The rapid emergence and spread of antibiotic resistance in bacteria that cause infectious diseases is of major concern to public health authorities throughout the world. Many of the genes that are responsible for this resistance are carried on mobile genetic elements, which are discrete segments of genetic material that can move from one bacterium to another. These genetic elements are important vehicles for the transmission of virulence and antibiotic resistance genes in most bacteria. This pro ....The rapid emergence and spread of antibiotic resistance in bacteria that cause infectious diseases is of major concern to public health authorities throughout the world. Many of the genes that are responsible for this resistance are carried on mobile genetic elements, which are discrete segments of genetic material that can move from one bacterium to another. These genetic elements are important vehicles for the transmission of virulence and antibiotic resistance genes in most bacteria. This project is centred on bacteria that cause intestinal diseases and have the potential to transfer genetic information to other bacteria that are present in the intestine. The focus will be on elucidating the mechanism of action of an enzyme encoded by two of these genetic elements. This enzyme is responsible for the movement of these elements from one site in the bacterial genome to another, by a process that is being increasingly recognised as important in antibiotic-resistant disease-causing bacteria. The project will employ the latest tools of molecular biology to determine the function of this enzyme, and its associated genetic elements, at the detailed molecular level. These studies will contribute to our understanding of how these antibiotic resistance elements are transferred within and between different bacterial cells. In the longer term the project will contribute towards the development of improved methods for the control and treatment of infectious diseases.Read moreRead less
Gene targeting in the rat germ cell. The rat plays a central role in both medical research and the drug development process. Unfortunately key technologies supporting the genetic modification of the rat are currently unavailable. The development of such technology would dramatically improve the utility of the rat in many areas of medical research as well as for the pharmaceutical industry. This project proposes to develop methods to perform gene targeting experiments in the germ cells of the ....Gene targeting in the rat germ cell. The rat plays a central role in both medical research and the drug development process. Unfortunately key technologies supporting the genetic modification of the rat are currently unavailable. The development of such technology would dramatically improve the utility of the rat in many areas of medical research as well as for the pharmaceutical industry. This project proposes to develop methods to perform gene targeting experiments in the germ cells of the male rat. Successful manipulation of these cells will represent a major breakthrough towards the ultimate goal of manipulating the rat genome.Read moreRead less
How does clusterin protect cells from stresses? We recently discovered that clusterin: (i) is the only known secreted (ie extracellular) mammalian chaperone and (ii) can protect proteins and cells from stresses.These breakthrough advances provide the first unifying biological function for this protein - in whole organisms, clusterine is likely to protect tissues and organs form biologyical stresses. The work proposed will provide quantum advances in our understanding of the molecular basis by wh ....How does clusterin protect cells from stresses? We recently discovered that clusterin: (i) is the only known secreted (ie extracellular) mammalian chaperone and (ii) can protect proteins and cells from stresses.These breakthrough advances provide the first unifying biological function for this protein - in whole organisms, clusterine is likely to protect tissues and organs form biologyical stresses. The work proposed will provide quantum advances in our understanding of the molecular basis by which clusterin effects its protective actions. We expect to demonstrate that clusterin protects cells form stresses by exerting its chaperone action at or near the cell surface and to identify specific regions and structural features of the clusterine molecule important in its chaperone action.Read moreRead less
MOLECULAR STRUCTURE-FUNCTION RELATIONSHIPS OF THE NORADRENALINE TRANSPORTER & DRUG ACTION
Funder
National Health and Medical Research Council
Funding Amount
$188,912.00
Summary
The transmission of impulses by nerves is dependent on the release of chemicals, termed neurotransmitters, from the nerve. The neurotransmitter causes its effects and then its action is usually terminated by membrane proteins that transport the chemical back into the nerve. These proteins are termed 'transporters'. In the brain, psychostimulants such as cocaine and also drugs that are used in the therapy of conditions such as depression block the activity of the transporters for the neurotransmi ....The transmission of impulses by nerves is dependent on the release of chemicals, termed neurotransmitters, from the nerve. The neurotransmitter causes its effects and then its action is usually terminated by membrane proteins that transport the chemical back into the nerve. These proteins are termed 'transporters'. In the brain, psychostimulants such as cocaine and also drugs that are used in the therapy of conditions such as depression block the activity of the transporters for the neurotransmitters, noradrenaline, serotonin and dopamine. Recently, the structures of the transporter proteins have been determined using molecular biology techniques. The focus of this project is to determine the parts of the noradrenaline transporter protein structure that are important in determining its functions, utilising the knowledge that we now have about its molecular structure. This will lead to exciting advances in understanding the function of the noradrenaline transporter and these advances should ultimately lead to the development of more effective antidepressant drugs and of drugs to prevent the effects of psychostimulants such as cocaine.Read moreRead less