Retroviral Recombination, RNA Dimers & Multiple Drug Resistant HIV-1
Funder
National Health and Medical Research Council
Funding Amount
$405,017.00
Summary
The emergence of multiple drug resistant strains of HIV-1 has threatened the continue success of current clinical treatment to suppress virus propagation. Retroviruses, such as HIV-1, can reshuffle its two copies of genetic materials during the viral replication process, which leads to the production of offspring viruses that contain a mixture of the parental genetic materials. This process of genetic information reshuffling is believed to be important for the generation of multiple drug resista ....The emergence of multiple drug resistant strains of HIV-1 has threatened the continue success of current clinical treatment to suppress virus propagation. Retroviruses, such as HIV-1, can reshuffle its two copies of genetic materials during the viral replication process, which leads to the production of offspring viruses that contain a mixture of the parental genetic materials. This process of genetic information reshuffling is believed to be important for the generation of multiple drug resistant strains of HIV-1. The objective of this proposal is to define the parameters that regulate the reshuffling of HIV-1 genetic materials and to design novel tools to inhibit the production of multiple drug resistant HIV-1.Read moreRead less
Human immunodeficiency virus type 1 (HIV-1) is the causative agent of AIDS. Recent advances with combination antiretroviral therapy have prolonged the survival time of HIV-1 infected patients, and provideed two important hints for a strategy to effectively treat this disease. First, administration of a combination of antiretroviral agents that target different stages of the viruses life cycle improves the clinical status of HIV-1 infected patients; and second, the formation of viral particles du ....Human immunodeficiency virus type 1 (HIV-1) is the causative agent of AIDS. Recent advances with combination antiretroviral therapy have prolonged the survival time of HIV-1 infected patients, and provideed two important hints for a strategy to effectively treat this disease. First, administration of a combination of antiretroviral agents that target different stages of the viruses life cycle improves the clinical status of HIV-1 infected patients; and second, the formation of viral particles during the HIV-1 replication cycle is an effective target for antiretroviral treatment, as demonstrated by the potency of drugs called protease inhibitors. A virus such as HIV is composed of viral proteins as well as genetic material called RNA. Two strands of viral RNA come together during the formation of HIV-1 in a process callered dimerization. It may be possible to interfere with RNA dimerization thus inhibiting HIV replication. This would provide a new target for HIV therapy. In order to do this, the process of RNA dimerization needs to be understood.The focus of this project is to define the mechanism of HIV-1 RNA dimerization, and to identify factors that are critical for virion RNA dimerization. Understanding the mechanism of virion RNA dimerization is likely to provide novel therapeutic target for the development of effective antiviral agents.Read moreRead less
Role Of Conformational Change In Activation Of The Growth Hormone Receptor
Funder
National Health and Medical Research Council
Funding Amount
$242,545.00
Summary
Growth hormone is an important hormone therapeutic for treating dwarfism. Recently, many new therapeutic applications for growth hormone have been discovered, particularly in relation to its role as an anabolic agent. These include post surgery recovery, enhanced bone fracture healing, Crohns disease, dilated cardiomyopathy, infertility and of course, ageing. This project seeks to find out how growth hormone sends its signal into the target cell through its surface receptor. It is believed that ....Growth hormone is an important hormone therapeutic for treating dwarfism. Recently, many new therapeutic applications for growth hormone have been discovered, particularly in relation to its role as an anabolic agent. These include post surgery recovery, enhanced bone fracture healing, Crohns disease, dilated cardiomyopathy, infertility and of course, ageing. This project seeks to find out how growth hormone sends its signal into the target cell through its surface receptor. It is believed that the primary event in signalling is the ability of the hormone to bring two receptors together (receptor dimerization). However, it may be that the receptor already is dimerized, and the role of the hormone is to induce a specific change in shape of the receptor, which transfers the signal of hormone binding into the cell to initiate signalling to the genome. We have good evidence that a specific shape change is required for activation of an important signalling pathway by growth hormone, and the closely structurally related receptor for erythropoietin is already dimerized before hormone binds. We want to find out exactly how the shape change acts, and whether the receptor is predimerized. This information is vital for designing small orally active mimics of growth hormone which could be of great value as an anabolic supplement for the frail elderly.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.