Benchmarking the neurophysiology of human cortex models in vitro. This project aims to improve human brain models in vitro by developing an analytical tool benchmarking biophysical similarities to the adult human cortex. This project expects to generate new knowledge by testing for the first time the theory that integrating sensory-like inputs and awake/sleep-like cycles of electrical activity in vitro may complete the maturation of human brain organoid models. It will also generate new methods ....Benchmarking the neurophysiology of human cortex models in vitro. This project aims to improve human brain models in vitro by developing an analytical tool benchmarking biophysical similarities to the adult human cortex. This project expects to generate new knowledge by testing for the first time the theory that integrating sensory-like inputs and awake/sleep-like cycles of electrical activity in vitro may complete the maturation of human brain organoid models. It will also generate new methods to simplify the analysis of multimodal path-clamping data (Patch-seq). Expected outcomes will facilitate research collaboration and the reproducibility of accurate experimental replicates of the human brain. This will provide significant benefits in the global race to understand human brain computation mechanisms.Read moreRead less
EGF Peptide Signalling Improves Oocyte Maturation And Quality
Funder
National Health and Medical Research Council
Funding Amount
$586,891.00
Summary
Infertility is common and although IVF is widely accepted, the procedure is expensive and is associated with health risks. Using laboratory animals, we have developed significant new insights into mechanisms regulating egg quality. These insights have allowed us to develop a new approach to infertility treatment - crucially, one that eliminates the need for ovarian hormone therapy used in IVF. This project will investigate the basic mechanisms underlying our new approach to enable safe clinical ....Infertility is common and although IVF is widely accepted, the procedure is expensive and is associated with health risks. Using laboratory animals, we have developed significant new insights into mechanisms regulating egg quality. These insights have allowed us to develop a new approach to infertility treatment - crucially, one that eliminates the need for ovarian hormone therapy used in IVF. This project will investigate the basic mechanisms underlying our new approach to enable safe clinical implementation.Read moreRead less
Impaired Bone Remodelling Leads To Failure Of Orthopaedic Prostheses
Funder
National Health and Medical Research Council
Funding Amount
$515,917.00
Summary
The failure of bone prostheses is becoming a major health problem. More than 26,000 hip, and an equal number of knee, replacements were performed in Australia in 2002 with the number increasing between 5%-10% each year for the previous 10 years. Disturbingly, the incidence of revision hip surgery in Australia is now more than 15%, meaning that, despite the impressive success of joint replacement surgery, a significant number of arthroplasties fail. It is becoming more common for young, active in ....The failure of bone prostheses is becoming a major health problem. More than 26,000 hip, and an equal number of knee, replacements were performed in Australia in 2002 with the number increasing between 5%-10% each year for the previous 10 years. Disturbingly, the incidence of revision hip surgery in Australia is now more than 15%, meaning that, despite the impressive success of joint replacement surgery, a significant number of arthroplasties fail. It is becoming more common for young, active individuals to receive joint replacement surgery to improve their quality of life. This, combined with increasing life expectancy, and the known higher rate of failure of joint replacements in younger patients, means that the morbidity of a failed replacement, and the mobidity and associated mortality of revision surgery, will become an increasingly important health issue, with a major impact upon health budgets. The overwhelming majority of hip and knee prostheses have metal or ceramic on polyethylene bearing surfaces. It is now apparent that most implants fail due to bone loss around them leading to loosening, and evidence is accumulating that polyethylene wear particles are a major contributing factor to this process. It is therefore vital that we obtain better understanding of the causes of implant failure in order to extend the life of these implants and this project is designed to do so.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989226
Funder
Australian Research Council
Funding Amount
$340,000.00
Summary
Multi-photon imaging for infection, immunity, and self recognition. This proposal will address a gap in our imaging capabilities, allowing us to visualise the movement of immune cells and infectious agents such as bacteria and viruses within living tissues. This will immensely improve our capacity to understand interactions between the immune system, invading organisms and the rest of our body. The intravital imaging system will provide novel insights into how the immune system works, which will ....Multi-photon imaging for infection, immunity, and self recognition. This proposal will address a gap in our imaging capabilities, allowing us to visualise the movement of immune cells and infectious agents such as bacteria and viruses within living tissues. This will immensely improve our capacity to understand interactions between the immune system, invading organisms and the rest of our body. The intravital imaging system will provide novel insights into how the immune system works, which will benefit the design of vaccines, the treatment of cancer, and our understanding of allergy. This state-of-the-art facility will also provide vital training in an emerging technology that will have application in many areas of biology.
