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.
Multi-centre, Multi-disciplinary Study Using A Systems Biology Approach To Investigate Immunomodulation In Children With Acute Wheeze
Funder
National Health and Medical Research Council
Funding Amount
$1,895,107.00
Summary
The concept that immunomodulation using naturally-occurring bacterial agents can treat asthma has reached international prominence. This is backed by strong epidemiologic and clinical trial data. However, detailed knowledge of the immunological mechanisms involved is essential to allow more focused therapeutic agents to be developed. The proposed multi-disciplinary immunomodulation study in 200 children aims to provide this essential information using an advanced systems biology approach.
The Differential Contribution Of Programmed Death-1 Ligands To Malarial Immunity
Funder
National Health and Medical Research Council
Funding Amount
$327,784.00
Summary
This research aims to understand how the Malaria parasite, which causes one of the world’s deadliest diseases, evades immunity. It will provide a significant advance in our knowledge of immunity against malaria and impact on current strategies to develop an efficacious vaccine or treatment for malaria.
Impact Of Somatic Versus Dendritic Inhibition On Neuronal Output
Funder
National Health and Medical Research Council
Funding Amount
$1,047,686.00
Summary
The brain is made up of literally billions of neurons connected in complex networks. These neurons come in two primary flavors - excitatory and inhibitory - which work in balance. Too much excitation and the brain becomes epileptic, too much inhibitory and we go into a coma. This proposal focuses on the role of specific inhibitory cell types in regulating brain function, and has relevant to a range of neurological disorders from epilepsy, to schizophrenia to depression.
Molecular Basis For The Efficient Processing Of Antigens Taken Up By Clec9A, A DAMP Receptor On Dendritic Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,302,392.00
Summary
Dendritic cells (DC) of the immune system utilise specific receptors to sense danger signals from their environment. We identified a DC danger receptor, Clec9A, which recognizes and induces immunity to “dangerous” dead cells eg. infected cells or killed tumour cells. We will investigate how DC use Clec9A to process “dangerous” dead cells, and the factors that control the potency of this immune response. This will enable us to develop novel immunotherapies for infectious diseases and cancer.
Role Of Dendritic Information Processing In Visual Circuit Computations
Funder
National Health and Medical Research Council
Funding Amount
$895,244.00
Summary
Vision is the primary sensory modality in man, and its disturbance carries an enormous socio-economic burden. The dynamic operations of the neuronal assemblies that underlie vision are poorly understood, partly because of an incomplete description of the computational properties of visual neuronal circuits. The aims of the application are to mechanistically dissect defined computational operations of visual neural circuits using advanced electrophysiological and optical recording techniques.
Cognitive Inflexibility And The Development Of Pathological Habits In Brain Diseases
Funder
National Health and Medical Research Council
Funding Amount
$883,946.00
Summary
Pathological habits are observed in severe mental health conditions including dementia, obsessive-compulsive disorder (OCD), schizophrenia, depression and addiction. This application aims to provide the mechanistic detail required for therapeutic targeting to restore flexible decision making in these conditions.
Role Of Calcium-activated Potassium Channels In Neuronal Excitability, Synaptic Plasticity And Sensory Processing
Funder
National Health and Medical Research Council
Funding Amount
$612,272.00
Summary
Disturbances in brain function, as occur in diseases such as epilepsy and schizophrenia, are associated with abnormal electrical activity. This electrical activity leads to increases in calcium inside nerve cells. In this project we plan to investigate how changes in calcium inside nerve cells regulates electrical activity, and how this impacts on the capacity of the brain to process and learn new information.
The Role Of Cytokines In Tumor-induced Immunosuppression
Funder
National Health and Medical Research Council
Funding Amount
$754,473.00
Summary
Cancer-induced immune suppression is a major obstacle to the effective treatment of many cancers. We have shown that the cytokine IL-23, plays an important role in cancer initiation, growth and development. My project aims to characterize the cells that produce IL-23 in the cancer microenvironment and define how it suppresses cells of the immune system. A greater understanding of this cytokine’s mechanism of action will enable the rational improvement of treatments for patients with cancer
Targeting The Synaptic Actin Cytoskeleton In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$840,741.00
Summary
Dementias have become one of the fastest growing sources of major disease burdens in developed countries with about one in fifteen Australians older than 65 being affected. We will study how pathological stimuli disrupt nerve cell connections in the brain by impacting on the cellular architecture at these connections. Findings from our study will provide profound new insights in how nerve cells communicate with each other and how this communication is breaking down in disease.