Major Xenoantigens For Neovascularised Porcine Xenografts: The Role Of PERV And MHC In Rejection And Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$504,750.00
Summary
Cross-species transplants (xenografts) of pig organs which use donor pig blood vessels are rejected by antibody which recognises a special target (xenoantigen) on the pig blood vessels; other pig tissue transplants (cellular transplants) which use recipient (not donor pig) blood vessels, are rejected by white blood cells called CD4 T cells. The pig targets recognised by the xenoreactive CD4 T cells are unknown. We plan to identify the major target(s) involved in cellular xenograft rejection. Thi ....Cross-species transplants (xenografts) of pig organs which use donor pig blood vessels are rejected by antibody which recognises a special target (xenoantigen) on the pig blood vessels; other pig tissue transplants (cellular transplants) which use recipient (not donor pig) blood vessels, are rejected by white blood cells called CD4 T cells. The pig targets recognised by the xenoreactive CD4 T cells are unknown. We plan to identify the major target(s) involved in cellular xenograft rejection. This information can then be used to specifically remove or disable only those CD4 T cells capable of recognising the pig tissue and hence facilitate xenograft survival or tolerance without immunosuppression. In this way, the remainder of the CD4 T cell population and immune system is preserved intact. Recent studies have demonstrated that a pig virus (PERV) can be transmitted from pig tissue xenografts to recipient tissues. Our studies have also suggested that the process of xenograft rejection and the immunological recognition of transplant recipient cells infected with the pig virus, are closely related. We plan to investigate this relationship and ascertain whether the immunological destruction of the pig tissue xenograft is largely due to an immune response generated against the pig virus(es) it carries. As an extension of this concept, we will investigate whether long-term xenograft survival (tolerance) is associated with lack of immune reactivity to the pig virus and hence a continual capacity for pig virus to be transmitted to host tissues. This outcome could result in the development of unwanted disease(s) in transplant patients. To prevent these problems, our studies will determine whether it will be essential for such pig virus to be eliminated from the donor pig tissue before transplantation, e.g. by the development of potent anti-viral agents and-or via the development of pig herds that have been genetically engineered to be pig virus (PERV)-deficient.Read moreRead less
AusCAN Risk Assessment For Sitting Acquired Pressure Ulcers
Funder
National Health and Medical Research Council
Funding Amount
$1,707,297.00
Summary
Sitting acquired pressure ulcers are one of the major complications that occur after spinal cord injury. This project will determine factors that are associated with the development of sitting acquired pressure ulcers after spinal cord injury; and will develop a risk assessment tool that can identify those at high risk of pressure ulcer development. The cost of treating a pressure ulcer will also be assessed. This will enable cost-effective preventive treatment to be used in these individuals.
Periodontal Mesenchymal Stem Cells For Periodontal Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$358,000.00
Summary
Dental diseases affecting the gums (periodontal disease) are extremely prevalent in our society. The effects of periodontal disease can be particularly severe as loss of support for the teeth leads to loose teeth and severely compromised masticatory function. If left untreated, the associated pain and loss of function may necessitate extraction of the teeth. We have recently identified cells residing in the periodontal ligament which may be adult stem cells. This project will further characteriz ....Dental diseases affecting the gums (periodontal disease) are extremely prevalent in our society. The effects of periodontal disease can be particularly severe as loss of support for the teeth leads to loose teeth and severely compromised masticatory function. If left untreated, the associated pain and loss of function may necessitate extraction of the teeth. We have recently identified cells residing in the periodontal ligament which may be adult stem cells. This project will further characterize these cells and explore whether they can be used to restore periodontal tissues damaged by periodontal disease.Read moreRead less
Opioid Actions On Sensory Neuron Excitability In Vitro
Funder
National Health and Medical Research Council
Funding Amount
$241,018.00
Summary
Morphine and related drugs are very widely used for pain relief, although the way they affect the pain-sensitive cells in the body is not well understood. Use of morphine for extended periods of time often makes morphine less effective for pain relief, which makes it necessary to increase the dose of morphine given. This leads to an increase in the unwanted side effects of morphine, and can eventually lead to morphine becoming ineffective in controlling pain. This study is designed to examine ho ....Morphine and related drugs are very widely used for pain relief, although the way they affect the pain-sensitive cells in the body is not well understood. Use of morphine for extended periods of time often makes morphine less effective for pain relief, which makes it necessary to increase the dose of morphine given. This leads to an increase in the unwanted side effects of morphine, and can eventually lead to morphine becoming ineffective in controlling pain. This study is designed to examine how morphine affects pain-sensitive cells, and to determine how continued use of morphine changes the way pain-sensitive cells respond to morphine. We hope that by understanding how morphine works on pain-sensitive cells, we can understand why it does not work so well after continued use. This information should enable us to design better forms of pain relief than we have now.Read moreRead less
