Regulators Of G Protein Signalling On The Golgi Complex
Funder
National Health and Medical Research Council
Funding Amount
$666,116.00
Summary
The secretion of proteins from cells involves a host of regulatory and signalling proteins. G proteins, signal transducers, located on the Golgi membranes, participate in the budding of transport vesicles in the secretory pathway. A newly-discovered family of Regulators of G Protein Signalling (RGS) proteins perform the critical function of turning off signals generated by G proteins. RGS proteins are powerful, but as yet, ill-defined regulatory molecules. In this study we will identify and char ....The secretion of proteins from cells involves a host of regulatory and signalling proteins. G proteins, signal transducers, located on the Golgi membranes, participate in the budding of transport vesicles in the secretory pathway. A newly-discovered family of Regulators of G Protein Signalling (RGS) proteins perform the critical function of turning off signals generated by G proteins. RGS proteins are powerful, but as yet, ill-defined regulatory molecules. In this study we will identify and characterize RGS proteins in macrophages that are located on Golgi membranes and help to regulate cytokine secretion and other immune functions. More detailed studies on selected RGS proteins will include mutational analysis of functional domains within the proteins and identification of other proteins that interact with RGS proteins. Overall these studies will lead us to understand how specific RGS proteins interact with G proteins and other molecules to regulate signalling in the secretory pathway. Anomalies in cell signalling have severe consequences in a variety of diseases and can cause cancer. Similarly, abnormal secretion in cells contributes to inflammation, diabetes and other disease processes. Information forthcoming from our studies on RGS proteins will have wide-reaching implications and the potential to reveal new targets for therapeutics in these diseases.Read moreRead less
Molecular Mechanisms Underlying G Protein Coupled Receptor Signaling
Funder
National Health and Medical Research Council
Funding Amount
$596,956.00
Summary
The maintenance of optimum health and function of living cells, and consequently that of the whole organism, depends on how cells respond to a multitude of physical and chemical stimuli that continually bombard them. The majority of the chemical stimuli such as hormones and neurotransmitters impart their actions not by directly entering the cell, but instead, by binding to a specific receiver protein at the cell surface called a receptor. In one class of such receptors called G protein-coupled r ....The maintenance of optimum health and function of living cells, and consequently that of the whole organism, depends on how cells respond to a multitude of physical and chemical stimuli that continually bombard them. The majority of the chemical stimuli such as hormones and neurotransmitters impart their actions not by directly entering the cell, but instead, by binding to a specific receiver protein at the cell surface called a receptor. In one class of such receptors called G protein-coupled receptors, the transmission of the message to the interior of the cell involves yet another protein called G protein. These receptors are the most abundant type of cell surface receptors and form the targets for nearly 50% of currently used therapeutic drugs. It is, therefore, extremely important to unravel how each of these components works, and in particular to know how they work in living cells. This project utilizes state-of-the-art methodologies to examine interactions between receptors and their cognate G proteins, in living cells and in real-time. The work will answer fundamental questions about the nature of G protein-coupled receptor signaling and will aid in the future development of more effective therapeutic agents.Read moreRead less
Structural Characterisation Of SNARE Protein Complexes Involved In Insulin-regulated Glucose Transport
Funder
National Health and Medical Research Council
Funding Amount
$320,803.00
Summary
Insulin-regulated glucose transportation is defective in type 2 diabetes, a disease that is a major health problem worldwide and in some cases can lead to death. The aim of this work is to investigate the molecular structure and function of proteins critical to the transportation and delivery of glucose to muscle and fat cells, which will lead to the validation of new therapeutic targets and the development of new treatments for diabetes.