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
Mechanism Of Interaction Of VWC Domains And Consequence For Protein Function
Funder
National Health and Medical Research Council
Funding Amount
$516,803.00
Summary
More than 1000 proteins contain a type of module known as the VWC domain. These domains are discreet sections of the protein that are very important for how the protein works. Proteins containing this domain are involved in normal functioning of the human body and in diseases of the nervous system and blood, among others. The main function of the VWC domain is to link proteins together in complexes. How this is achieved is not known and is what we aim to discover.
Recent evidence suggests that the Siah proteins are involved in sensing low oxygen levels in cells, and subsequently activating processes to help the cell survive under these conditions. Low oxygen conditions occur in cancer and sites of inflammation, suggesting that inhibiting Siah may improve patient outcomes in diseases such as cancer and arthritis. We aim to perform a high throughput screen for drugs that inhibit Siah protein function and to test these in cancer cells.
Role Of FHA Domains As Protein-protein Interaction Modules In Cell Signalling
Funder
National Health and Medical Research Council
Funding Amount
$191,973.00
Summary
The proper processing of information in cells involves the association of different proteins to signalling complexes. We will decipher the role the so-called FHA module plays in the formation of protein complexes. FHA modules are present in several proteins that are important for the repair of damaged DNA and the stability of chromosomes. Understanding the structure and function of this module will be relevant for various forms of cancer where DNA is damaged.
Investigation Of An LMO4- And BRCA1 -containing Complex Involved In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$440,250.00
Summary
Breast cancer will affect one in twelve Australian women and a quarter of those will die from breast cancer. At present we still know little about what causes the disease, and there is currently a lot of activity in the field of breast cancer research that will ultimately increase our ability to both detect its development at early stages and to provide effective treatments for the disease. We do know that losing the function of a few genes (breast cancer susceptibility genes) leads to a very hi ....Breast cancer will affect one in twelve Australian women and a quarter of those will die from breast cancer. At present we still know little about what causes the disease, and there is currently a lot of activity in the field of breast cancer research that will ultimately increase our ability to both detect its development at early stages and to provide effective treatments for the disease. We do know that losing the function of a few genes (breast cancer susceptibility genes) leads to a very high likelihood of developing cancer, and we know that the normal roles of the proteins that are produced from these genes are to prevent cancers from occurring in a spontaneous fashion. However, the inheritance of mutations in breast cancer susceptibility genes accounts for only a few percent of breast cancer cases. A recently discovered protein, known as LMO4, has been found at abnormal levels in over 50% of non-inherited breast tumors. This protein has been found to both interact with the protein from the most commonly occurring breast cancer susceptibility gene, known as BRCA1, and to prevent the normal activity of BRCA1. Thus, if we could develop reagents that prevent LMO4 from interacting with BRCA1, we could use those reagents as lead compounds for the development of anti-breast cancer drugs. Before we can develop such reagents we need to fully understand both what these proteins look like and how they interact. We already know that two other proteins, known as ldb1 and CtIP are involved in the LMO4:BRCA1 interaction. We will investigate the ways in which all of these proteins interact, from determining how strong each interaction is, to getting atomic level information about which surfaces of the proteins make the most contribution to each interaction. This should let us identify good targets for the design and development of anti-breast cancer drugs.Read moreRead less