Novel human tryptases: their potential role in inflammatory diseases of the young and old. We have discovered a number of novel human tryptases, and while other members of this enzyme family have been implicated in the development of inflammatory diseases (including rheumatoid arthritis), little is known about these new molecules. We aim to characterise these new enzymes by determining what part of the body they are produced in, whether they are associated with specific inflammatory diseases, an ....Novel human tryptases: their potential role in inflammatory diseases of the young and old. We have discovered a number of novel human tryptases, and while other members of this enzyme family have been implicated in the development of inflammatory diseases (including rheumatoid arthritis), little is known about these new molecules. We aim to characterise these new enzymes by determining what part of the body they are produced in, whether they are associated with specific inflammatory diseases, and what target molecules they act on. A better understanding of these factors will increase the chances of finding cures and developing better treatments for important inflammatory diseases of the ageing population.Read moreRead less
Transcriptional Regulation Of The Complement Receptor 2 Gene (CR2/CD21) During B Cell Lineage Committment
Funder
National Health and Medical Research Council
Funding Amount
$466,500.00
Summary
The complement system is a very important pathway within the human immune system. One of the receptors within this system is complement receptor 2 or CR2. CR2 has not only been shown to be important within the inflammatory response and defence against microbes but is also important in normal generation of a B cell immune response . B cells not only produce antibodies against foreign organisms but in some cases dysfunction of the B cell can bring about autoimmunity by production of antibodies aga ....The complement system is a very important pathway within the human immune system. One of the receptors within this system is complement receptor 2 or CR2. CR2 has not only been shown to be important within the inflammatory response and defence against microbes but is also important in normal generation of a B cell immune response . B cells not only produce antibodies against foreign organisms but in some cases dysfunction of the B cell can bring about autoimmunity by production of antibodies against self tissues and cells . How the CR2 gene turns on expression on different cells within the immune system is complex. The amount of receptor on the surface of antibody producing B cells has important implications to B cell biology. As CR2 expression is turned on at an important point within the antibody producing B cell and the levels of this receptor can influence B cell function, understanding how this gene is regulated is important.Read moreRead less
Versatile elastin based hybrid hydrogels for chondrocyte transplantation and repair. Cartilage repair is often limited after significant trauma, sports injury and disease. This project will generate a new family of hybrid biomaterials constructed by precisely blending natural and synthetic components. These novel biomaterials will establish the foundation for manufactured prefabrication and in situ injection to promote healing.
Cells must regulate the flow of ions and water across their membranes in order to survive and function normally. The balance of ions and water is controlled by ion channels - proteins that control the permeability of the cell membrane. Of the ion channels, chloride channels are the most abundant in cells. They are central to the functioning of normal cells as well as playing a key role in many disease states. Our group was the first to identify and characterise a new class of chloride channel wh ....Cells must regulate the flow of ions and water across their membranes in order to survive and function normally. The balance of ions and water is controlled by ion channels - proteins that control the permeability of the cell membrane. Of the ion channels, chloride channels are the most abundant in cells. They are central to the functioning of normal cells as well as playing a key role in many disease states. Our group was the first to identify and characterise a new class of chloride channel which plays a key roles in the regulation of the immune system. These channels are unusual in that they can move between two states: a soluble state and a state that resides in the cell membrane. We have determined the first structures of this class of channel in both the soluble state and what is believed to be the membrane docking state. This has given us the first atomic picture of how this channel protein can alter its structure so as to carry out its function. In this project, we will determine: how the protein completes the transition into the membrane state; the structures of other key members of this class of channel protein; complexes between channel proteins and other cellular proteins; and the structure of the protein in the membrane state. We will also determine how several drugs control the activity of this channel. The results of our work will have specific implications for our channel and will serve as a paradigm other members of this new class of chloride channel. Understanding how this channel functions and how the current drugs control it will lead to the development of a new class of therapeutic agents that will control these channels by preventing the transition from the soluble to the membrane state.Read moreRead less
