A Genome Wide Screen For Human Genes That Support The Replication Of Intracellular Bacterial Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$321,090.00
Summary
Coxiella burnetii is a bacterium that causes a life threatening infection of humans, termed Q fever.Coxiella survives and replicates inside human cells within a unique protected niche and little is known about how the bacterium does this. This study will identify and investigate the individual human proteins that are used by the bacterium to manipulate the human cells it inhabits and the mechanisms through which the bacterium achieves this.
Control of the use of DNA, gene expression, is vital to all living organisms, especially in development and disease. The information in the genes 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 ....Control of the use of DNA, gene expression, is vital to all living organisms, especially in development and disease. The information in the genes 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. In this project we will investigate the molecular mechanisms of several proteins, heterogeneous nuclear ribonucleoproteins (hnRNPs), that appear to play regulatory roles in many of these steps. These proteins appear to affect the longevity and replication of cells, the important chemical changes that take place in RNA after it is transcribed and before it is translated, the movement of the modifed RNAs through the cell and the efficiency of translation. Because of these central functions they are involved in development of tissues such as the brain, and in diseases including lung, skin and brain cancers, and rheumatoid arthritis. In this project we will focus on two RNA molecules, one vital for myelination in the central nervous system and the other for memory.Read moreRead less
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.
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.
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.
An unusual type of molecule, circular RNA, was recently discovered to be present in human cells, and to potentially affect the ability of cancer cells in invade and metastasise. We will investigate the interactions these circular RNA molecules have with other molecules, what functions they have, and how they affect cancer cell invasion and metastasis. This could potentially reveal new ways of intervening in cancer metastasis, leading to new therapeutic modalities for cancer patients.
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.