Determination Of Irradiation Dose Efficacy For Use In Impaction Grafting At Revision Joint Replacement
Funder
National Health and Medical Research Council
Funding Amount
$411,517.00
Summary
Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence ....Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence of early complications of this procedure have included loss of fixation within the bone. Fracture of the bone around prostheses has also reported in some centres. These events require more surgery, putting the patient at higher risk greater complications and longer rehabilitations. Recent improvements in surgical technique and donor bone preparation have improved results. A current debate questions whether the dose of irradiation can be reduced from 25 kGy, while maintaining sterility of allografts. The risk of bacterial contamination in allografts is low, and irradiation reduces the mechanical strength of the graft, contributing to complications when irradiated bone is used. The benefits of decontaminating the bone may be outweighed by the higher risk for failure due to poor bone quality and resulting prosthesis instability. We will use ISO standards to test the validity of radiation dose for sterilising bone ex vivo. In the absence of controlled human studies, our aim is also to compare the results of impaction grafting with non-irradiated bone versus bone irradiated at current doses used by Australian bone banks, and lower doses indicated by ex vivo testing. We will use a large animal model of revision hip replacement, with precise measures of prosthesis stability. The results of this study will guide clinical decisions regarding the efficacy of current bone graft preparation procedures and the use of irradiated bone in human hip replacement surgery.Read moreRead less
Exploring the immunomodulatory potential of Natural Killer T cells. Natural Killer T cells (NKT cells) are an innate-like population of T cells that recognise a range of lipid based antigens when bound to the antigen-presenting molecule, CD1d. Once activated, NKT cells rapidly secrete a variety of cytokines. This project, in partnership with Vaxine Pty Ltd, aims to gain a basic understanding of NKT recognition of lipids and NKT cell activation by lipids. The project aims to use a combination of ....Exploring the immunomodulatory potential of Natural Killer T cells. Natural Killer T cells (NKT cells) are an innate-like population of T cells that recognise a range of lipid based antigens when bound to the antigen-presenting molecule, CD1d. Once activated, NKT cells rapidly secrete a variety of cytokines. This project, in partnership with Vaxine Pty Ltd, aims to gain a basic understanding of NKT recognition of lipids and NKT cell activation by lipids. The project aims to use a combination of cellular immunology and structural biology to gain insight into NKT cell agonism.Read moreRead less
Enhanced multivalent vaccine responses using a novel vaccine vector system. Enhanced multivalent vaccine responses using a novel vaccine vector system. This project aims to develop a multicomponent vaccine system to deliver equal effectiveness against several disease targets in a single administration. New and innovative vaccine design strategies incorporating economical commercial production processes are urgently needed for new and existing human and animal health applications. A vaccine capab ....Enhanced multivalent vaccine responses using a novel vaccine vector system. Enhanced multivalent vaccine responses using a novel vaccine vector system. This project aims to develop a multicomponent vaccine system to deliver equal effectiveness against several disease targets in a single administration. New and innovative vaccine design strategies incorporating economical commercial production processes are urgently needed for new and existing human and animal health applications. A vaccine capable of targeting multiple diseases by a single injection is an obvious way to expedite future vaccine development and deployment. However, the recipient’s immune system can repress equivalent responses to these multicomponent vaccines. This project’s research is expected to address these problems, and underpin the future commercial development of this vaccine platform.Read moreRead less
The development of a potent new passive immunotherapeutic for the treatment and prevention of bacterial sepsis and septic shock. Bacterial sepsis and septic shock is a leading cause of death in hospital intensive care units and represents a significant public health burden. By developing a new passive immunotherapeutic regimen to treat and prevent bacterial sepsis and septic shock, the project aims to reverse the significant mortality and morbidity associated with this condition.
Understanding The Role Of The Atypical Cadherin Fat4 In Lymphatic Vascular Development
Funder
National Health and Medical Research Council
Funding Amount
$1,006,248.00
Summary
This application will define the role of a large cell adhesion molecule, FAT4, in lymphatic vascular development. By understanding how FAT4 functions in lymphatic vessels, we will gain insight to the mechanisms by which mutations in the gene that encodes this protein cause a human lymphoedema syndrome.
Male-female Sperm Signalling - A Novel Pathway For Peri-conceptual Health?
