Compared with normal-weight children, obese youth have a higher chance of developing diseases like Type 2 diabetes. With 1 in 4 Australian children now being overweight or obese, effective treatment programs need to be developed alongside those aimed at prevention. This program of research aims to identify which overweight/obese children are most likely to develop diabetes, with a particular focus on how infant nutrition regulates important growth factors to alter long-term diabetes risk.
IGF BINDING PROTEIN-2 A MODULATOR OF IGF ACTION IN DEVELOPING AND NEOPLASTIC NEURONAL CELLS.
Funder
National Health and Medical Research Council
Funding Amount
$436,980.00
Summary
In early life the brain undergoes rapid growth and remodelling, a process regulated by many factors including the insulin-like growth factor (IGF) system, which potently enhances nerve cell (neuron) survival. Similarly, this system is active in response to brain injury such a stroke, but it may also enhance tumor survival. The regulation of availability of IGFs to the neuron is critical in all these processes. IGF binding protein-2 (IGFBP-2), which is highly abundant in the developing or damaged ....In early life the brain undergoes rapid growth and remodelling, a process regulated by many factors including the insulin-like growth factor (IGF) system, which potently enhances nerve cell (neuron) survival. Similarly, this system is active in response to brain injury such a stroke, but it may also enhance tumor survival. The regulation of availability of IGFs to the neuron is critical in all these processes. IGF binding protein-2 (IGFBP-2), which is highly abundant in the developing or damaged brain, and in tumours, plays a key role on the surface of neurons in regulating IGF availability. We have shown that IGFBP-2 associates with a specialised protein on the nerve cells, where it is further processed to smaller fragments. We believe that these processes are reactivated following brain injury or in cancer states where IGFBP-2 is highly abundant. We propose to determine how IGFBP-2 influences IGF action on the nerve cell surface, and to further ascertain the function of each step in this process. We will achieve this by examining the effects of the mutated version of IGFBP-2, designed to either prevent its binding to the cell surface or its processing to smaller fragments. We will use various human and mouse nerve cell for these studies, which will not only provide greater understanding of the regulation of IGF availability to developing brain cell, but also point to how these processes may be involved in enhancement of recovery from injury or stroke, or possibly in acceleration of tumour growth. The finding of this study will offer the potential for new and exciting treatment designed to alter the function of the IGF system, to either make it more active in response to brain injury or stroke, or less active in brain tumours.Read moreRead less
Insulin-like Growth Factor Binding Protein-2 Is A Crucial Activator Of Aggressive Behaviour In Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$612,885.00
Summary
The insulin-like growth factor (IGF) system, required for normal development and adult life, is often altered in many diseases including cancer. Key regulators of the IGF system are the IGF binding protein (IGFBP) of which IGFBP-2 is the 2nd most abundant. IGFBP-2 may enhance or inhibit the IGFs, but the mechanisms are not clear. This proposal aims to dissect IGFBP-2 action with the ultimate goal to provide knowledge for the development of targeted therapeutic modulators of IGFBP-2 activity.
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