Structural And Functional Properties Of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) Isoforms
Funder
National Health and Medical Research Council
Funding Amount
$188,623.00
Summary
Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1-CD31) is a member of the Ig-superfamily that is implicated in a variety of biological responses such as leukocyte transmigration, angiogenesis, cellular signaling, cell adhesion and migration. Recent studies from this laboratory has demonstrated that PECAM-1 contains intracytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIM) that upon phosphorylation can mediate an inhibitory function through recruitment and activation of protei ....Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1-CD31) is a member of the Ig-superfamily that is implicated in a variety of biological responses such as leukocyte transmigration, angiogenesis, cellular signaling, cell adhesion and migration. Recent studies from this laboratory has demonstrated that PECAM-1 contains intracytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIM) that upon phosphorylation can mediate an inhibitory function through recruitment and activation of protein tyrosine phosphatases, SHP-1 and SHP-2. We would therefore consider PECAM-1 as a new member of an emerging Ig-ITIM superfamily. Members of the Ig-ITIM gene family have both inhibitory-non-inhibitory receptors which upon ligation of specific receptors can globally stimulate or inhibit cellular activation in the context of B cells, Tcells, mast cells , endothelial cells or platelets. Balancing the threshold of cellular activation is critical in the immune response to tumours, pathogens or allergens, to arrest autoimmune and infectious disease, to provoke immunological memory from vaccination and to dampen the extent and duration of platelet activation. Our investigations are focussing on the isolation and functional characterisation of PECAM-1 family members to define their role in regulating cell signaling pathways in vascular and haematopoietic cells. We predict that PECAM-1 has numerous undefined family members that exist as multiple isoforms as a product of separate genes, alternative splicing of discrete exons and single point mutations giving rise to conservative and non-conversative amino acid changes. The longer term potential of this study is to provide knowledge for understanding the structural and functional roles of PECAM-1 isoforms in physiological cells in health and disease. This knowledge could then be applied to provide targets for novel therapeutic interventions in the clinical management of autoimmune disease, humoral and inflammatory responses.Read moreRead less
Peripheral Neuropathy And Pain: Role Of The Sphingosine Kinase-sphingosine 1-phosphate System
Funder
National Health and Medical Research Council
Funding Amount
$282,905.00
Summary
Understanding the neural mechanisms that generate pathological pain remains one of the essential goals for the development of effective treatments for pain, chronic pain with less side effects. Lipids are able to modulate pain perception. We will determine the role of a molecule named sphingosine 1-phosphate as a basis for the development of therapies for the treatment of neuropathic pain.
Defining Vascular Health And Modifiable Risk Factors Over Time In Childhood.
Funder
National Health and Medical Research Council
Funding Amount
$368,061.00
Summary
Adult heart disease and strokes have their origin in childhood. We will follow healthy children and children with diabetes or obesity over 2 years during puberty when blood vessel disease is detectable. We will define which are the most sensitive markers of blood vessel disease and the continuum of risk factors. This is essential knowledge to best define children at risk and to test clinical and public health interventions.
Apoptotic Pathways In Pancreatic Beta Cells Leading To Type 1 Diabetes And Transplant Rejection
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
The destruction of insulin-producing beta cells in the pancreas by immune cells leads to the need for daily insulin injections in patients with type 1 diabetes. This project aims to understand how beta cells are destroyed. A knowledge of the process by which this occurs will indicate ways we can protect these cells. Our previous work has suggested strategies that may protect beta cells, and we aim to test these. Such protection may eventually allow beta cell replacement by transplantation.
Evaluation Of Multidisciplinary Care Plans For Patients With Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$83,500.00
Summary
Care planning for patients with chronic illnesses and complex needs is a major part of the Commonwealth Enhanced Primary Care package. This initiative, announced in late 1999, provides access to Medicare Benefits Schedule (MBS) items to remunerate general practitioners, involved in developing multidisciplinary care plans in cooperation with other health care providers. An issue of importance, and the one that this project investigates, is whether disease specific care is addressed in care plans ....Care planning for patients with chronic illnesses and complex needs is a major part of the Commonwealth Enhanced Primary Care package. This initiative, announced in late 1999, provides access to Medicare Benefits Schedule (MBS) items to remunerate general practitioners, involved in developing multidisciplinary care plans in cooperation with other health care providers. An issue of importance, and the one that this project investigates, is whether disease specific care is addressed in care plans and whether the care planning process is associated with improved provision and outcomes of care for a specific chronic illness. The chronic illness that has been chosen for this research project is diabetes because of its prevalence in the community, importance in general practice and because there are accepted standards of process and outcomes of care against which diabetes care contained in EPC care plans can be bench marked. Diabetes is estimated to affect 7.5% of the adult Australian population with more than 85% of those affected having type 2 or mature onset diabetes. Increasingly care of type 2 diabetes is provided in primary care under share care arrangements with specialist diabetes services and in a multidisciplinary team approach involving the patient and their carer as well as relevant health professionals. A recent review has shown that there is a lack of evidence on whether multidisciplinary care is associated with improved process and outcomes of diabetes care. The project will involve 50 general practitioners and 200 of their patients with diabetes in South West Sydney. The design of the project involves audit of the care plans to examine the extent and quality of the diabetes care contained in comparison to accepted benchmarks. The project will also audit the patients' medical records for the year of care before and after the care plan. This care will be compared to published guidelines for process of care and goals for outcomes.Read moreRead less
Viral Triggers Of Autoimmunity And Type 1 Diabetes: A Prospective Study Of At Risk Children
Funder
National Health and Medical Research Council
Funding Amount
$475,106.00
Summary
We are studying the role of viruses in causing type 1 (insulin dependent) diabetes. By following babies from birth, we can see whether early signs of damage to the body's insulin producing cells results from infection with particular viruses. We will study the genes and other features of these viruses to help us understand why they cause diabetes, and how they relate to other factors such as diet and vitamin D. The results may provide valuable information for the future prevention of diabetes.