Novel Regulation Of RDNA Transcription By MTOR/S6K Signalling
Funder
National Health and Medical Research Council
Funding Amount
$393,750.00
Summary
Increased cellular growth requires a number of important processes to occur, the most fundamental of which is protein synthesis. Successful synthesis of proteins requires a large number of efficient ribosomes, the protein synthesis machinery. mTOR is a central cellular signalling molecule that directly regulates growth via modulating the efficiency of the ribosomes. It does this by regulating an enzyme called S6 kinase. Interestingly for long term or sustained increases in the rates of growth an ....Increased cellular growth requires a number of important processes to occur, the most fundamental of which is protein synthesis. Successful synthesis of proteins requires a large number of efficient ribosomes, the protein synthesis machinery. mTOR is a central cellular signalling molecule that directly regulates growth via modulating the efficiency of the ribosomes. It does this by regulating an enzyme called S6 kinase. Interestingly for long term or sustained increases in the rates of growth an increase in the number of ribosomes in addition to an increase efficiency of protein synthesis is required. This proposal will test the hypothesis that the mTOR-S6 kinase signalling pathway regulates protein synthesis both at the level of ribosome efficiency and capacity. This will be extended to determine the mechanism by which such regulation occurs. Furthermore recent studies have demonstrated that S6 kinase is involved in tumor growth. We propose that S6 kinase will contribute to the regulation of both normal or tumor growth at least in part via modulation of the number of ribosomes. Accordingly, S6K is upregulated in a segregated proportion of breast tumors. Outcomes from this project have the potential to provide targets to which specific therapies for particular breast tumors can be developed. Overall this information will also extend our basic knowledge on normal growth regulation.Read moreRead less
TorsinA Mediated Dystonia, Functional Analysis And Molecular Models
Funder
National Health and Medical Research Council
Funding Amount
$479,817.00
Summary
The dystonias represent a group of movement disorders characterised by sustained muscle contraction, resulting in twisting and abnormal postures. Current treatment regimes may provide some measure of symptomatic relief, but are often unsatisfactory and limited by adverse side effects. The prevalence of dystonia is estimated at approximately 300 cases per million population. Dystonia is a complex disorder, the causes and disease mechanisms are not well understood. However, in the past 10 years se ....The dystonias represent a group of movement disorders characterised by sustained muscle contraction, resulting in twisting and abnormal postures. Current treatment regimes may provide some measure of symptomatic relief, but are often unsatisfactory and limited by adverse side effects. The prevalence of dystonia is estimated at approximately 300 cases per million population. Dystonia is a complex disorder, the causes and disease mechanisms are not well understood. However, in the past 10 years several genes have been identified that can cause dystonia. The overall aim of this proposal is to characterise a gene that causes dystonia when disrupted. Understanding the function of this gene may significantly advance our understanding of this disorder. Using these results, we aim to model dystonia in cellular and animal systems; these may provide powerful insight into the molecular pathway(s) perturbed in dystonia and a means to develop novel therapeutic approaches to alleviate or prevent the disorder.Read moreRead less
A Single Fibre Approach To The Study Of Regulation Of Protein Synthesis In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$420,039.00
Summary
Skeletal muscle is the most abundant tissue in the human body and accounts for more than 40% of body weight. Loss of muscle mass is a major cause of frailty and loss of functionality in the elderly and is also a common feature of many chronic diseases such as cancer, HIV, arthritis and chronic heart failure. Changes in protein synthesis are intrinsically associated with alterations in muscle mass, which is integral to health, physical performance and independent living. In this project we aim to ....Skeletal muscle is the most abundant tissue in the human body and accounts for more than 40% of body weight. Loss of muscle mass is a major cause of frailty and loss of functionality in the elderly and is also a common feature of many chronic diseases such as cancer, HIV, arthritis and chronic heart failure. Changes in protein synthesis are intrinsically associated with alterations in muscle mass, which is integral to health, physical performance and independent living. In this project we aim to answer some important outstanding questions regarding the regulation of protein synthesis in mammalian skeletal muscle using a novel, single cell approach. Results obtained within the framework of the project will contribute to the understanding of the regulation of cellular and molecular events underpinning protein synthesis in muscle, which is critical for developing effective strategies of treatment and management of various medical conditions to prevent muscle wasting.Read moreRead less