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.
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.
Codon Bias: A Hidden Layer Of Translational Regulation By Estrogens
Funder
National Health and Medical Research Council
Funding Amount
$420,922.00
Summary
The hormone estrogen signals through its receptors to mediate both transcription in the nucleus and signalling known to affect translation in the cytoplasm. It is currently unknown in which way the response to estrogen is orchestrated by integrating the translation of messenger RNAs with the transcription of target genes. The project aims to determine how estrogen signalling is integrated by carefully dissecting how messenger RNAs are transcribed and translated under its control.
Exploring The Role Of MicroRNA And Target Processing Variability In Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$605,190.00
Summary
microRNAs are gene regulators with critical roles in heart disease. How interactions between microRNAs and their messenger RNA targets change during disease is poorly understood. We hypothesise that these interactions are critically affected by altered processing of microRNAs and targets. We will thus characterise and validate such differences in healthy and diseased hearts. This will define gene regulatory changes underpinning heart disease and contribute to the search for better treatment.
Charting The Interface Between Cellular Metabolic States And Gene Regulation
Funder
National Health and Medical Research Council
Funding Amount
$653,196.00
Summary
The research successes of Molecular Biology and Biochemistry have given us detailed pictures of the regulatory and metabolic states of cells and tissues, yet we know little about how these states affect each other. We hypothesise the existence of regulatory interactions between ribonucleic acids, enzymes and metabolites to connect gene expression and metabolism. We will employ novel RNA Biology methods to discover such regulatory interactions in medically important cellular contexts.
Pathways That Regulate Nuclear Export Of Circular RNA
Funder
National Health and Medical Research Council
Funding Amount
$933,327.00
Summary
An emerging and unusual class of RNA molecules, circular RNAs (circRNAs), is widespread and plays important roles in cancer initiation and progression. However, the pathways responsible for nuclear export of circRNAs are unknown. We propose here to systematically determine how circRNAs are exported from the nucleus and characterise the effect of modulating circRNA export pathways in cancer. This will enable us to determine whether circRNAs can function as a biomarker of patient response.
Understanding The Role Of Circular RNAs In Neuronal Biology Using RNA-targeting CRISPR/Cas9
Funder
National Health and Medical Research Council
Funding Amount
$398,097.00
Summary
The regulation of gene expression through a process known as RNA splicing has been shown to be at the heart of a number of processes required for brain development, memory and learning, and is often dysregulated in a number of neurological diseases. Circular RNAs (circRNAs) have been recently shown to be a relatively abundant class of spliced RNA that are specifically enriched in brain tissue. In this project, I aim to understand the roles of circRNAs in neuronal development.
Molecular Basis For RIG-I Like Receptor Activation Of The Innate Immune Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$564,770.00
Summary
This project is to understand how proteins in the cell detect the presence of invading viruses, and pass on the message for the cell to produce defence molecules. The overproduction of these defence molecules can lead to inflammatory diseases. This research will help us to understand the process of the innate immune response in cells and how we might control it in disease states.
MRNA Surveillance In Human Genetic Disease: Molecular Determinants Of Nonsense-mediated MRNA Decay
Funder
National Health and Medical Research Council
Funding Amount
$371,275.00
Summary
In about 1/3 of inherited disorders the mutations introduce an abnormal stop signal into the gene so that cells risk producing truncated or erroneous proteins. To prevent this cells have developed control surveillance mechanisms called Nonsense Mediated mRNA Decay (NMD). We have found a new form of NMD and our studies are directed determining how this works in cells, which genes use this pathway, and the consequences of this for human genetic disease.