Stem cell-based interface tissue engineering. Osteoarthritis (OA) causes extreme pain, disability, and reduced quality of life and overall productivity. It is the musculoskeletal disorder with the greatest social and economic implications internationally, with 9.3% of the adult population projected to suffer from OA by 2030. A tissue engineered product capable of functional repair of ligament-cartilage-bone tissue interfaces will have significant benefits. It will improve patient activity and qu ....Stem cell-based interface tissue engineering. Osteoarthritis (OA) causes extreme pain, disability, and reduced quality of life and overall productivity. It is the musculoskeletal disorder with the greatest social and economic implications internationally, with 9.3% of the adult population projected to suffer from OA by 2030. A tissue engineered product capable of functional repair of ligament-cartilage-bone tissue interfaces will have significant benefits. It will improve patient activity and quality of life, and significantly reduce OA-associated health care costs. This proposal will train a total of 12 new generation researchers in the emergent fields of stem cell biology and tissue engineering, having important benefits for the Australian scientific and industrial communities.Read moreRead less
Why Is The Bone Marrow A “hot-spot” For Myeloma Plasma Cell Metastasis: Are There Gremlins In The System?
Funder
National Health and Medical Research Council
Funding Amount
$651,979.00
Summary
Most cancer patients die because their cancer spreads from a primary site to other tissues in the body. Once escaping the primary site, 70% of all tumours will spread to bone. This raises the question, why is bone a preferred destination for cancer cells? We provide evidence that Gremlin1, made by non-cancer cells within bone, is a key protein that supports cancer growth. This study will examine whether inhibiting Gremlin1 is a potential therapy to inhibit cancer spreading to bone.
Understanding the molecular mechanisms regulating neuronal fusion. Neurons are tightly connected individual cells that communicate through chemical and electrical signals, and this project aims to discover the key molecules that allow these cells to remain as individual units without fusing with each other. The nervous system, unlike other tissues, is made of discrete individual cells, connected by chemical and electrical synapses but not by cytoplasmic continuity. However, how this is achieved ....Understanding the molecular mechanisms regulating neuronal fusion. Neurons are tightly connected individual cells that communicate through chemical and electrical signals, and this project aims to discover the key molecules that allow these cells to remain as individual units without fusing with each other. The nervous system, unlike other tissues, is made of discrete individual cells, connected by chemical and electrical synapses but not by cytoplasmic continuity. However, how this is achieved and how neurons maintain their individuality during development, remodelling and ageing is unknown. The project aims to address this gap using a genetic approach and the nematode Caenorhabditis elegans as an experimental system. The results may provide insights into how the nervous system develops and functions.Read moreRead less
Interactions between phenome and genome at developing CNS synapses during synaptic refinement. Activity-dependent changes in synaptic transmission are vital to development and function of central neuronal networks. However, the critical factors regulating developmental changes in synaptic signals remain largely unknown. We will correlate functional changes in synaptic responses at glutamate-releasing synapses with changes in glutamate receptor composition at a critical period during developmen ....Interactions between phenome and genome at developing CNS synapses during synaptic refinement. Activity-dependent changes in synaptic transmission are vital to development and function of central neuronal networks. However, the critical factors regulating developmental changes in synaptic signals remain largely unknown. We will correlate functional changes in synaptic responses at glutamate-releasing synapses with changes in glutamate receptor composition at a critical period during development, test whether synaptic activation of receptors is required for these changes and define the pattern of activity-dependent changes in gene expression necessary for developmental changes in synaptic transmission. Understanding this interaction between synaptic phenome and activity-dependent genomic expression will expand our understanding of brain development and function.Read moreRead less
Characterisation and improvement of radiation beams used for radiotherapy of small lesions. This project aims to characterise the radiation dose from a medical linear accelerator after the beam has been shaped by a mini-multileaf collimator. The characterisation will be achieved through a combination of computer simulations and experimental investigation of the beam using the technique of three-dimensional gel dosimetry. When the dosage characteristics are known, techniques will be developed to ....Characterisation and improvement of radiation beams used for radiotherapy of small lesions. This project aims to characterise the radiation dose from a medical linear accelerator after the beam has been shaped by a mini-multileaf collimator. The characterisation will be achieved through a combination of computer simulations and experimental investigation of the beam using the technique of three-dimensional gel dosimetry. When the dosage characteristics are known, techniques will be developed to improve radiotherapy treatments in patients with small lesions with sizes of up to a few centimetres. This will lead to an improved outcome for some cancer patients.Read moreRead less
