Protein / Protein Interactions Important For AMP-activated Protein Kinase Regulation
Funder
National Health and Medical Research Council
Funding Amount
$242,545.00
Summary
The AMP-activated protein kinase (AMPK) is an enzyme that monitors the energy levels of the body. When oxygen and nutrient levels decrease, the energy levels of a cell also decrease leading to activation of the AMPK. This results in activation of energy-producing pathways and inhibition of energy-consuming pathways, allowing cells to match supply with demand to ensure their survival. The AMPK comprises of three proteins that together form a functional enzyme. In this application I aim to obtain ....The AMP-activated protein kinase (AMPK) is an enzyme that monitors the energy levels of the body. When oxygen and nutrient levels decrease, the energy levels of a cell also decrease leading to activation of the AMPK. This results in activation of energy-producing pathways and inhibition of energy-consuming pathways, allowing cells to match supply with demand to ensure their survival. The AMPK comprises of three proteins that together form a functional enzyme. In this application I aim to obtain a thorough understanding of the molecular basis of how the AMPK functions. I will determine how and where the three proteins interact with each other and determine where in a cell at any given time the AMPK can be found. This is an important question to answer because many proteins are inactive within the cytoplasm but when they are bound to the plasma membrane they are active. I have previously found the AMPK to be localized to the cytoplasm, membrane and nuclear compartments of the cell, but little is known about the AMPK s function in these different locations. Activation of the AMPK is known to depend on another protein that is also activated when cellular energy levels decrease. This protein has remained elusive to many researchers over the past few years. I plan to identify this protein using new bioinformatics together with the vast amount of information provided by the sequencing of the human genome. Exercise and reduced caloric intake activate the AMPK, these are associated with health benefits and reduce the risk of cardiovascular and neurodegenerative diseases, diabetes and obesity. For these reasons information on the role of the AMPK may improve our understanding of the reasons these diseases develop.Read moreRead less
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
The Interactions Of Dengue Virus RNA Dependent RNA Polymerase (NS5) With Other Viral And Host Factors.
Funder
National Health and Medical Research Council
Funding Amount
$170,165.00
Summary
Dengue fever is a mosquito-borne disease that is prevalent in tropical countries. It is estimated that 40% of the global population is at risk of dengue infection. Classical dengue fever is not life threatening. However, the more serious disease, dengue haemorrhagic fever-shock syndrome requires intensive medical attention to prevent fatality. A significant number of deaths are recorded each year especially in the underdeveloped countries. Dengue is periodically also a problem in northern Austra ....Dengue fever is a mosquito-borne disease that is prevalent in tropical countries. It is estimated that 40% of the global population is at risk of dengue infection. Classical dengue fever is not life threatening. However, the more serious disease, dengue haemorrhagic fever-shock syndrome requires intensive medical attention to prevent fatality. A significant number of deaths are recorded each year especially in the underdeveloped countries. Dengue is periodically also a problem in northern Australia. There is no cure for dengue fever. The present research aims to use a knowledge-based approach to develop novel antiviral strategies based on preventing the critical protein interactions required for the normal virus life cycle. Two of the most important proteins involved in dengue virus replication are called the NS3 and NS5 proteins. The protein-protein interaction (contact) that occurs between NS5 and NS3 is crucial for the replication of the virus. Little is known about this interaction at present, and the studies we propose will directly address this issue. We have previously shown that a 37 amino acid in the middle of NS5 contains a nuclear localisation signal that can target the normally cytoplasmic protein to the nucleus of the infected cell. What the function of this protein is in the nucleus is not known. We will use a technique called the yeast two-hybrid test to address the question of dengue virus protein interactions in the common bakers yeast. This method is very sensitive and powerful and will provide important insights that will contribute to the development of a rapid high-throughput test to screen the extensive extract collection from Australia's marine biodiversity, held by the Australian Institute of Marine Sciences, to discover suitable inhibitors of NS3-NS5 interaction.Read moreRead less