A DENDRITIC SUBSTRATE FOR THE CHOLINERGIC CONTROL OF NEOCORTICAL OUTPUT
Funder
National Health and Medical Research Council
Funding Amount
$898,340.00
Summary
The forebrain cholinergic system controls neocortical activity and cognitive function. This project will investigate the mechanisms by which the cholinergic system controls neocortical circuit activity in rodent models using advanced optical and electrical recording methods. The results will provide a foundation for the understanding of how dysfunction of the cholinergic system results in cognitive decline in humans, and identify new targets for improved treatment of human cognitive impairment.
Regulation Of Synaptic Vesicle Biogenesis For Synaptic Transmission
Funder
National Health and Medical Research Council
Funding Amount
$339,115.00
Summary
The overall aim is to better understand the molecular processes of nerve cell communication during learning, memory and abnormal brain activity that cause neurological diseases. The supply and generation (biogenesis) of synaptic vesicles (SVs) in nerve cells is critical to sustain neurotransmission. It requires complex protein interactions and signalling. Thus modulation of SV biogenesis at the molecular level will allows future development of new targeted treatments for neurological diseases.
Investigation Of The Molecular Mechanisms Underlying Alpha Synuclein Function At The Presynapse
Funder
National Health and Medical Research Council
Funding Amount
$419,180.00
Summary
Parkinson’s Disease (PD) is a common brain disease affecting 7 million people worldwide. It is caused by the death of brain cells. ?-synuclein is a protein in that brain that is likely to contribute to the cell death in PD, but the normal role of the protein remains unknown. This study will investigate the function of ?-synuclein in maintaining normal healthy brain activity. In addition, this work will help us understand how normal brain processes are affected in diseases such as PD.
Investigation Of Molecular And Cellular Determinants Of Immune Related Adverse Events Following Treatment With Immune Checkpoint Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Novel immune-based treatments for advanced, incurable, cancer have significantly improved patient survival. Although these treatments have proven highly effective, they are associated with the unpredictable development of severe and sometimes life-threatening autoimmune disease. We aim to discover ways to predict and potentially prevent these complications by identifying genetic risk factors and markers in blood samples. If successful, this will be a ground breaking advance in cancer care.
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
Synaptic Integration And Plasticity In The Rat Piriform Cortex
Funder
National Health and Medical Research Council
Funding Amount
$250,500.00
Summary
The human cerebral cortex is the pinnacle of evolution. It is the most complex structure known, responsible for all of those skills - like language and reasoning - that make our species so remarkable. It is also a major site of many brain diseases, like schizophrenia and epilepsy. An understanding of how the cerebral cortex works would be a remarkable achievement, of immeasurable benefit to human health. How can one go about studying such a complex structure? The strategy taken in this project i ....The human cerebral cortex is the pinnacle of evolution. It is the most complex structure known, responsible for all of those skills - like language and reasoning - that make our species so remarkable. It is also a major site of many brain diseases, like schizophrenia and epilepsy. An understanding of how the cerebral cortex works would be a remarkable achievement, of immeasurable benefit to human health. How can one go about studying such a complex structure? The strategy taken in this project is to begin by studying one of the simplest regions of the cerebral cortex, the olfactory (or piriform) cortex. The olfactory cortex is an evolutionarily ancient region of cortex, with a simpler architecture than other cortical regions. Its task is to process the sense of smell, a primitive sense that is more elaborated in lower animals than in humans. The broad goal of our research is to understand, by studying the olfactory cortex of rats, how olfactory processing occurs at the level of nerve cells (neurons). We will use a number of powerful techniques - including microelectrode recording and laser microscopy - to measure the electrical properties of individual neurons. We will also study the synaptic connections between neurons, and how these connections change following memory-inducing stimuli. It is hoped that this work will shed light on how the healthy cortex is able to process and store information, and how brain diseases cause these functions to deteriorate.Read moreRead less
Exploiting And Defining The Immune Regulatory Activities Of BET Bromodomain Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Immune-based agents such as “checkpoint inhibitors” have the ability to re-awaken our own immune systems and activate previously dormant anti-tumour responses. We have discovered that small molecule inhibitors of gene regulatory proteins called bromodomain proteins act synergistically with checkpoint inhibitors in mouse cancer models. I will define the molecular and biological events underpinning this novel combination approach and assess the effects of the combination across different tumours.
Antibiotic Conjugates: Joining Together To Fight Antimicrobial Resistance
Funder
National Health and Medical Research Council
Funding Amount
$697,675.00
Summary
New strategies are urgently needed to treat the rise of infections from multidrug-resistant bacteria, with standard antibiotic therapies becoming obsolete. This project will develop multiple innovative approaches to overcome antibiotic resistance, based on a core concept of appending additional functionality to existing antibiotic scaffolds. New conjugates will be synthesized, tested for antimicrobial activity, then optimized via a validated antimicrobial development pipeline.