells stick together or fall apart as well as facilitating the training of the next generation of cell wall biologists in challenging molecular and ....Novel cell wall genes ripe for the picking. This project aims to investigate the role of recently discovered plant cellulose synthase-like CslM genes and to define the polysaccharide product associated with them. Successful identification of the polysaccharide is highly likely to increase our fundamental understanding of how cell walls are made, how cells stick together or fall apart as well as facilitating the training of the next generation of cell wall biologists in challenging molecular and biochemical techniques. This new knowledge could increase our understanding of fruit ripening, and how it might be manipulated. This could have significant downstream commercial benefits if applied to breeding programs of economically important fruit such as grapes, tomatoes and strawberries.Read moreRead less
Predicting cell wall mechanics from structure in a materials engineering approach to plant growth. The project fosters a novel, interdisciplinary approach to understanding how the structure of plant cell walls determines their mechanical properties. Such understanding requires combining biological and engineering approaches and will illuminate how plants grow and produce cells and organs with particular shapes. This is scientifically important but is also important for industries depending on sp ....Predicting cell wall mechanics from structure in a materials engineering approach to plant growth. The project fosters a novel, interdisciplinary approach to understanding how the structure of plant cell walls determines their mechanical properties. Such understanding requires combining biological and engineering approaches and will illuminate how plants grow and produce cells and organs with particular shapes. This is scientifically important but is also important for industries depending on specialised cell shapes such as those of cotton and wood fibres. Our work will improve our understanding of how wall structure determines fibre and other cell shapes and give us tools which can be used to understand how final wall structure determines the fibre mechanics on which industrial users depend. Read moreRead less
The molecular role of ADAM12 in maintenance of skeletal muscle, myogenesis and adipogenesis. An understanding of the molecular control of skeletal muscle growth, maintenance and balance between muscle and fat production is of fundamental importance for a competitive meat industry, for the promotion of strong muscles in the ageing population and for disorders such as muscle diseases, diabetes and obesity. This project will enhance strong international collaborations and expand cutting-edge resear ....The molecular role of ADAM12 in maintenance of skeletal muscle, myogenesis and adipogenesis. An understanding of the molecular control of skeletal muscle growth, maintenance and balance between muscle and fat production is of fundamental importance for a competitive meat industry, for the promotion of strong muscles in the ageing population and for disorders such as muscle diseases, diabetes and obesity. This project will enhance strong international collaborations and expand cutting-edge research within Australia with many potential economic benefits for the meat industry, biotechnology and health. The expertise developed by this pioneering research will ensure that Australia is well placed to harness new technologies and exploit future advances in this fast-moving field of muscle biology.Read moreRead less
Investigation of the biochemical and physiological functions of the negative regulator of cytokine signalling SOCS-2. Cytokines exert their effects by binding and signalling through specific cell surface receptors to elicit their biological action, and if left unchecked, this signalling can cause significant tissue damage and toxicity. Our aim is to characterise a novel regulator of cytokine signalling, SOCS-2. SOCS-2 is strongly implicated in the regulation of post-natal growth as SOCS-2 defici ....Investigation of the biochemical and physiological functions of the negative regulator of cytokine signalling SOCS-2. Cytokines exert their effects by binding and signalling through specific cell surface receptors to elicit their biological action, and if left unchecked, this signalling can cause significant tissue damage and toxicity. Our aim is to characterise a novel regulator of cytokine signalling, SOCS-2. SOCS-2 is strongly implicated in the regulation of post-natal growth as SOCS-2 deficient animals are 40 percent larger than normal. Consequently, we wish to determine how SOCS-2 acts to limit the size of an animal and whether this involves regulation of growth hormone action.Read moreRead less
Tyrosine Kinases And Phosphatases In Cell Cycle Checkpoint Responses
Funder
National Health and Medical Research Council
Funding Amount
$513,946.00
Summary
In order for an organism to grow and develop, the cells that make up the tissues and organs need to undergo a process of cellular division, wherein individual cells grow and then divide into two cells. During this process of cellular growth and division the entire genome needs to be duplicated (this occurs during S-phase) and then divided equally into the two daughter cells. In S-phase several so-called 'checkpoint' mechanisms exist which ensure that this occurs in an orderly and precise manner. ....In order for an organism to grow and develop, the cells that make up the tissues and organs need to undergo a process of cellular division, wherein individual cells grow and then divide into two cells. During this process of cellular growth and division the entire genome needs to be duplicated (this occurs during S-phase) and then divided equally into the two daughter cells. In S-phase several so-called 'checkpoint' mechanisms exist which ensure that this occurs in an orderly and precise manner. The so-called 'DNA replication checkpoint' delays S-phase progression in response to 'replication stresses' that may otherwise cause DNA damage. Protein tyrosine kinases (PTKs) are hyperactivated in many human solid tumours and blood malignancies contributing to varied aspects of tumour progression. Our preliminary studies indicate that the inactivation of PTKs by protein tyrosine phosphatases may be essential for the suppression of S-phase progression in response to replication stress. Our goal is to understand the molecular mechanisms by which PTKs and tyrosine phosphatases contribute to S-phase checkpoints. Our studies will provide important insights into DNA replication stress-induced checkpoint responses in mammals and identify unprecedented mechanisms by which hyperactivated PTKs may contribute to tumour development.Read moreRead less
Dissecting a hematopietic transcription factor complex. The development of mature active cells is a highly complex and coordinated process that is controlled largely by groups of interacting regulatory proteins. We are trying to understand, at a very detailed level, how a specific group of these proteins interact to regulate both normal blood cell development and the onset of childhood leukemias. Using this information we will try to develop reagents that can be used to inhibit these interaction ....Dissecting a hematopietic transcription factor complex. The development of mature active cells is a highly complex and coordinated process that is controlled largely by groups of interacting regulatory proteins. We are trying to understand, at a very detailed level, how a specific group of these proteins interact to regulate both normal blood cell development and the onset of childhood leukemias. Using this information we will try to develop reagents that can be used to inhibit these interactions and be used as lead compounds for treatments for disease.Read moreRead less