The Interplay Between Viperin, Peroxisomes And The Cellular Innate Antiviral Response
Funder
National Health and Medical Research Council
Funding Amount
$556,127.00
Summary
Infection with a virus initiates a cellular antiviral response that attempts to limit viral replication, however how this response is regulated is not well understood. In this proposal we will investigate a cellular protein (viperin) that can regulate this process by interaction with peroxisomes to amplify the antiviral response. This work will provide possible targets for therapeutic manipulation of the innate immune response that will be applicable to a wide range of viral infections.
Imaging The Hepatitis C Virus Life Cycle In Real-time
Funder
National Health and Medical Research Council
Funding Amount
$477,504.00
Summary
Hepatitis C virus (HCV) is a serious viral pathogen that causes significant liver disease. This proposal plans to examine how two proteins from the HCV, core and NS5A, interact with host proteins and pathways to facilitate viral replication and release of HCV; two processes that are poorly understood. Specifically we will tag viral proteins to allow us to investigate the HCV life cycle in living cells and determine the role of core and NS5A in facilitating HCV replication. This proposal may unco ....Hepatitis C virus (HCV) is a serious viral pathogen that causes significant liver disease. This proposal plans to examine how two proteins from the HCV, core and NS5A, interact with host proteins and pathways to facilitate viral replication and release of HCV; two processes that are poorly understood. Specifically we will tag viral proteins to allow us to investigate the HCV life cycle in living cells and determine the role of core and NS5A in facilitating HCV replication. This proposal may uncover novel therapeutic strategies to combat HCV.Read moreRead less
Neuronal Substrate Of Choice In The Rat Whisker System
Funder
National Health and Medical Research Council
Funding Amount
$405,851.00
Summary
Humans and other animals can optimise their goal-directed behaviour by linking stimuli or actions to consequent positive and negative rewards. How does an animal generate such associations, and make decisions in the natural environment where the associations are often uncertain, at times contradictory, and continuously changing? This project uses rat whisker system as an animal model to identify the neuronal basis of perceptual decision making and the role of context.
Assembly And Transport Of Herpes Simplex Virus Within Neurones
Funder
National Health and Medical Research Council
Funding Amount
$475,500.00
Summary
Herpes simplex virus (HSV) enters the human body via the skin before entering the termini of nerve cell processes. It is transported along these processes to the body of the nerve cell. HSV lies dormant within these nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported back down the nerve cell processes to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how HSV is transpor ....Herpes simplex virus (HSV) enters the human body via the skin before entering the termini of nerve cell processes. It is transported along these processes to the body of the nerve cell. HSV lies dormant within these nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported back down the nerve cell processes to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how HSV is transported and assemblied within nerve cells at the molecular level. Recent discoveries have shown how virus transport in nerve cells is dependent on interactions between specific viral proteins and cellular motor proteins. Such information on viral transport and assembly mechanisms will allow development of inhibitors of these processes which may be candidates for use as antivirals for control of recurrent herpes simplex. In addition, this information will allow the virus to be exploited for use in gene therapy to introduce DNA into human nerve cells to correct genetic abnormalities.Read moreRead less
Transport, Assembly And Egress Of Herpes Simplex Virus In Neurones
Funder
National Health and Medical Research Council
Funding Amount
$639,661.00
Summary
Herpes simplex viruses 1 and 2 are important pathogens, causing encephalitis, blindness and severe neonatal infection but they also enhance the acquisition of HIV three-fold. The transport of the virus to and from the periphery to the spinal cord is a key component of their life cycle. Determination of the exact mechanism will assist in a general understanding of nerve function and the development of new strategies for antiviral drugs.
THE EFFECT OF STRESS AND ENVIRONMENTAL ENRICHMENT ON DISEASE PROGRESSION IN MESIAL TEMPORAL LOBE EPILEPSY
Funder
National Health and Medical Research Council
Funding Amount
$578,201.00
Summary
Mesial temporal lobe epilepsy, the most common form of drug-resistant epilepsy in adults, is a progressive neurodegenerative condition for which there is currently no effective disease modifying treatment. This proposal will explore whether co-morbid stress accelerates disease progression in MTLE, and whether targeting stress pathways by medical and environmental manipulations can mitigate against this.
A Multi-national Trial To Predict Treatment Response In Subtypes Of Depression
Funder
National Health and Medical Research Council
Funding Amount
$387,489.00
Summary
Treatment of MDD using trial and error can have serious consequences. It can prolong the patient’s suffering (depression is associated with substantial morbidity, and mortality), prolong their absence from work and other productive activity and increase the burden on their family-carers. This multi-national study will collect genetics, brain function and behavioural data from a large number of participants, allowing for sensitive predictors of response to be determined.
Predictors Of Response To Antidepressants: Utility Of Behavioural, Neuroimaging And Genetics Data
Funder
National Health and Medical Research Council
Funding Amount
$310,071.00
Summary
Major depressive disorder (MDD) is projected to cause the second greatest global burden of disease by 2020, highlighting the urgent need for valid predictors of effective treatment response. Currently, there are no accurate predictors of response to antidepressants in MDD, and successful treatment relies greatly on 'trial and error'. This process is demanding on health resources, and may be a factor in the high suicide rates in depressed patients. Previous research on treatment response has been ....Major depressive disorder (MDD) is projected to cause the second greatest global burden of disease by 2020, highlighting the urgent need for valid predictors of effective treatment response. Currently, there are no accurate predictors of response to antidepressants in MDD, and successful treatment relies greatly on 'trial and error'. This process is demanding on health resources, and may be a factor in the high suicide rates in depressed patients. Previous research on treatment response has been limited by recruitment of small, heterogeneous patient samples, lack of placebo control, and a failure to examine task related activity in brain imaging studies. Perhaps one of the more troubling aspects of research that aims to predict treatment response to antidepressant medications is the use of commonly used outcome measures such as the Hamilton Rating Depression Scale (HAM-D), which were developed long before current classification systems of depression came into use. The US Federal Drug Administration has recently identified what they call a translational gap such that behavioural and biological measures are the most robust for detection of disorders such as depression, yet these measures remain to be translated into clinical tools that can be used to evaluate treatment. The aim of the current study therefore is to determine whether genetic variability is related to treatment outcome as defined by a more objective outcome measure (facial expression perception) using a randomised controlled design. The study will also determine whether brain measures (fMRI, EEG) enhance the prediction of SSRI response to both clinical and behavioural measures, over and above the genetic contribution.Read moreRead less
The Role Of Corticothalamic Feedback On The Response Dynamics Of Thalamic Neurons
Funder
National Health and Medical Research Council
Funding Amount
$351,852.00
Summary
A fundamental question in neuroscience is how the brain selectively processes sensory information to generate a reliable representation of the world. Positioned in the centre of the brain, the thalamus plays a key role in sensory processing. This project investigates how the interaction between thalamus and cortex shapes the selection and gating of sensory information. This is a fundamental question in basic neuroscience with the potential to increase our knowledge about attentional deficits.