Genome-wide Expression Analysis In Advanced Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$326,761.00
Summary
Gastric cancer is the fourth ranked cancer by mortality in Australia. Therapy of gastric cancer is unsatisfactory for two reasons; firstly, how normal stomach cells become cancerous is not well defined. We know long-term infection with the bacteria Helicobacter can lead to these cancers, as can severe acid reflux. The cancers produced by these very different agents look remarkably similar, but must be arising through different pathways. Research to date has not yielded great insight. Secondly, e ....Gastric cancer is the fourth ranked cancer by mortality in Australia. Therapy of gastric cancer is unsatisfactory for two reasons; firstly, how normal stomach cells become cancerous is not well defined. We know long-term infection with the bacteria Helicobacter can lead to these cancers, as can severe acid reflux. The cancers produced by these very different agents look remarkably similar, but must be arising through different pathways. Research to date has not yielded great insight. Secondly, existing therapy, especially chemotherapy, tends to provide a Oone size fits all? solution. Whatever the cause, removal at surgery is the best option for treatment. After this, patients are often treated with chemotherapy. Although improvements in patient comfort have been made, very few patients are cured as a result of this treatment. We need more information with which to match the right patient with the right therapy. We will perform high-throughput analysis of comprehensive arrays of human genes that are affected in gastric cancer. Biopsies from cancerous and normal tissue will be obtained when patients have surgery. This tissue will have the RNA (the Omessage? from each gene) labelled with chemical tags and then applied to DNA Omicrochips?. Each microchip contains about 5000 gene targets; the RNA binds the matching DNA and produces a light reaction. We can read the light output from these 5000 (or more) signals, and perform complex statistical analysis on the results. This will result in several specific Ogene expression profiles? which we will analyse to see which profiles match each situation. Profiles matching reflux-induced cancer and Helicobacter-induced cancer can be compared. This will suggest what unique processes are occurring in the cancer cells. Profiles of patients responding well to therapy may allow the use of Otailor-made? therapy. In the future, insight into cancer pathways should also allow the design of new and more successful therapies.Read moreRead less
Defining The Role Of RNA Editing In Erythropoiesis
Funder
National Health and Medical Research Council
Funding Amount
$628,945.00
Summary
We are seeking to understand how red blood cells are produced. We have identified that a process called RNA editing may be important in the regulating the production of red blood cells.
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.
The Characterization Of A Novel Pseudokinase Regulator Of Platelet Formation
Funder
National Health and Medical Research Council
Funding Amount
$372,965.00
Summary
Mammalian cells contain a complex switchboard, which directs the cell to grow, die, multiply or move in response to external cues. When communication breaks down within the cell, diseases arise. Our studies are directed towards identifying the molecules that comprise the switchboard which directs blood cell formation. A detailed understanding of the regulators of blood cell formation will equip us with a sound starting point for designing drugs to ameliorate blood diseases.
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.