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.
Exploiting Messenger RNA Export As A Novel Therapeutic Strategy To Treat Cancer
Funder
National Health and Medical Research Council
Funding Amount
$948,098.00
Summary
Novel therapies for cancers represent an area of unmet clinical need. We have identified a new biological pathway implicated in cancer, namely selective mRNA export. Compounds inhibiting other steps of the gene expression pathway are promising therapeutic candidates for cancer, yet mRNA export inhibitors do not exist. We propose to develop first-in-class inhibitors of mRNA export that selectively target transcriptionally addicted cancers with dysregulated RNA processing.
Cell-specific Regulation Of The MicroRNA/RNAi Pathway
Funder
National Health and Medical Research Council
Funding Amount
$659,390.00
Summary
MicroRNAs are a group of molecules that are critical for controlling the activity of genes. They function in a diverse range of biological systems, such the brain and immune system. Although we know that these molecules are important, how they are made in cells is still poorly understood. Because these molecules have potential therapeutic applications, it is essential that we gain a precise understanding of their biology before we will be able to apply these to medicine.
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.
MicroRNAs are a group of molecules that are critical for controlling the activity of genes. They function in a diverse range of biological systems, from early embryonic development to adult organs, such as the brain and immune system. Although we know that these molecules are important, there remain major gaps in our understanding of how they are produced. Thus, the goal of our research is to understand how cells make these molecules.
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.
A New Function For Histone Variants In The Tissue-specific Regulation Of Pre-mRNA Splicing
Funder
National Health and Medical Research Council
Funding Amount
$657,224.00
Summary
It is estimated that greater than 90% of human genes undergo alternative RNA splicing, which can explain how protein diversity is achieved with a limited number of genes. However, how alternative splicing patterns are established remains poorly understood but is an important question given that 15-50% of human disease mutations are associated with changes to the splicing patterns of RNA. We have uncovered a new splicing mechanism, which involves changing the way DNA is packaged in a cell.
DBHS Protein RNA Interactions In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$748,073.00
Summary
In cells involved in cancer, the interactions of DBHS proteins with each other, and with nucleic acids (eg RNA) are different to those in healthy cells. Only once we understand how DBHS proteins interact with some important RNA molecules, and how these interactions affect cell biology, can we begin to open up new pathways for therapy. This proposal aims at understanding and explaining this complex aspect of biology.
Molecular Insights Into Long Noncoding RNA-protein Complexes: Important Gene Regulators In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$388,927.00
Summary
Cancer cells turn good genes off and bad ones on: but how do they do this? Recent breakthroughs suggest that noncoding RNA, produced from so-called ‘junk’ DNA, is important. One such noncoding RNA forms paraspeckles, a novel component of the cell machinery. Here, we will pick apart the way paraspeckles are organised and function, to develop them as a prototype for designing anti-cancer treatments against noncoding RNAs.