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.
Neural Control Of Behavioural State And Cognition - Role Of Nucleus Incertus And Relaxin-3
Funder
National Health and Medical Research Council
Funding Amount
$600,771.00
Summary
Dementia and mental illness are significant social and economic burdens worldwide and knowledge of underlying causes and more effective therapies are required. Our research is using preclinical models to characterize a little studied neural network in the control of arousal states, rhythmic brain activity, and learning and memory. Our findings could advance the development of improved treatments for cognitive deficits in degenerative, age-related and psychiatric disorders.
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.
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.
The exciting field of small RNA research was the subject of the 2006 Nobel Prize in Medicine, and holds great potential in the diagnosis and prognosis of disease such as cancer. Recent clinical studies suggest that drugs inhibiting small RNAs called microRNA present novel therapeutic opportunities. By defining the non-specific effects of such drugs and investigating new avenues for their delivery, this project will secure the safe application of these drugs into the clinic.
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.
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.
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.