The role of heparan sulfate proteoglycans in the control of osteoblast phenotype. Very little is known about how bone cells progress from a naive precursor state, through differentiation and then maturation into adult cells. We wish to purify sugars from the bone cell membrane, extracellular matrix and culture medium, and examine the cellular response following the addition of these various sugar fractions to osteoblast cell cultures in combination with known growth factors. If we can control ....The role of heparan sulfate proteoglycans in the control of osteoblast phenotype. Very little is known about how bone cells progress from a naive precursor state, through differentiation and then maturation into adult cells. We wish to purify sugars from the bone cell membrane, extracellular matrix and culture medium, and examine the cellular response following the addition of these various sugar fractions to osteoblast cell cultures in combination with known growth factors. If we can control the progression of osteoblastic cells through the phases of recruitment, proliferation, differentiation and maturation by the addition of specific sugar fractions then we can potentially control bone formation.Read moreRead less
Structure-based design of anti-osteoporotic drug leads: an integrated approach. One of the major consequences of Australia's aging population is that age-related diseases, such as osteoporosis, are increasing. Apart from the significant human suffering caused by this disease, there is an immense financial burden on the community, patients and their families. Current treatments for osteoporosis are often ineffective and also have major side-effects. An enzyme has been identified which plays a cru ....Structure-based design of anti-osteoporotic drug leads: an integrated approach. One of the major consequences of Australia's aging population is that age-related diseases, such as osteoporosis, are increasing. Apart from the significant human suffering caused by this disease, there is an immense financial burden on the community, patients and their families. Current treatments for osteoporosis are often ineffective and also have major side-effects. An enzyme has been identified which plays a crucial role in the progression of this disease by increasing the rate of bone-thinning. We will make compounds to slow down this enzyme. This project will provide the basis for the future development of new and improved drugs to treat osteoporosis.Read moreRead less
Novel Glycoproteomic based diagnostic technology for identifying cartilage tissue turnover and repair. Osteoarthritis is a long-term debilitating disease, which results in the loss of cartilage in the joints, leading to pain and disability. This is a major problem and cost in ageing societies, yet the mechanisms of joint deterioration are still poorly understood. This project will investigate proteoglycans and proteoglycan fragments produced by cells of the joint, detailing the structure of th ....Novel Glycoproteomic based diagnostic technology for identifying cartilage tissue turnover and repair. Osteoarthritis is a long-term debilitating disease, which results in the loss of cartilage in the joints, leading to pain and disability. This is a major problem and cost in ageing societies, yet the mechanisms of joint deterioration are still poorly understood. This project will investigate proteoglycans and proteoglycan fragments produced by cells of the joint, detailing the structure of their sugar components, and map which regions are interacting with antibodies. Understanding these proteoglycan fragments will help us to determine their role in disease progression, and application of this knowledge will assist in the development of an early diagnostic for osteoarthritis.Read moreRead less
Rapid functional analysis of genes involved in skeletal development. Abnormalities of the skeleton are of enormous clinical significance in terms of both number of individuals affected and the cost of treatment. Data derived from this project will underpin targeted research on the mechanisms of inherited and common diseases of cartilage and bone, yielding novel diagnostic and therapeutic targets. In addition, the improved knowledge of cartilage and bone cell development will inform new approache ....Rapid functional analysis of genes involved in skeletal development. Abnormalities of the skeleton are of enormous clinical significance in terms of both number of individuals affected and the cost of treatment. Data derived from this project will underpin targeted research on the mechanisms of inherited and common diseases of cartilage and bone, yielding novel diagnostic and therapeutic targets. In addition, the improved knowledge of cartilage and bone cell development will inform new approaches for developing stem cell therapies and the production of novel biomaterials for the repair of bones and joints. The outcomes of this study will therefore benefit the full spectrum of society from infants to the aged.Read moreRead less