Funder
National Health and Medical Research Council
Funding Amount
$674,920.00
Summary
This project will investigate a new biological process in reproduction, whereby sperm delivered to the cervix at coitus transmit signalling molecules called microRNAs that influence the female immune response, to increase the chances of conception and pregnancy. We will define the molecular details of this signalling pathway in mouse models, and then determine whether human sperm have a comparable function in ‘priming’ the female body to conceive.
Signaling in the crypt: a novel metabolic pathway in intestinal stem cells. The gut is the most rapidly renewing tissue in the body, driven by a highly active stem cell niche. Bile acids are emerging as critical regulators of this stem cell niche and disruption of bile acid homeostasis has profoundly adverse effects on intestinal renewal and hence gut health. We are addressing a critical gap in our understanding of how bile acids are controlled within stem cell niche. The aim of the project is ....Signaling in the crypt: a novel metabolic pathway in intestinal stem cells. The gut is the most rapidly renewing tissue in the body, driven by a highly active stem cell niche. Bile acids are emerging as critical regulators of this stem cell niche and disruption of bile acid homeostasis has profoundly adverse effects on intestinal renewal and hence gut health. We are addressing a critical gap in our understanding of how bile acids are controlled within stem cell niche. The aim of the project is to define the critical role of a novel enzyme called UGT8 in controlling intestinal stem cell response to bile acids; this is achieved by modulating UGT8 activity in intestinal stem cell models and determining the effects on stem cell function and the key signalling pathways that control intestinal homeostasis and renewal.Read moreRead less
Use of mitochondrial electron transport chain mutants to evaluate how non-phosphorylating respiration influences plant metabolite profiles and stress tolerance. This project uses transgenic plant technology to elucidate how mitochondrial function impacts on the profile of metabolites in plant cell and tissues and whether altering these profiles influences a plant's ability tog row in harsh conditions. It will contribute to our fundamental knowledge of plant metabolism using a metabolomic anaylsi ....Use of mitochondrial electron transport chain mutants to evaluate how non-phosphorylating respiration influences plant metabolite profiles and stress tolerance. This project uses transgenic plant technology to elucidate how mitochondrial function impacts on the profile of metabolites in plant cell and tissues and whether altering these profiles influences a plant's ability tog row in harsh conditions. It will contribute to our fundamental knowledge of plant metabolism using a metabolomic anaylsis of plant stress response. This will be achieved using new high-throughput technologies, allowing reliable qualitative and quantitative analysis of large numbers of samples. This approach will compliment existing genomic and proteomic analyses of plants exposed to abiotic stress.Read moreRead less
EFR3: Novel gatekeeper of cell proliferation. This interdisciplinary, cross-institutional project uses leading-edge mass spectrometry and the yeast genetic model to enhance knowledge of fundamental signalling mechanisms common to cell proliferation of eukaryotic cells. Building on extensive preliminary data that identifies novel energy-stress control points, this research will generate insights into critical and conserved features of nutrient stress control of cell proliferation that ensures cel ....EFR3: Novel gatekeeper of cell proliferation. This interdisciplinary, cross-institutional project uses leading-edge mass spectrometry and the yeast genetic model to enhance knowledge of fundamental signalling mechanisms common to cell proliferation of eukaryotic cells. Building on extensive preliminary data that identifies novel energy-stress control points, this research will generate insights into critical and conserved features of nutrient stress control of cell proliferation that ensures cell survival. This project advances basic and applied biology. Its outcomes will be relevant to several research areas and industries, specifically to the propagation of cell cultures that nowadays contributes to the production of a myriad of biotechnical and pharmaceutical commodities.
Read moreRead less
Target Of Rapamycin control of nutrient uptake. This project aims to study nutrient uptake in eukaryotes. It is expected to generate new knowledge of critical and conserved features of environmental and Target Of Rapamycin (TOR)-mediated control of nutrient uptake, specifically endocytosis, building on novel preliminary data that identifies novel TOR control points. The expected outcomes include new insights into mechanisms controlling nutrient uptake and fostering institutional collaboration. T ....Target Of Rapamycin control of nutrient uptake. This project aims to study nutrient uptake in eukaryotes. It is expected to generate new knowledge of critical and conserved features of environmental and Target Of Rapamycin (TOR)-mediated control of nutrient uptake, specifically endocytosis, building on novel preliminary data that identifies novel TOR control points. The expected outcomes include new insights into mechanisms controlling nutrient uptake and fostering institutional collaboration. This knowledge is highly relevant to any industry or research project utilising living organisms, as nutrient availability supports survival, cell growth and proliferation.Read moreRead less