Currents That Set The Excitability Of Enteric Neurons And Their Roles At Cell And Organ Levels
Funder
National Health and Medical Research Council
Funding Amount
$459,014.00
Summary
The intestine is subject to a number of disorders of its normal control by nerves, including diarrhoea, constipation and slow transit disorders. Chronic and debilitating derangement of intestinal function occurs in irritable bowel syndrome, which affects around 10-15% of people in our community, about 1% at any one time. Irritable bowel syndrome can persist for many years, and there is no adequate therapy. For some patients no medication gives relief, and for most the relief is minimal. The refl ....The intestine is subject to a number of disorders of its normal control by nerves, including diarrhoea, constipation and slow transit disorders. Chronic and debilitating derangement of intestinal function occurs in irritable bowel syndrome, which affects around 10-15% of people in our community, about 1% at any one time. Irritable bowel syndrome can persist for many years, and there is no adequate therapy. For some patients no medication gives relief, and for most the relief is minimal. The reflexes in the intestine that control its movements and secretion depend for their initiation on a special type of neuron, known as the intrinsic primary afferent neuron. These neurons have properties that determine how active they are. These properties distinguish them from all other enteric neurons. If the activity of intrinsic primary afferent neurons is controlled, then the intensity and character of enteric reflexes are also controlled. Thus it is feasible to target molecules in these neurons that could be used to treat constipation or diarrhoea, or to accelerate movement of food along the intestine. Our work has identified molecular targets and some of the medicinal compounds that could be useful to patients. The project will further define the molecular targets, determine the specificity of potential treatments and test the effectiveness of the medicinal compounds in an animal model.Read moreRead less
The key to how the brain works lies in its capacity to modify the strength of its connections. During development, input to the brain from our sensory organs shapes the properties of synaptic contacts and target neurons. This project is aimed at understanding the pathways in the brain related to our sense of hearing, and discovering what is different about these pathways in congenital deafness, where the brain does not receive the appropriate signals during development.
This research program aims to gain a detailed understanding of the organisation of the cell surface at the molecular level. The cell surface is organised into domains with distinct functions. Visualisation of these domains, identifying their important components, and understanding how they form and function will have huge importance for therapeutic strategies aimed at combatting the changes associated with cell transformation in cancer and in other human diseases such as muscular dystrophy.
Membrane Attachment And Components Of The Ca2+ -triggered Release Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$386,498.00
Summary
Understanding and harnessing the fundamental cellular process of secretion will provide a wealth of new approaches to addressing problems associated with aging & disorders that are major health care burdens (e.g. neurodegeneration & diabetes). Understanding the vesicle docked state, and the contributions of different molecular components to the release process provides for unique insights into the underlying molecular mechanisms, thereby enabling safe, targeted control of this critical process.
Multiscale Analysis Of Plasma Membrane Microdomains In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$863,413.00
Summary
The cell surface encloses the cell in a protective barrier but it must also respond to signals coming from outside the cell. To accomplish this, the cell surface is made up of numerous regions each with a specialised role. This proposal aims to examine how lipids and proteins work together to make these specialised regions and aims to understand what goes wrong in diseases such as muscular dystrophy.
The regulation to early T cell signalling is a critical step in immune responses. Superimposed onto the biochemical pathways is a spatial organization that defines the immunological synapse. My research aims to map the principles of the spatial organization on the molecular scale to identify how lipids could unbalance the dynamic signalling equilibrium, for example in obese patients. To achieve this goal, my research group has developed single molecule microscopy approaches.