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Regulation And Substrate Identification Of Parkinsons Disease Causative Leucine-rich Repeat Kinase 2 (LRRK2)
Funder
National Health and Medical Research Council
Funding Amount
$699,456.00
Summary
Parkinson's disease afflicts 100,000 Australians. Mutations in the recently identified enzyme Leucine-rich Repeat Kinase-2 are a common cause of Parkinson's disease. This project will use biochemical methods to understand how this brain enzyme causes disease by investigating its enzymology, modes of regulation, and target substrates that it modifies by addition of phosphate groups. Characterization of this enzyme will facilitate design of inhibitors to slow the course of Parkinson's disease.
Neural Coding Of A Cue To Auditory Space, In Noisy Environments
Funder
National Health and Medical Research Council
Funding Amount
$180,160.00
Summary
GENERAL BACKGROUND : Our ability to determine where a sound is coming from (localization ability) is severely disrupted when the environment is noisy. This affects our abilities at many ordinary tasks, such as keeping up a conversation in a noisy background, and also in other critical tasks (eg., in following warning signals in a noisy factory environment). In people who have some hearing loss, even if only partial deafness, localization ability is disrupted even when there is no noise in the ba ....GENERAL BACKGROUND : Our ability to determine where a sound is coming from (localization ability) is severely disrupted when the environment is noisy. This affects our abilities at many ordinary tasks, such as keeping up a conversation in a noisy background, and also in other critical tasks (eg., in following warning signals in a noisy factory environment). In people who have some hearing loss, even if only partial deafness, localization ability is disrupted even when there is no noise in the background, and is even more severely disrupted when the environment is noisy. SCIENTIFIC BACKGROUND : Our localization ability depends on the way neurons in the brain code the position of a source of sound we wish to detect. From studies in animals we know a lot about the way in which neurons do this coding in silence. However, we know almost nothing about how this coding is affected by a noisy background. Further, we know absolutely nothing about how this coding, whether in silence or when there is noise, is affected when there is also a hearing loss. SIGNIFICANCE : If we are to understand the effects of hearing losses on coding of the location of a sound signal we need to know first how noise affects the coding in cases of normal hearing. This project aims to gain that information. I will then extend this to studying the detailed basis of these effects, ie., exactly what mechanisms are affected in the neurons. Then I will determine how noise from different positions affects the coding of signal sounds at differnt positions. These data will provide us the essential base from which we can, later, go on to study how noise affects coding by neurons of the location of a signal. I plan to increase the value of the current study by developing, from the data gained in the studies in animals, computer-based models that will allow us to predict how coding of sound signal location is affected by hearing loss, and how this is exacerbated by noisy environments.Read moreRead less
Characterization Ol A Novel Covalently Cross -linked Abeta Peptide Dimer And Its Role In Alzheimers Disease.
Funder
National Health and Medical Research Council
Funding Amount
$553,236.00
Summary
Currently there are limited therapeutic treatments and no cure for Alzheimer's disease (AD). The key protein causing AD is called Abeta. Abeta peptides form dityrosine cross-linked dimers (when 2 peptides join together) and this is thought to be responsible for killing brain cells in AD. Therefore, this proposal will determine the role of Abeta dimers in relation to killing brain cells and the progression of AD through analysis of their biological and biochemical properties.