What Factors Affect Lesion Distribution In Multiple Sclerosis And Experimental Autoimmune Encephalomyelitis?
Funder
National Health and Medical Research Council
Funding Amount
$56,797.00
Summary
Multiple sclerosis (MS) is a common neurological disease which affects about 10,000 people in Australia. In MS, a persons own immune system starts to attack specific parts of their brain and spinal cord, causing lesions that prevent nerve impulses from passing from the brain to other parts of the body. The symptoms that people with MS develop can vary from one person to another, depending on where in the brain or spinal cord the lesions occur. Some parts of the brain and spinal cord seem to be m ....Multiple sclerosis (MS) is a common neurological disease which affects about 10,000 people in Australia. In MS, a persons own immune system starts to attack specific parts of their brain and spinal cord, causing lesions that prevent nerve impulses from passing from the brain to other parts of the body. The symptoms that people with MS develop can vary from one person to another, depending on where in the brain or spinal cord the lesions occur. Some parts of the brain and spinal cord seem to be much more susceptible to this attack than others, and the question that this study will address is why do lesions occur where they do in MS? Some preliminary results strongly suggest that there is a link between carrying particular genes that control immune responses, having immune cells that can attack one particular protein in the nervous system called PLP, and developing lesions in parts of the brain that control balance. This will be investigated further, and we will also look for other links between immune cells that can attack other proteins and development of lesions in particular areas. If such links can be identified, they would be very important for improved diagnosis of MS and it would enable more specific treatments for MS to be developed. We will also use experimental models of MS to investigate the exact components within the nervous system and within the immune system that play a role in directing the attack to particular sites.Read moreRead less
Heterogeneous Nuclear Ribonucleoprotein A2-dependent MRNA Trafficking In The Cytoplasm Of Cells.
Funder
National Health and Medical Research Council
Funding Amount
$346,650.00
Summary
Control of the use of DNA, gene expression, is vital to all living organisms, especially in development and disease. The information in the genes of DNA is transferred to an intermediate molecule, mRNA, in a process called transcription. The genetic information in the mRNA is subsequently used 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 ....Control of the use of DNA, gene expression, is vital to all living organisms, especially in development and disease. The information in the genes of DNA is transferred to an intermediate molecule, mRNA, in a process called transcription. The genetic information in the mRNA is subsequently used 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. The RNA molecules may be confined to a small region of the cell, resulting in the localization of the protein produced from it; the RNA may be rapidly degraded or stabilized; and the efficiency of production of the protein from its RNA precursor may be modulated by other molecules. It had previously been shown that the mRNA encoding a protein that is an essential structural component of central nervous system myelin is selectively transported to the regions in the cell where the myelin is made. We have identified the molecule that recognises this RNA as a protein called hnRNP A2 and shown how it selects the RNA molecules that have to be transported from the myriad of RNA moleclues in the cell at any given time. hnRNP A2 was previously thought to be confined to the nuclei of cells, but we have shown that it is also present outside the nucleus and is involved in RNA transport in a variety of cell types. hnRNP A2 appears to be directly involved in rheumatoid arthritis, lung cancer and other cancers. It has been proposed as a diagnostic test for cancer as elevated intracellular levels and circulating antibodies against this protein appear before the cancerous cells are visible under the microscope. The major aim of the proposed project is to explore the molecular mechanism by which hnRNP A2 transports RNA molecules in cells.Read moreRead less
Role Of ABCA8 Transporter In Oligodendroglial Lipid Regulation And Multiple System Atrophy
Funder
National Health and Medical Research Council
Funding Amount
$651,516.00
Summary
Multiple system atrophy (MSA) is a rapid-onset brain disorder impacting on multiple functions of the body resulting in death. The cause of MSA is unknown and there is no cure. In MSA brains, the oligodendroglial cells are impaired and cannot properly make myelin (specialized lipid membrane), which is required for the proper functioning of the nerve cells in the brain. The aim of this project is to find out how changes in lipid in the brain impact on the MSA disease process.
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