We have discovered a single tumour factor which causes cancer cachexia, a wasting condition that is one of the worst complications of malignancy, for which there is no current effective treatment. We have developed antibodies which effectively block this condition in preclinical models and have produced human/humanised version of this. This application is to characterise these human antibodies to allow us proceed to clinical trials.
Mechanisms And Therapies In Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$8,360,700.00
Summary
Cardiovascular disease (CVD) claims 1 person every 10 min in Australia and causes 1 in 3 deaths worldwide. The molecular and cellular processes underlying atherosclerosis, vascular injury and thrombosis are highly complex and not well understood. A multifaceted approach is needed to effectively address these key challenges. This Program brings together world experts in these areas to interrogate gaps in our basic understanding of CVD, and to develop novel therapies for CVD patients by exploiting ....Cardiovascular disease (CVD) claims 1 person every 10 min in Australia and causes 1 in 3 deaths worldwide. The molecular and cellular processes underlying atherosclerosis, vascular injury and thrombosis are highly complex and not well understood. A multifaceted approach is needed to effectively address these key challenges. This Program brings together world experts in these areas to interrogate gaps in our basic understanding of CVD, and to develop novel therapies for CVD patients by exploiting new knowledge through integrated research.Read moreRead less
Topological stability from spectral analysis. The aim is to use mathematical scattering theory to find and study new topological features of the spectra of linear transformations on Hilbert space. The significance derives from mathematical models of low temperature conducting quantum materials. These have revealed `topological phases of matter' that are stable with respect to a range of variations in the parameters that determine the system. The stability is desired for applications to quantum ....Topological stability from spectral analysis. The aim is to use mathematical scattering theory to find and study new topological features of the spectra of linear transformations on Hilbert space. The significance derives from mathematical models of low temperature conducting quantum materials. These have revealed `topological phases of matter' that are stable with respect to a range of variations in the parameters that determine the system. The stability is desired for applications to quantum devices. Our results will give topological stability from the scattering spectrum, a feature not previously seen. The benefits stem from new results in mathematical scattering theory with a primary novelty being the analysis of ``zero energy resonances'' in mathematical models of graphene.Read moreRead less
A multiplex microscope platform to define molecular events in fluid systems. This project aims to develop a novel microscopy platform that will enable the visualisation and quantification of molecular events occurring under fluid shear stress. The project will generate new knowledge in platelet biology that will allow characterisation and prediction of key molecular and morphological changes occurring across a blood thrombus under flowing conditions as found in the blood vessels. These new tools ....A multiplex microscope platform to define molecular events in fluid systems. This project aims to develop a novel microscopy platform that will enable the visualisation and quantification of molecular events occurring under fluid shear stress. The project will generate new knowledge in platelet biology that will allow characterisation and prediction of key molecular and morphological changes occurring across a blood thrombus under flowing conditions as found in the blood vessels. These new tools and the imaging platform will have applications for researchers wishing to visualise small and rapid molecular events in four dimensions (length, width, height and across time) under fluid shear stress, which is applicable across a range of industries. The project expects to deliver the next generation of intravital microscopes that can visualise and quantify events in a challenging flow environment.Read moreRead less
Integrin Activation by Fluid Flow Disturbance: Mechanobiology Approaches. Understanding how cells can sense and respond to mechanical environment such as dynamic blood flow represents a fundamental question in the emerging field of mechanobiology. This project develops new biomechanical engineering approaches to determine the critical interrelationships among fluid flow disturbance, platelet clotting and the mechano-sensitive signal transduction mechanisms of integrin receptor – the most importa ....Integrin Activation by Fluid Flow Disturbance: Mechanobiology Approaches. Understanding how cells can sense and respond to mechanical environment such as dynamic blood flow represents a fundamental question in the emerging field of mechanobiology. This project develops new biomechanical engineering approaches to determine the critical interrelationships among fluid flow disturbance, platelet clotting and the mechano-sensitive signal transduction mechanisms of integrin receptor – the most important mechano-sensor implicated in cell adhesion, migration, growth and survival. Specifically, it integrates nationally unique cutting-edge techniques including single-molecule force probe, microparticle image velocimetry, microfluidics and molecular dynamics simulation, super resolution and 3D volumetric imaging modalities.Read moreRead less