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Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100037
Funder
Australian Research Council
Funding Amount
$170,000.00
Summary
Laser microdissection facility. Laser microdissection facility: Laser microdissection (LMD) is a proven and effective approach to isolate pure cell populations from heterogeneous tissue samples in order to analyse DNA, RNA, and protein content. LMD provides an important advantage to research engaged in basic biological research as it allows for molecular profiling at the cellular level that can not be achieved from whole tissue samples. This project will provide a LMD facility aimed at understan ....Laser microdissection facility. Laser microdissection facility: Laser microdissection (LMD) is a proven and effective approach to isolate pure cell populations from heterogeneous tissue samples in order to analyse DNA, RNA, and protein content. LMD provides an important advantage to research engaged in basic biological research as it allows for molecular profiling at the cellular level that can not be achieved from whole tissue samples. This project will provide a LMD facility aimed at understanding many important biologically cellular mechanisms.Read moreRead less
Identifying novel roles of disease-related proteins in the regulation of exocytosis and nervous communication. This research aims to identify new molecules involved in regulating nerve communication and hormone secretion and which are relevent to human diseases and conditions including Type 2 Diabetes, Down Syndrome, Alzheimer's Disease and Huntington's Disease. The findings may provide new targets in the treatments of such conditions. This research is therefore of special relevance to National ....Identifying novel roles of disease-related proteins in the regulation of exocytosis and nervous communication. This research aims to identify new molecules involved in regulating nerve communication and hormone secretion and which are relevent to human diseases and conditions including Type 2 Diabetes, Down Syndrome, Alzheimer's Disease and Huntington's Disease. The findings may provide new targets in the treatments of such conditions. This research is therefore of special relevance to National Research Priority 2: Promoting and Maintaining Good Health and especially to the sub-areas of this Research Priority 2: Ageing well, ageing productively and Preventative healthcare.Read moreRead less
Synthesis of substrate analogues for probing catalytic mechanisms and specificity of enzymes involved in the metabolism of plant polysaccharides. The project is aimed at strengthening collaborations between research groups in Adelaide and France, with the specific objective of synthesizing substrate analogues as probes of enzymatic mechanisms and substrate specificity in polysaccharide hydrolases and synthases of barley. The chemical expertise resides in France, while the enzymatic work will be ....Synthesis of substrate analogues for probing catalytic mechanisms and specificity of enzymes involved in the metabolism of plant polysaccharides. The project is aimed at strengthening collaborations between research groups in Adelaide and France, with the specific objective of synthesizing substrate analogues as probes of enzymatic mechanisms and substrate specificity in polysaccharide hydrolases and synthases of barley. The chemical expertise resides in France, while the enzymatic work will be conducted largely in Australia. Exchange of research staff, particularly at the postgraduate student and research associate levels, is considered essential to capture the benefits of the complementary expertise and to extend an existing international collaboration. The target enzymes are of central importance in cell wall metabolism during development of higher plants.Read moreRead less
Human Leukocyte Antigen-A and -B regulation of Natural Killer cell function. The aim of this project is to determine how genetic variation in the genes encoding cell surface receptors expressed by innate lymphocytes and the molecules they recognise diversifies their capacity to sense and respond to infection. This knowledge is critical for understanding why there are intrinsic differences between individuals with respect to their capacity to respond to different types of infection and will ultim ....Human Leukocyte Antigen-A and -B regulation of Natural Killer cell function. The aim of this project is to determine how genetic variation in the genes encoding cell surface receptors expressed by innate lymphocytes and the molecules they recognise diversifies their capacity to sense and respond to infection. This knowledge is critical for understanding why there are intrinsic differences between individuals with respect to their capacity to respond to different types of infection and will ultimately inform our capacity to better deploy personalised medicines.Read moreRead less
Molecular mechanisms of catalysis and the basis of substrate specificity in polysaccharide hydrolases. Reaction intermediates along hydrolytic pathways and molecular determinants of substrate specificity of barley B-glucan exo- and endohydrolases will be defined using crystallographic and kinetic analyses. These enzymes are of central importance in cell wall metabolism during development of higher plants, and in plant-pathogen interactions. Realization of the project objectives will not only pro ....Molecular mechanisms of catalysis and the basis of substrate specificity in polysaccharide hydrolases. Reaction intermediates along hydrolytic pathways and molecular determinants of substrate specificity of barley B-glucan exo- and endohydrolases will be defined using crystallographic and kinetic analyses. These enzymes are of central importance in cell wall metabolism during development of higher plants, and in plant-pathogen interactions. Realization of the project objectives will not only provide fundamental information on catalytic mechanisms, but will also provide opportunities to manipulate enzyme specificity. Further, site-directed mutagenesis of the enzymes will be used to generate glycosynthases, which will be evaluated for their ability to synthesise novel oligosaccharide and polysaccharide products, some of which might show immunomodulating activity.Read moreRead less
Improving and manipulating the immune adjuvant properties of recombinant fowlpox vectors. Unbalanced immune responses may cause or worsen common and important diseases such as infections, allergies, cancers and autoimmunity. Interleukin-4 (IL-4) is the only immune active product or cytokine that safely skews an aberrant immune response to a healing type of response. Fowlpox viruses (FPV) provide safe and effective human vaccines. Engineering FPV to make both a relevant antigen and a cytokine is ....Improving and manipulating the immune adjuvant properties of recombinant fowlpox vectors. Unbalanced immune responses may cause or worsen common and important diseases such as infections, allergies, cancers and autoimmunity. Interleukin-4 (IL-4) is the only immune active product or cytokine that safely skews an aberrant immune response to a healing type of response. Fowlpox viruses (FPV) provide safe and effective human vaccines. Engineering FPV to make both a relevant antigen and a cytokine is proprietary technology. With our commercial partner and using experimental mice, we will test the concept that FPV making a model antigen and IL-4 initiate and/or maintain beneficial Type 2 responses. A successful outcome will guide clinical FPV-based vaccine development for the treatment of important human and veterinary diseases.Read moreRead less