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FUNCTIONAL ANALYSIS OF IGF-BINDING PROTEIN-2 MOLECULAR INTERACTIONS IN EARLY DEVELOPMENT AND DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$551,328.00
Summary
Early development involves complex regulation of cell and organ growth. Cell migration and invasion are critical components of epithelial-mesenchymal transition (EMT) essential for early developmental, as well as injury repair and cancer. Common to these events is a highly expressed protein, insulin-like growth factor binding protein-2 (IGFBP-2), which appears to play a critical role in regulating the processes of cell migration and invasion. The underlying mechanisms of cellular regulation by I ....Early development involves complex regulation of cell and organ growth. Cell migration and invasion are critical components of epithelial-mesenchymal transition (EMT) essential for early developmental, as well as injury repair and cancer. Common to these events is a highly expressed protein, insulin-like growth factor binding protein-2 (IGFBP-2), which appears to play a critical role in regulating the processes of cell migration and invasion. The underlying mechanisms of cellular regulation by IGFBP-2 are major focus of this proposal, which brings together four major groups focussed on early development, neural injury repair, and cancer biology. We will use a range of in vitro and in vivo approaches to determine the underlying mechanisms of action of this critical protein. This project has the potential to point to novel therapeutic modalities in development, repair and cancer.Read moreRead less
Kallikrein Gene Variants In Prostate Cancer: Analysis Of Gene Regulation And Diagnostic/Prognostic Use
Funder
National Health and Medical Research Council
Funding Amount
$486,801.00
Summary
Prostate cancer is the most common male cancer in Australia. However, early detection through screening programs has proven challenging, and about 30% of the 10,000 new cases diagnosed annually already have advanced disease. Hence, there is a fundamental need for increased basic research in prostate cancer etiology (cause) and tumour biology, and a critical requirement for methods that will assist in earlier detection of the disease and predict progression. A family of proteins called kallikrein ....Prostate cancer is the most common male cancer in Australia. However, early detection through screening programs has proven challenging, and about 30% of the 10,000 new cases diagnosed annually already have advanced disease. Hence, there is a fundamental need for increased basic research in prostate cancer etiology (cause) and tumour biology, and a critical requirement for methods that will assist in earlier detection of the disease and predict progression. A family of proteins called kallikreins (including prostate specific antigen, PSA) are often associated with clinical features of prostate cancer. We will characterise genetic variants (polymorphisms) in kallikrein genes that are consistently over-produced in prostate cancer, and determine whether they cause more protein to be produced in cells grown in the laboratory and in tumour tissue, and-or give rise to different expression products or splice variants. We will use bioinformatics (computer programs) to characterise published kallikrein gene sequences and to examine them for genetic variants that might be related to changes in gene expression or to splice variants. We will then use a case-control study, involving 1200 men with prostate cancer and 1200 healthy men, to determine whether these gene variants are associated with an increased risk of prostate cancer or with clinical aspects of the disease. Finally, we will examine the functional significance of the gene variants. This project represents an important and novel combination of molecular biology with the study of clinical disease at the population level, in the relatively new field of molecular epidemiology. It will clarify the role of kallikrein gene variants in prostate cancer risk and progression. The technologies may ultimately prove useful clinically for diagnosis of prostate cancer or for monitoring of treatment and prognosis, and hopefully will assist in clinical decision-making.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120100434
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Estrogen-mediated regulation of gene expression via transcriptional and translational control: complementary, synergistic or opposing responses? Hormones dictate cellular behaviour by activating pre-programmed responses. The sex hormone estrogen affects cell fate by regulating the gene expression, but it is unknown to which extent this response occurs via activation of genes or control of already transcribed gene. The project will investigate how the cell integrates the complex estrogen signals.