Localisation Of Genes For Multiple Sclerosis In The HLA Region
Funder
National Health and Medical Research Council
Funding Amount
$426,500.00
Summary
Multiple sclerosis (MS) is a disease that affects around 10,000 Australians. It is a disease of young adults with women being affected more often than men. While there are therapeutics available to treat it, these are very expensive ($10-12,000 per annum) and are effective in only a proportion of affected individuals. MS is governed by a complex interplay of environmental and genetic susceptibility factors, neither alone sufficient to cause disease, however, the study of these factors has been c ....Multiple sclerosis (MS) is a disease that affects around 10,000 Australians. It is a disease of young adults with women being affected more often than men. While there are therapeutics available to treat it, these are very expensive ($10-12,000 per annum) and are effective in only a proportion of affected individuals. MS is governed by a complex interplay of environmental and genetic susceptibility factors, neither alone sufficient to cause disease, however, the study of these factors has been confounded by the complex nature of the disease. We and other researchers have identified the human leukocyte antigen (HLA) complex on chromosome 6 as harbouring susceptibility genes for MS. Our recent work has localised these genes in two distinct regions of the HLA complex. In this project we plan to localise these genes more precisely to permit their identification. By identifying these genes we hope to develop an understanding of their function in a healthy person and in a person with MS. Understanding what goes wrong during disease is a critical first step along the track to the design of novel therapeutics. A successful therapeutic agent would be designed to interfere with disease processes and treat the disease more effectively.Read moreRead less
Major Histocompatibility Complex (MHC) Genetics Of Ankylosing Spondylitis
Funder
National Health and Medical Research Council
Funding Amount
$568,612.00
Summary
Ankylosing spondylitis (AS) is the prototypic condition of a group of types of inflammatory arthritis called 'seronegative spondyloarthropathies'. These conditions are the most common form of inflammatory arthritis in white populations and occur worldwide. One third of the risk of developing AS is determined by genes within a region called the 'major histocompatibility complex' (MHC), in addition to the gene HLA-B27, the main gene causing AS. We aim to identify the remaining MHC genes.
The Immunogenetics Of Ankylosing Spondylitis: A Genetic And Functional Investigation Of IL23R And Related Genes
Funder
National Health and Medical Research Council
Funding Amount
$536,679.00
Summary
Ankylosing spondylitis (AS) is a common inflammatory arthritis which causes primarily back pain and stiffness, and affects 1-250 individuals. Our group identified association between tagging genetic markers in the gene IL23R and AS, and our preliminary data suggests some related genes are involved as well. This study aims to identify the key genetic variants involved and determine the mechanism by which they cause AS.
THE CMRF-35 FAMILY OF MOLECULES: GENE STRUCTURE, EXPRESSION AND FUNCTION
Funder
National Health and Medical Research Council
Funding Amount
$367,669.00
Summary
White blood cells are the army which fights invasion by foreign organisms or cancer cells. Their main artillery and communication systems are located on the cell surface as protein molecules. These recognize foreign material and danger signals, and signal into the cell to direct interactions with other cells- soluble molecules in the immune system. We have discovered a new group of molecules called the CMRF-35 family which are found on the surface of different white blood cells. We have characte ....White blood cells are the army which fights invasion by foreign organisms or cancer cells. Their main artillery and communication systems are located on the cell surface as protein molecules. These recognize foreign material and danger signals, and signal into the cell to direct interactions with other cells- soluble molecules in the immune system. We have discovered a new group of molecules called the CMRF-35 family which are found on the surface of different white blood cells. We have characterized two members of the CMRF-35 family by studying the structure of their genes and the cells which express them. These studies will determine if the known CMRF-35 molecules are able to send signals from the cell surface into the cell to activate or inhibit a functional response by cells that express them. We hope to identify the triggers that initiate a signal from CMRF-35 molecules into the cell and whether there are molecules which bind CMRF-35 molecules and then get moved from the surface to inside the cell. Our data suggests that there are other unknown members of this family. We will determine how many members there are in this family by studying the DNA of genes that are related to the known CMRF-35 molecules. This will allow us to charactertize novel molecules that may be important for white cell function. Discovering new white cell surface molecules and determining their function increases our understanding of how the immune response works. If these CMRF-35 molecules represent a large family, it is highly likely that they have important roles in the immune response. By understanding the signals these molecules send to the cell nucleus we may be able to exploit their function to fight disease. For example where the immune system has not recognized cancer cells as dangerous, we might use the activating CMRF-35 molecules to stimulate a response. In the case of auto-immunity we may be able to reduce the responses via inhibitory CMRF-35 molecules.Read moreRead less