Structure, Transport And Assembly Of PorB, A Key Invasion Molecule Of Meningococcal Disease
Funder
National Health and Medical Research Council
Funding Amount
$292,639.00
Summary
When the bacteria that cause meningococcal disease invade cells, they use specialized cell surface pore proteins to hijack the human cell and maintain infection. This research will study the structure of these bacterial pore proteins to help understand how they function to subvert normal cellular processes, and this insight will be important in the development of new treatments for meningococcal disease.
Prof Parton is a cell biologist studying how the plasma membrane functions in health and in disease. These studies have provided new insights into potential vehicles that can be used to introduce therapeutic agents into cells.
The Role Of Plasma Membrane Microdomains In Cellualar Function
Funder
National Health and Medical Research Council
Funding Amount
$4,083,868.00
Summary
The planned research program relates to novel hypotheses regarding the role of cell surface domains in organising signalling pathways at the cell surface. The proposal will involve identifying the domains and molecules involved in specific signalling pathways and dissecting the formation and function of surface structures called caveolae. The findings will have huge importance for therapeutic strategies aimed at combating the cellular changes associated with cell transformation in cancer and oth ....The planned research program relates to novel hypotheses regarding the role of cell surface domains in organising signalling pathways at the cell surface. The proposal will involve identifying the domains and molecules involved in specific signalling pathways and dissecting the formation and function of surface structures called caveolae. The findings will have huge importance for therapeutic strategies aimed at combating the cellular changes associated with cell transformation in cancer and other human diseases.Read moreRead less
Functional Characterization Of Caveolae And Caveolins
Funder
National Health and Medical Research Council
Funding Amount
$140,660.00
Summary
This project aims to study the cellular machinery that allows a cell to respond to its external environment. Specifically, this project focusses on the function of a family of membrane proteins, called caveolins, which are the major protein components of caveolae small pits which cover the surface of many mammalian cells. Caveolins are believed to regulate signalling from the external environment to the cell interior and loss of this regulation leads to uncontrolled growth leading to cancer. Sig ....This project aims to study the cellular machinery that allows a cell to respond to its external environment. Specifically, this project focusses on the function of a family of membrane proteins, called caveolins, which are the major protein components of caveolae small pits which cover the surface of many mammalian cells. Caveolins are believed to regulate signalling from the external environment to the cell interior and loss of this regulation leads to uncontrolled growth leading to cancer. Signalling from the cell surface relies on organisation of signalling components into modules. Our studies suggest that these modules are dependent on specific lipid molecules which form discrete patches, called lipid rafts, on the cell surface. We have hypothesised that caveolins control the lipid molecules associated with lipid rafts and so, indirectly, control signalling pathways. In particular, we have shown that caveolin is important in the regulation of cellular cholesterol, a vital molecule involved in maintaining the function of lipid raft domains. As numerous human diseases are associated with cholesterol imbalance, studies of caveolins can give fundamental new insights into this process, and the previously unidentified links between the cellular lipid balance and signal transduction. This project aims to use mutant caveolin molecules to disrupt caveolin function and so determine the role of caveolin in lipid regulation and in signal transduction. We will then use a lower vertebrate model system, which is amenable to experimental manipulation, to determine the role of caveolins and rafts in the development of the whole embryo.Read moreRead less
The Regulation Of PI 3-kinase Second Messenger Molecules, PtdIns(3,4)P2 And PtdIns 3-P.
Funder
National Health and Medical Research Council
Funding Amount
$406,980.00
Summary
Cells respond to the external environment, hormones, and growth factors by generating messages inside the cell that send a signal to the nucleus that stimulates cell growth. One such signalling network is that produced by membrane lipids known as phosphoinositides. Enzymes that produce these signals are known as kinases. There has been considerable interest in the PI 3-kinase as the signals generated by this enzyme are increased in many human cancers. Inherited cancer syndromes have been describ ....Cells respond to the external environment, hormones, and growth factors by generating messages inside the cell that send a signal to the nucleus that stimulates cell growth. One such signalling network is that produced by membrane lipids known as phosphoinositides. Enzymes that produce these signals are known as kinases. There has been considerable interest in the PI 3-kinase as the signals generated by this enzyme are increased in many human cancers. Inherited cancer syndromes have been described that have lost the ability to switch off PI 3-kinase signals. The current project aims to investigate a recently identified enzyme called the 4-phosphatase that has the ability to terminate PI 3-kinase signals. Recent studies have shown this enzyme regulates cell growth. In addition key experiments have shown the enzyme is important as it may regulate certain strains of bacterial infection. This research proposal aims to investigate how the enzyme works to regulate these growth promoting signals. This may help us develop novel therapeutic strategies to control cell growth.Read moreRead less
Structural Studies Of The Jak And Abl Kinases: A Prerequisite For Drug Design
Funder
National Health and Medical Research Council
Funding Amount
$360,965.00
Summary
Protein tyrosine kinases (PTK) are a large, pivotal family of signalling molecules implicated in diseases such as cancer and immune related disorders. This fellowship aims to develop more potent kinase inhibitors of a number of PTKs using Cytopia’s drug discovery capability coupled with the X-ray crystallography expertise within Monash University. This innovative approach will permit a rational structure-based drug discovery platform to be established and will lead to the creation of a portfolio ....Protein tyrosine kinases (PTK) are a large, pivotal family of signalling molecules implicated in diseases such as cancer and immune related disorders. This fellowship aims to develop more potent kinase inhibitors of a number of PTKs using Cytopia’s drug discovery capability coupled with the X-ray crystallography expertise within Monash University. This innovative approach will permit a rational structure-based drug discovery platform to be established and will lead to the creation of a portfolio of phase I therapeutics, which will be of substantial benefit in the medical health area.Read moreRead less
Molecular And Functional Characterisation Of Cell Surface Microdomains
Funder
National Health and Medical Research Council
Funding Amount
$4,803,731.00
Summary
This research program aims to gain a detailed understanding of the organisation of the cell surface at the molecular level. The cell surface is organised into domains with distinct functions. Visualisation of these domains, identifying their important components, and understanding how they form and function will have huge importance for therapeutic strategies aimed at combating the changes associated with cell transformation in cancer and in other human diseases such as muscular dystrophy.