Development of therapeutic agents that target carbonic anhydrase enzymes. This research will discover new chemical entities (compounds) that may lead to therapies for the treatment of cancer, glaucoma and malaria. The research underpins a mechanism to add value to our compounds before partnering with industry to transform the discoveries made here to deliverable therapies that could benefit the health of millions, thus offering a potentially high value contribution to the Australian economy. The ....Development of therapeutic agents that target carbonic anhydrase enzymes. This research will discover new chemical entities (compounds) that may lead to therapies for the treatment of cancer, glaucoma and malaria. The research underpins a mechanism to add value to our compounds before partnering with industry to transform the discoveries made here to deliverable therapies that could benefit the health of millions, thus offering a potentially high value contribution to the Australian economy. The experience and commitment of the multi-disciplinary network of researchers offers exceptional training and employment opportunities for tomorrow's scientists in techniques for discovery and characterisation of novel chemicals, and their interaction with disease targets.Read moreRead less
Levelling the Playing Field: Starting with the School Playground. This project aims to demonstrate the effectiveness of simple, cost-effective programs for changing the way parents and teachers view manageable risk-taking for children with disabilities and increasing the level of responsibility that children take for their own actions. The well-being of all children with disabilities is at risk and the gap continues to widen. New programs, such as the National Disability Insurance Scheme, will p ....Levelling the Playing Field: Starting with the School Playground. This project aims to demonstrate the effectiveness of simple, cost-effective programs for changing the way parents and teachers view manageable risk-taking for children with disabilities and increasing the level of responsibility that children take for their own actions. The well-being of all children with disabilities is at risk and the gap continues to widen. New programs, such as the National Disability Insurance Scheme, will place increasing demands on young people with disabilities. Innovative approaches are desperately. Such programming must begin early, by including children in an age-appropriate ways and simultaneously addressing the issues of adults who have the most significant influence: parents and teachers.Read moreRead less
Hearing, social connectedness, and well-being of ageing adults in Australia. Hearing ability declines with age and hearing loss has a fundamental impact on an adult’s ability to communicate and, in turn, socially connect with others. This benchmark study aims to apply innovative, quantitative and qualitative methods to examine the real-world social connections of adults with hearing loss who use or do not use hearing aids. This project expects to increase understanding of the social impacts of a ....Hearing, social connectedness, and well-being of ageing adults in Australia. Hearing ability declines with age and hearing loss has a fundamental impact on an adult’s ability to communicate and, in turn, socially connect with others. This benchmark study aims to apply innovative, quantitative and qualitative methods to examine the real-world social connections of adults with hearing loss who use or do not use hearing aids. This project expects to increase understanding of the social impacts of age-related hearing loss and the relationship to hearing rehabilitation. The expected outcomes have the potential to guide research, policy, and practice for ageing Australians. This should provide significant benefits, such as reducing social isolation and enhancing the well-being of millions of Australians.Read moreRead less
Development of novel reagents that specifically counteract EphA4 to enhance axonal regeneration. This project will examine the role of EphA4, an important guidance protein, in neural cell regeneration. The goal is to understand the signalling mechanisms that inhibit regeneration in the central nervous system and to develop novel biological agents to overcome these processes and promote functional recovery after nervous system injury or disease.
Click chemistry to reveal how neurons and glia shape perineuronal nets . The extracellular matrix (ECM) and its perineuronal nets (which are net-like structures with holes wrapped around neurons) are largely underexplored, despite representing a remarkable 20% of the brain’s total volume and having been suggested to be involved in many brain functions. Interestingly, digestion of the ECM improves learning and memory, but deficits return once the ECM has reformed. However, how this ECM remodellin ....Click chemistry to reveal how neurons and glia shape perineuronal nets . The extracellular matrix (ECM) and its perineuronal nets (which are net-like structures with holes wrapped around neurons) are largely underexplored, despite representing a remarkable 20% of the brain’s total volume and having been suggested to be involved in many brain functions. Interestingly, digestion of the ECM improves learning and memory, but deficits return once the ECM has reformed. However, how this ECM remodelling is organised at a cell-type level is not understood. Here we aim to close this knowledge gap, using cutting-edge technology including bioconjugation and ultrasound-mediated cargo delivery. Together, this project aims to contribute to a deeper understanding of this major brain compartment in neuronal function. Read moreRead less