The PDZ Scaffold NHERF-1; A Novel Regulator Of Astrocyte Function?
Funder
National Health and Medical Research Council
Funding Amount
$444,500.00
Summary
Astrocytes are a vital cell type in the human brain. They provide nutrients to neurons, remove toxic chemicals such as glutamate (a neurotransmitter), as well as stabilising the levels of molecules such as water and ions such as sodium, bicarbonate and potassium. Astrocytes perform all these tasks by means of specialised protein molecules called transporters that are embedded in their cell membranes. These transporters are not uniformly distributed; they are positioned in those parts of the astr ....Astrocytes are a vital cell type in the human brain. They provide nutrients to neurons, remove toxic chemicals such as glutamate (a neurotransmitter), as well as stabilising the levels of molecules such as water and ions such as sodium, bicarbonate and potassium. Astrocytes perform all these tasks by means of specialised protein molecules called transporters that are embedded in their cell membranes. These transporters are not uniformly distributed; they are positioned in those parts of the astrocyte membranes where the particular biological job has to be performed. How are they targeted to, and retained in these places? We have preliminary data suggesting that a specialised protein called NHERF-1, can bind a group of these proteins, called glutamate transporters, thereby anchoring them to the skeleton of the cell. If we are correct then we should be able to manipulate this interaction, both in live brain tissues, and in simple cell culture systems, using a variety of physiological and molecular biology techniques. If we are correct in our hypothesis, then our findings will have immense value in trying to reduce damage that occurs in human brains in conditions such as strokes, where a breakdown in the control of glutamate around neurons causes extensive and irreversible brain damage.Read moreRead less
Characterisation Of A Novel Direct Electrochemical Chip As A Biosensor And Tool For Studying Redox-sensitive Proteins
Funder
National Health and Medical Research Council
Funding Amount
$144,500.00
Summary
Biosensors use biomolecules to detect a chemical event. They are becoming important for the rapid and reliable measurement of the concentrations of molecules in fluids. In human medicine they will be of great use to general practitioners and patients for instantaneous read outs of concentrations of many different biological molecules. How well a biosensor responds depends on the method in which the biomolecule is immobilised to a surface and the signal detected. We have made a significant advanc ....Biosensors use biomolecules to detect a chemical event. They are becoming important for the rapid and reliable measurement of the concentrations of molecules in fluids. In human medicine they will be of great use to general practitioners and patients for instantaneous read outs of concentrations of many different biological molecules. How well a biosensor responds depends on the method in which the biomolecule is immobilised to a surface and the signal detected. We have made a significant advance in biosensing capabilities using a recombinant protein (thioredoxin) and demonstrated the improvement that is possible by (i) immobilising the protein in a highly oriented way and (ii) using a sensitive electrical signal to monitor the response. Here we will undertake more comprehensive testing by extending the number of proteins to include the 4 major classes of redox-sensitive biomolecules (proteins) in the body. This will enable us to establish the broad application of our methods and substantially improve our ability to commercialize our discoveries.Read moreRead less