The maintenance of optimum health and function of living cells, and consequently that of the whole organism, depends on how cells respond to a multitude of physical and chemical stimuli that continually bombard them. The majority of the chemical stimuli such as hormones and neurotransmitters impart their actions not by directly entering the cell, but instead, by binding to a specific receiver protein at the cell surface called a receptor. In one class of such receptors called G protein coupled r ....The maintenance of optimum health and function of living cells, and consequently that of the whole organism, depends on how cells respond to a multitude of physical and chemical stimuli that continually bombard them. The majority of the chemical stimuli such as hormones and neurotransmitters impart their actions not by directly entering the cell, but instead, by binding to a specific receiver protein at the cell surface called a receptor. In one class of such receptors called G protein coupled receptors, the transmission of the message to the interior of the cell involves yet another protein called G protein. It is extremely important to unravel how each of these components, the stimulating agent, the receptor and G protein, works in order to understand how the cells respond to various chemical signals. To make this process even more complex, it was recently shown that another newly discovered group of proteins called receptor activity modifying proteins (RAMPs) too play a critical role in some systems. Understanding what actually is the role of these new players, and how they team-up with the other components to elicit a specific response to a chemical stimulus, forms the basis of this proposal. Such knowledge is central to the unraveling of the processes involved in the maintenance of health, abnormalities that lead to disease, and in the development of new treatments.Read moreRead less
Targeting The EGFR And C-Met Tyrosine Kinase Receptors In Myeloproliferative Neoplasms
Funder
National Health and Medical Research Council
Funding Amount
$607,559.00
Summary
We propose that in the blood disorders called Myeloproliferative Neoplasms (MPN) there are important changes that affect the function of receptors expressed on the surface of blood cells. These changes will perturb blood cell production and may be able to be targeted effectively with drugs. We will test this using laboratory-based and mouse models of MPN, together with specific drugs that are currently in the clinic, and that inhibit the activity of the key receptors involved. This approach can ....We propose that in the blood disorders called Myeloproliferative Neoplasms (MPN) there are important changes that affect the function of receptors expressed on the surface of blood cells. These changes will perturb blood cell production and may be able to be targeted effectively with drugs. We will test this using laboratory-based and mouse models of MPN, together with specific drugs that are currently in the clinic, and that inhibit the activity of the key receptors involved. This approach can be rapidly translated to clinical trial.Read moreRead less
Receptors form a basic intermediary as the acceptor site for signals that are transmitted between the cells that make up our body. Modulation of receptors, therefore, forms a key target in our ability to treat disease. The largest class of receptors is the superfamily of G protein-coupled receptors (GPCRs), which transmit signals within a cell via proteins called G proteins. GPCRs form between 1 and 5% of the entire repertoire of human genes. One group of GPCRs provide the target for small prote ....Receptors form a basic intermediary as the acceptor site for signals that are transmitted between the cells that make up our body. Modulation of receptors, therefore, forms a key target in our ability to treat disease. The largest class of receptors is the superfamily of G protein-coupled receptors (GPCRs), which transmit signals within a cell via proteins called G proteins. GPCRs form between 1 and 5% of the entire repertoire of human genes. One group of GPCRs provide the target for small protein molecules that circulate through the body. One such circulating molecule is calcitonin, a peptide that plays an important role in maintaining circulating calcium levels in the body, which is essential for proper maintenance of the skeleton. As a consequence of this action, calcitonin is an important clinically used tool in the treatment of bone disease such as osteoporosis and Paget's disease. Due to the molecular nature of calcitonin and its receptor (and other related receptors) that have a broad, complex mechanism of interaction, we have very little definitive information on how calcitonin interfaces with its receptor to signal to target cells. The current project utilises a novel method of permanently linking calcitonin to its receptor, allowing identification of how the two components come together. This information provides important fundamentals for understanding how this and related receptors work and the potential for rational design of improved therapeutic tools.Read moreRead less
Cleavage Methods Of Mutation Detection: Improvement And Application In Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,044,349.00
Summary
Genes contain the information to build our body and keep it operating normally. These genes are inherited from our parents and number around 100,000. Faults in these genes can cause inherited diseases such as cystic fibrosis, cancers and common disorders such as Asthma and diabetes. These genes need detecting so that particular genes can be identified as causing the disease and also so that patients can have their disease properly diagnosed so that proper therapy and information can be given to ....Genes contain the information to build our body and keep it operating normally. These genes are inherited from our parents and number around 100,000. Faults in these genes can cause inherited diseases such as cystic fibrosis, cancers and common disorders such as Asthma and diabetes. These genes need detecting so that particular genes can be identified as causing the disease and also so that patients can have their disease properly diagnosed so that proper therapy and information can be given to the patients. In future similar changes (but changes not causing disease) may be searched for in patients to overcome the side effects of drugs. Our centre specializes in the methods of detecting faults and their application. Two of our methods are being used around the world and one is being sold as simple kit. These methods still have drawbacks and the work proposed is to overcome some of these. We propose to apply our and other methods to faults in genes which have recently been shown to cause diseases of the artery. This is an exciting new development that shows that this disease is similar to cancer. We are fortunate to have attracted Dr Paula Bray from the laboratory which discovered this. This new finding needs to be studied in more detail and may identify life-style factors which cause coronary heart disease. Our studies will also assist in gene therapy when it becomes available.Read moreRead less
I am a scientist aiming to improve health outcomes by facilitating the collection and unification of data on human genetic variation together with its clinical impact on human health.