Mechanisms And Patterns Of Post-Transcriptional Gene Control
Funder
National Health and Medical Research Council
Funding Amount
$707,370.00
Summary
Genetic information resides in the DNA of our genome; however, to use this information it must be transcribed into chemically related RNA molecules, collectively known as the transcriptome. While different body cells carry the same genome, they differ widely in their transcriptome composition. To understand how cells properly utilise their transcriptomes we will characterise the marks and binding partners found on RNA in the context of cardiac and cancer biology.
Investigation Of 5-methylcytosine And MicroRNA Function In Eukaryotic RNA
Funder
National Health and Medical Research Council
Funding Amount
$311,991.00
Summary
It is hypothesised that 5-methylcytosine in RNA represents a novel regulatory code affecting transcriptome utilisation in ways currently hidden from view. To unravel this code and its (patho)- physiological role(s), this study proposes to generate and interpret comprehensive transcriptome-scale maps of 5-methylcytosine in a range of cellular contexts chosen to reveal links to cellular differentiation, growth, and malignant transformation.
Protein-RNA Interactions In Antiviral Cellular Defence And Gene Regulation
Funder
National Health and Medical Research Council
Funding Amount
$705,501.00
Summary
Protein-RNA interactions play key roles in antiviral cellular defence and inflammation. Investigation of these molecular interactions will lead to new therapeutic targets and means of combating virus-related disease and inflammatory disorders.
Characterising The Topology And Function Of The Human M5C RNA Methylome
Funder
National Health and Medical Research Council
Funding Amount
$602,537.00
Summary
The role of the modified base 5-methylcytosine (m5C) as an epigenetic mark in DNA is well appreciated and intensely studied. By comparison, the cellular functions of the same base modification in RNA molecules, which function as working copies of the DNA genome, are poorly understood. This project will apply next generation sequencing technology to chart the occurrence of m5C in eukaryotic cellular RNAs and endeavour to unravel its function(s) in human biology and cancer.
The Role Of The HuB RNA-binding Protein In Post-transcriptional Gene Regulation In The Pre-gastrula Zebrafish Embryo
Funder
National Health and Medical Research Council
Funding Amount
$545,216.00
Summary
The precise control of protein expression is absolutely critical in biology. The key decisions about which genes are turned on or off at any one moment control the proper growth of an organism during development, and are responsible for the organism's homeostasis and proper response to environmental changes as an adult. The spatio-temporal control of genes is critcal during embryogenesis and we aim to understand how these processes underlie development in the vertebrate embryo.
Identifying Target Molecules Regulated By Nuclear Retention In Cancer And Development
Funder
National Health and Medical Research Council
Funding Amount
$267,173.00
Summary
Human DNA contains approximately 30000 genes; only twice as many as worms and flies, ten times as many as bacteria, and fewer than rice. Humans, however have considerably more complexity than these lower organisms. What are the factors responsible for the additional complexity? In the simplest scenario, one gene is transcribed to produce one message (mRNA), which is the blueprint for producing one protein. We now know that there are numerous mechanisms that potentially allow many different prote ....Human DNA contains approximately 30000 genes; only twice as many as worms and flies, ten times as many as bacteria, and fewer than rice. Humans, however have considerably more complexity than these lower organisms. What are the factors responsible for the additional complexity? In the simplest scenario, one gene is transcribed to produce one message (mRNA), which is the blueprint for producing one protein. We now know that there are numerous mechanisms that potentially allow many different proteins to be made from one gene. Also, it is the decisions about which gene will be made ( expressed ) into protein where and when in development, that is critical for our complexity. The control of gene expression is thus fundamental to all cellular processes and many diseases such as cancer and metabolic disorders are associated with some aspect of aberrant gene expression. The production of mRNA from DNA occurs in the human cell nucleus. The nucleus is not simply a bag of DNA, in fact, many important nuclear factors are organised into sub-nuclear bodies . Recently we discovered a novel sub-nuclear body, the paraspeckle and have been identifying its components and their function. Paraspeckles are involved in a previously undiscovered mechanism of the control of gene expression. Here, certain mRNA molecules are trapped in the nucleus until a signal is received from elsewhere in the cell, which causes the mRNA to be released and protein to be made. This Rapid Release Nuclear Retention mechanism effectively allows the quick production of specific proteins to be made on demand. In this project we propose to use cutting edge molecular and cell biology techniques to identify the special mRNA molecules that are trapped in paraspeckles in cancer cells. This will increase our understanding about the molecular details of this process, ultimately leading to potential uses in gene therapy, and should result in the discovery of important targets for cancer treatment.Read moreRead less