Role Of IGF Binding Protein-3 (IGFBP-3) And IGFBP-5 As Modulators Of Nuclear Hormone Signalling
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain ....The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain cells perform specialised functions. In test-tube experiments, IGFBP-3 and IGFBP-5 interact directly with the receptors that regulate the effects of these hormones. If the same thing happens inside the cell, IGFBP-3 and IGFBP-5 could change the way these receptors respond to signals from outside the cell. We will investigate what effect these IGFBPs have in living cells and in whole animals and how this may relate to human disease. If we are able to understand how IGFBP-3 and IGFBP-5 affect the way cells respond to vitamin A and D, then we may be able to develop new ways to treat certain human diseases.Read moreRead less
SARA: Delineating Its Association With The Onset And Development Of Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$865,972.00
Summary
Liver disease, a significant burden on society, affects many in the prime of their life. Scarring of the liver is a response to injury due to many factors including alcohol, viruses, obesity, and fatty-liver disease. We have identified a protein associated with liver injury. In this project we will perform a systematic analysis to understand the role of this protein in injury progression. Ultimately we intend to develop tools to prevent and treat liver injury.
Molecular Regulation Of Metabolism And Body Composition By Ski Via Crosstalk With Nuclear Hormone Receptor Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$558,441.00
Summary
Obesity is a common and burdensome health problem in the community which leads to diabetes and heart disease. A number of factors, including hormones play important roles in determing risk of obesity. This study proposes to investigate whether the Ski gene which is a regulatory factor for many hormones affects metabolism in transgenic mouse models of altered Ski function. The proposed studies may identify Ski as a target for therapy for obesity and improvement in sketal muscle metabolism.
Polarized Trafficking Of E-cadherin In Epithelial Cells.
Funder
National Health and Medical Research Council
Funding Amount
$515,564.00
Summary
The cell adhesion protein E-cadherin is expressed in all epithelial tissues of the body where it has essential functions during development and in the adult in establishing and maintaining polarized cell monolayers. E-cadherin is also a vital tumour suppressor, its normal function guarantees that cells or even early tumours cannot metastasise; in contrast E-cadherin is always lost or malfunctions in malignant tumours. Earlier studies showed that E-cadherin is constantly moved, or trafficked, to ....The cell adhesion protein E-cadherin is expressed in all epithelial tissues of the body where it has essential functions during development and in the adult in establishing and maintaining polarized cell monolayers. E-cadherin is also a vital tumour suppressor, its normal function guarantees that cells or even early tumours cannot metastasise; in contrast E-cadherin is always lost or malfunctions in malignant tumours. Earlier studies showed that E-cadherin is constantly moved, or trafficked, to and from the surface of epithelial cells. This trafficking has dual roles, firstly in delivering newly-made E-cadherin to the surface where it functions and secondly, in regulating its adhesive function. Our research in this project is focussed on the molecules and intracellular compartments that control the delivery of E-cadherin to the cell surface. E-cadherin must be sorted in order to be delivered to the correct side of the cell. Having previously discovered the sorting signal in E-cadherin, we will now identify the cognate adaptor protein(s) that accomplish this sorting. New imaging techniques allow us to study protein trafficking inside live cells. Such studies have recently revealed that E-cadherin passes through a recycling endosome compartment on its way to the cell surface. This unexpected route, and the structure and role of the recycling endosome will now be studied in detail in live cells. Finally we will compare the sorting and trafficking of E-cadherin with the closely-related N-cadherin protein, to determine whether there are inherent differences in their trafficking that could explain their opposite roles in tumour cells, where N-cadherin is substituted for E-cadherin and allows metastatic behaviour. These studies will provide important information for understanding the adhesive and tumour suppressive roles of E-cadherin. In addition our findings will generate information fundamental to our understanding of cell polarity and protein sorting.Read moreRead less
EPIGENETIC REPROGRAMMING OF MALIGNANT BREAST CANCER
Funder
National Health and Medical Research Council
Funding Amount
$863,268.00
Summary
Poorly differentiated breast cancers are aggressive tumors, frequently resistant to chemotherapy and associated with high morbidity. Herein we propose the engineering of more selective therapeutic agents able to target the genes involved in cancer initiation and resistance to treatment. We aim to correct and reprogram the cancer cell genome in state that is similar to normal, not tumorigenic cells. This work will generate novel forms of treatment for cancers that are presently not curable.
Discovery Early Career Researcher Award - Grant ID: DE200100345
Funder
Australian Research Council
Funding Amount
$384,616.00
Summary
Harnessing nanotechnology to unravel extracellular vesicle heterogeneity. This project aims to develop a suite of innovative nanotechnologies to study extracellular vesicles with unprecedented depth of analysis and single particle resolution. This project expects to generate new knowledge in the emerging field of extracellular vesicle (EV) biology, as well as cell biology, using advanced nanofabrication and nanoscopic fluid flows to advance understanding of EV heterogeneity and how phenotypic va ....Harnessing nanotechnology to unravel extracellular vesicle heterogeneity. This project aims to develop a suite of innovative nanotechnologies to study extracellular vesicles with unprecedented depth of analysis and single particle resolution. This project expects to generate new knowledge in the emerging field of extracellular vesicle (EV) biology, as well as cell biology, using advanced nanofabrication and nanoscopic fluid flows to advance understanding of EV heterogeneity and how phenotypic variations affect their role in cellular processes. Expected outcomes include a universal technology platform to study extracellular vesicles and other bioparticles, with potential to deliver valuable intellectual property of commercial interest and economic benefit through technological advancements.Read moreRead less
Enhancing aquaculture production of the tropical abalone using complementary genetic and environmental approaches. While temperate abalone are one of our most valuable seafoods, there is a growing demand worldwide for the ?cocktail?-sized tropical abalone Haliotis asinina. Australia is well positioned to capture the market for this rapidly growing species. We propose to enhance the already favourable growth rates of Haliotis asinina in aquaculture by delineating critical environmental and geneti ....Enhancing aquaculture production of the tropical abalone using complementary genetic and environmental approaches. While temperate abalone are one of our most valuable seafoods, there is a growing demand worldwide for the ?cocktail?-sized tropical abalone Haliotis asinina. Australia is well positioned to capture the market for this rapidly growing species. We propose to enhance the already favourable growth rates of Haliotis asinina in aquaculture by delineating critical environmental and genetic factors that effect production. This proposal uniquely melds commercial production practices at MG Kailis Export Pty Ltd with expertise in aquaculture and marine biotechnology present at The University of Queensland and CSIRO Marine Research. This knowledge will enhance the development of this new aquaculture industry in tropical Australia.Read moreRead less
Improving likelihood estimators: theory and applications to analysing productivity and efficiency and forecasting of probability of economic recession. This project aims to improve one of the most popular statistical methods to empower applied researchers with a more reliable analytical tool. This project will develop mathematical theory and use it to analyse patterns of economic growth, productivity and efficiency of countries. This can be used to forecast probability of entering economic reces ....Improving likelihood estimators: theory and applications to analysing productivity and efficiency and forecasting of probability of economic recession. This project aims to improve one of the most popular statistical methods to empower applied researchers with a more reliable analytical tool. This project will develop mathematical theory and use it to analyse patterns of economic growth, productivity and efficiency of countries. This can be used to forecast probability of entering economic recession, with a focus on Australia.Read moreRead less