Understanding The Physiological Role Of COUP-TF Orphan Nuclear Receptors In Skeletal Muscle.
Funder
National Health and Medical Research Council
Funding Amount
$454,923.00
Summary
COUP-TF is a protein expressed in skeletal muscle, a tissue that accounts for ~40% of the body mass and energy expenditure, and is a major site of nutrient metabolism. COUP-TF is a member of the nuclear hormone receptor (NR) superfamily. These proteins respond to physiological signals, and are targets of pharmaceuticals for the treatment of inflammation, metabolic and endorcrine disorders. Our project is directed toward understanding the role of COUP-TF in the context of metabolism and obesity.
A major feature ofcancer is accelerated cell growth and proliferation. One of the major rate-limiting processes that regulates cell growth is the synthesis of ribosomes (the protein synthetic machinery). This study will examine a factor termed UBF whose activity is critical for the regulation of ribosome synthesis. It wll also explore the hypothesis that dysregulation of ribosome biogeneis underlies and contributes to the aetiology of many human cancers.
Heterogeneous Nuclear Ribonucleoprotein Role In Alternative RNA Splicing And Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$254,250.00
Summary
Control of the use of DNA, gene expression, is vital to all living organisms, especially in development and disease. The information in the genes of DNA is transferred to an intermediate molecule, mRNA, in a process called transcription. The genetic information in the mRNA is subsequently used, in the process called translation, to make the protein encoded by the original gene. The switching on and off of DNA appears to be most frequently controlled at the transcription step but recently it has ....Control of the use of DNA, gene expression, is vital to all living organisms, especially in development and disease. The information in the genes of DNA is transferred to an intermediate molecule, mRNA, in a process called transcription. The genetic information in the mRNA is subsequently used, in the process called translation, to make the protein encoded by the original gene. The switching on and off of DNA appears to be most frequently controlled at the transcription step but recently it has become apparent that there are many post-transcriptional events that govern how efficiently the genetic information is ultimately converted to protein molecules. An important step is the cutting out of parts (introns) of the RNA molecule that is copied from DNA, and splicing of the retained sections (exons). During this process the RNA may also lose one or more of its exons. As a result of this variable retention of exons a single gene may produce many isoforms of the protein it encodes. By this mechanism the roughly 30,000 genes in the human genome can give rise to potentially hundreds of thousands of proteins. RNA splicing connects to cancer in two ways. First, changes in the concentrations of the proteins that control splicing may change the isoforms, resulting in changes that lead to uncontrolled cell proliferation. Secondly, DNA mutations that affect the splicing process can also vary the ratios of the isoforms produced from a gene: if this occurs in a protein that is involved in the growth of cells this too may lead to cancer. In this project we will study the molecular mechanism of this alternative splicing, and particularly a group of proteins that generally favour the excision of some exons, with a focus on cancer cells. Recent publications have highlighted the potential for the therapeutic use of drugs that target the splicing apparatus: it is anticipated that studies of alternative splicing will underpin development of new therapeutic agents.Read moreRead less
Investigating the role of gene loops in regulating gene expression. The ability to identify functional variants in regulatory elements will have implications for researchers in multiple fields of biology, from molecular medicine to agriculture. Transfer of expertise and application of the knowledge generated by our research to such fields stands to improve diagnosis of disease predisposition and to improve quality of animal and plant products. These outcomes will benefit all Australians. This kn ....Investigating the role of gene loops in regulating gene expression. The ability to identify functional variants in regulatory elements will have implications for researchers in multiple fields of biology, from molecular medicine to agriculture. Transfer of expertise and application of the knowledge generated by our research to such fields stands to improve diagnosis of disease predisposition and to improve quality of animal and plant products. These outcomes will benefit all Australians. This knowledge will also improve the education of Australian University students as it contributes to the development of advanced curricula and access to more powerful research methods. In addition, the project will foster important collaborations between Australian researchers and those overseas.Read moreRead less
The body tightly controls when and where proteins are made. Likewise once a protein has performed its function, it must be removed. Targeted proteolysis serves to reset the cell so that it can respond anew to stimuli that trigger growth and cell development. The Siah proteins are a family of proteins that control the turnover of other proteins. Siah proteins are remarkably highly conserved in evolution, and counterparts of the human proteins can be found in fruitflies, worms and plants. There ar ....The body tightly controls when and where proteins are made. Likewise once a protein has performed its function, it must be removed. Targeted proteolysis serves to reset the cell so that it can respond anew to stimuli that trigger growth and cell development. The Siah proteins are a family of proteins that control the turnover of other proteins. Siah proteins are remarkably highly conserved in evolution, and counterparts of the human proteins can be found in fruitflies, worms and plants. There are three different types of Siah protein in mice and this study investigates the function of the each protein by creating mice that lack one or more of these proteins. Our work to date has revealed that the Siah genes are involved in growth and fertility of mammals. The genes are also important for cell division, which implicates them in proliferative diseases such as cancer.Read moreRead less