Analysis Of Intracellular Signalling And Biological Activities Of The GM-CSF Receptor Family Using Constitutive Mutants
Funder
National Health and Medical Research Council
Funding Amount
$505,699.00
Summary
The cytokines GM-CSF, IL-3 and IL-5 stimulate the growth and actions of a wide range of blood cells. Each binds to a receptor on the cell surface which then triggers the generation of a number of signals inside the cell; it is these signals that are responsible for the cytokine?s actions. We have previously generated a panel of constitutive mutant forms of the beta subunit which is shared by the GM-CSF, IL-3 and IL-5 receptors. These constitutive mutants trigger signals even in the absence of th ....The cytokines GM-CSF, IL-3 and IL-5 stimulate the growth and actions of a wide range of blood cells. Each binds to a receptor on the cell surface which then triggers the generation of a number of signals inside the cell; it is these signals that are responsible for the cytokine?s actions. We have previously generated a panel of constitutive mutant forms of the beta subunit which is shared by the GM-CSF, IL-3 and IL-5 receptors. These constitutive mutants trigger signals even in the absence of the cytokine; importantly, the different mutants appear to trigger only a subset of the signals generated by the normal receptor. The aim of this project is to use our panel of constitutive beta subunit mutants to determine how the GM-CSF, IL-3 and IL-5 receptors generate signals inside the cell and how these signals lead to the various biological actions of the receptors on blood cell growth and maturation. Findings from this research will be relevant to the understanding and treatment of diseases which involve abnormal growth or function of blood cells such as leukaemia and inflammatory diseases.Read moreRead less
Sorting Nexins And Their Role In Endosomal Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$331,000.00
Summary
Cells are able to internalise molecules via membrane-bound vesicles, a process known as endocytosis. Endocytosis is fundamental for many cellular processes, including receptor signalling, uptake of many essential nutrients and the ability to mount an effective lymphocyte response to foreign antigens. Once internalised, cargo is then sorted to different intracellular destinations of the endosomal transport system. The ultimate destination depends on the particular cargo molecule. The importance o ....Cells are able to internalise molecules via membrane-bound vesicles, a process known as endocytosis. Endocytosis is fundamental for many cellular processes, including receptor signalling, uptake of many essential nutrients and the ability to mount an effective lymphocyte response to foreign antigens. Once internalised, cargo is then sorted to different intracellular destinations of the endosomal transport system. The ultimate destination depends on the particular cargo molecule. The importance of the endosomal transport system is also highlighted by the discovery that many human diseases, including various cancers, lysosomal storage diseases and hypercholesterolemia, are linked to defects in trafficking along the endocytic pathway. Furthermore, a number of viral pathogens, such as HIV, and toxins, such as shiga toxin, exploit the endosomal system to gain entry into a cell. Understanding the molecular details of the sorting events within the endosomal system is necessary to be able to consider therapeutic manipulation of the trafficking of specific cargo molecules. The study seeks to understand the molecular details of the endosomal sorting machinery, knowledge that will underpin future efforts to develop drugs to manipulate movement of proteins within the endosomal system. In the long term, this could allow for the manipulation of a variety of cellular functions including the inhibition of proliferative signals in tumour cells.Read moreRead less