Cellular And Molecular Events During Antigen Dependent B Cell Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$283,329.00
Summary
The immune system is essential for protecting us against invasion from without by viruses and bacteria and invasion from within by cancer cells. Among the white blood cells making up this system are those responsible for producing antibodies. To ensure that all possible infections and tumours can be recognised, the body needs to manufacture a very large number of these cells on a continuous basis. The aim of this project is to work out the mechanism responsible for controlling their production a ....The immune system is essential for protecting us against invasion from without by viruses and bacteria and invasion from within by cancer cells. Among the white blood cells making up this system are those responsible for producing antibodies. To ensure that all possible infections and tumours can be recognised, the body needs to manufacture a very large number of these cells on a continuous basis. The aim of this project is to work out the mechanism responsible for controlling their production and function using a novel experimental system. By pinpointing the different stages involved in antibody production in the normal host we should be in a better position to make longer lasting vaccines in the future and to understand what goes wrong with these white cells in disease. In particular, the results should shed light on the chronic form of leukaemia called myeloma and some of the autoimmune disorders like the rheumatic diseases which occur when the antibodies being produced attack our own tissues.Read moreRead less
Deciphering The Metabolic And Endocrine Profile Of Healthy Adipocytes
Funder
National Health and Medical Research Council
Funding Amount
$563,194.00
Summary
Obesity is associated with the development of metabolic diseases, however, it is becoming clear that it is where the excess fat is stored that is more important when predicting the health risks associated with obesity. This project aims to identify whether adipocyte progenitor cells, which eventually become fat cells, are ‘preprogrammed’ and whether differences in these cells explain the generation of either healthy or unhealthy fat in different locations of the body.
To Repair An Osteo-chondral Defect In An Experimental Rabbit Model Using A Structured 3D Nano-composite Scaffold Loaded With Mesenchymal Stem Cells (MSC)
Funder
National Health and Medical Research Council
Funding Amount
$92,314.00
Summary
The treatment of cartilage damage is a major problem in orthopaedic practice. The use of a 3D scaffold may overcome many challenges associated with cartilage and bone repair and regeneration. The aim of this research is to culture bone and cartilage cells into a prefabricated scaffold which may then be tested in an animal model. The results of this research may offer a new method of treating post-traumatic and osteoarthritic defects.
Opioid Actions On Identified Sensory Neurons In Vitro
Funder
National Health and Medical Research Council
Funding Amount
$371,850.00
Summary
Opioids (in particular morphine) are the gold standard drugs for the relief of most types of moderate to severe pain. Despite the effectiveness of opioids and other analgesics, many people still suffer unrelieved pain. There are 2 main reasons for this. Firstly, there are some types of pain that are refractory to currently used analgesics from the outset, and secondly, chronic conditions may require escalating doses of analgesics for adequate pain relief, and these does may increase until side e ....Opioids (in particular morphine) are the gold standard drugs for the relief of most types of moderate to severe pain. Despite the effectiveness of opioids and other analgesics, many people still suffer unrelieved pain. There are 2 main reasons for this. Firstly, there are some types of pain that are refractory to currently used analgesics from the outset, and secondly, chronic conditions may require escalating doses of analgesics for adequate pain relief, and these does may increase until side effects become intolerable. My studies will provide insight into the reasons that underlie the differential effectiveness of opioids in acute pain conditions, as well as the reasons why opioids lose their effectiveness over time. These studies will also identify molecular targets that may be important for developing analgesics for specific pain conditions. Because the head is the source of many familiar painful conditions, including tooth pain, migraine and temporomandibular disorders, I will be using neurons from the trigeminal ganglion, the part of the nervous system which supplies the sensory innervation to the structures involved in these pain states. By using mice as experimental animals, I will be able to investigate the contribution of neurons that innervate specific parts of the head to these pain states, and study how chronic morphine treatment affects the behavior of these cells. I hope that these studies will provide a basis for designing strategies that improve the effectiveness of existing analgesics, and perhaps lead to the identification of new, better pain relievers.Read moreRead less