Substances that enhance the action of the inhibitory neurotransmitter GABA in the brain are amongst the most widely used drugs. They include many anaesthetics, anxiolytics and sedatives. Their enhancing action is mediated by increasing the effectiveness of GABA acting on GABA receptors, in particular the subtype of GABA receptors known as GABA-A receptors. This action, termed positive modulation, is poorly understood in molecular terms. Our discovery of second order modulators that only act in c ....Substances that enhance the action of the inhibitory neurotransmitter GABA in the brain are amongst the most widely used drugs. They include many anaesthetics, anxiolytics and sedatives. Their enhancing action is mediated by increasing the effectiveness of GABA acting on GABA receptors, in particular the subtype of GABA receptors known as GABA-A receptors. This action, termed positive modulation, is poorly understood in molecular terms. Our discovery of second order modulators that only act in conjunction with first order modulators adds an exciting new dimension to the concept of influencing the ways in which GABA receptors can be modulated. This offers a new approach to the development of therapeutic agents acting on GABA receptors and thus the treatement of important disorders such as anxiety, epilepsy and insomnia.Read moreRead less
Cellular Microenvironments Facilitating The Replication And Propagation Of Flaviviruses
Funder
National Health and Medical Research Council
Funding Amount
$505,279.00
Summary
Flaviviruses are the agents of many mosquito-transmitted infections and many deaths globally each year. The emerging virus West Nile virus (strain New York) is a member of this virus family and shares 99% amino acid homology with the endemic Australian virus Kunjin virus. During virus growth in cells, cellular membrane structures are induced or rearranged by these viruses for their own purpose. That being the production of more virus particles for reinfection of other cells. Using Kunjin virus a ....Flaviviruses are the agents of many mosquito-transmitted infections and many deaths globally each year. The emerging virus West Nile virus (strain New York) is a member of this virus family and shares 99% amino acid homology with the endemic Australian virus Kunjin virus. During virus growth in cells, cellular membrane structures are induced or rearranged by these viruses for their own purpose. That being the production of more virus particles for reinfection of other cells. Using Kunjin virus as a model, and advanced techniques in biochemistry and electron microscopy, we have identified for the first time these membrane structures as the apparent sites of replication of the viral RNA or genetic material, and of the viral proteins involved. We have also observed how new virus particles are able to get out of infected cells and shown how some drugs can prevent this occurring thus limiting their transmission. This research will focus on how the membrane structures are formed in infected cells. The research will determine what cellular components are required by the virus to help it propagate. In particular specific cellular proteins and membrane components that are captured by the virus and moved to different sites in the infected cells. These apparent requirements could possibly lead us to a greater understanding of the complex interactions that occur between the invading virus and the host cells. We aim to directly visualize the process of infection within living cells using new and innovative microscopic techniques. Another of our objectives is to determine the effects of infection on normal cells. The question being whether flavivirus infection disrupts normalcell fuctions like secretion etc. An understanding of these processes, and how the viral RNA is copied into new RNA for more virus particles, will assist in the development of antiviral drugs for treatment of this pathogenic group of viruses.Read moreRead less