5D Imaging Flow Cytometry for in vivo Quantification of Biological Fluids. Rapid and accurate quantification of live biological fluid properties at sub-cellular and molecular levels forms the bedrock of biofluidic sciences. Majority of the biofluidic devices rely on quantifying biological fluids after its removal from the body in an in vitro Flow Cytometer (FC). FC faces many caveats i.e. biological degradation and small volume etc. In this project, we shall engineer the first in vivo 5D imaging ....5D Imaging Flow Cytometry for in vivo Quantification of Biological Fluids. Rapid and accurate quantification of live biological fluid properties at sub-cellular and molecular levels forms the bedrock of biofluidic sciences. Majority of the biofluidic devices rely on quantifying biological fluids after its removal from the body in an in vitro Flow Cytometer (FC). FC faces many caveats i.e. biological degradation and small volume etc. In this project, we shall engineer the first in vivo 5D imaging flow cytometer (5D IFC) capable of continuous assessment of potentially entire blood volume in a living mice without removing fluid out of the body. The project represents a major advancement beyond any existing flow cytometer and overcome the engineering limits of state-of-art laser scanning imaging devices.Read moreRead less
Topology optimisation of mechanical metamaterials with additive manufacture. Metamaterials have sparked a surge of interest with potential applications as diverse as biomedical implants, ballistic barriers, and acoustic cloaks. This project aims to develop topology optimisation technology, with the marriage of additive manufacturing for computational design of mechanical metamaterials of pentamode, which are a new class of artificial composites engineered to have elastic properties not easily fo ....Topology optimisation of mechanical metamaterials with additive manufacture. Metamaterials have sparked a surge of interest with potential applications as diverse as biomedical implants, ballistic barriers, and acoustic cloaks. This project aims to develop topology optimisation technology, with the marriage of additive manufacturing for computational design of mechanical metamaterials of pentamode, which are a new class of artificial composites engineered to have elastic properties not easily found in nature. This approach aims to create novel metamaterials to have extraordinary properties and complex geometries that can be easily fabricated. Potential applications may include defense, vehicles, biomedicine, marine uses, energy and cloaks.Read moreRead less
Thermal transport in multi-phase flows for concentrating solar applications. This project seeks to advance the field of heat transfer in high-temperature systems involving liquid metals, with emphasis on energy storage and solar power technologies. The concept couples a tubular sodium boiler with a sodium chloride phase-change storage system for continuous energy supply. Sodium chloride is low cost and has a melting temperature suitable for a wide range of industrial processes. The project plans ....Thermal transport in multi-phase flows for concentrating solar applications. This project seeks to advance the field of heat transfer in high-temperature systems involving liquid metals, with emphasis on energy storage and solar power technologies. The concept couples a tubular sodium boiler with a sodium chloride phase-change storage system for continuous energy supply. Sodium chloride is low cost and has a melting temperature suitable for a wide range of industrial processes. The project plans to address the challenge of sodium stability in highly irradiated tubes by investigating mass, momentum, energy and radiative transport in liquid metals. It is intended that this will inform the design and testing of novel sodium boilers to provide stable and isothermal process heat for continuous or on-demand production of power, chemical fuels and commodities.Read moreRead less
Entrainment and Mixing in Turbulent Negatively Buoyant Jets and Fountains. The project intends to develop tools to accurate predict fountain flows. Volcanic eruptions, building ventilation and brine discharge from desalination plants are all examples of turbulent fountains and negatively buoyant jets. The project aims to conduct an investigation into the turbulent structure of fountains and negatively buoyant jets using numerical simulation and laboratory experiments, and to assess the accuracy ....Entrainment and Mixing in Turbulent Negatively Buoyant Jets and Fountains. The project intends to develop tools to accurate predict fountain flows. Volcanic eruptions, building ventilation and brine discharge from desalination plants are all examples of turbulent fountains and negatively buoyant jets. The project aims to conduct an investigation into the turbulent structure of fountains and negatively buoyant jets using numerical simulation and laboratory experiments, and to assess the accuracy of the commonly used integral models and test the effect of the use of more accurate entrainment relations. This may have a range of applications – enabling better prediction of environmental impacts, reduction of the adverse effects of the discharge of pollutants, and reduction in energy consumption in building ventilation and other industrial applications.Read moreRead less
Baseline-free Methods for Early Damage Diagnosis using Nonlinear Ultrasound. To address the significant limitation of existing non-destructive evaluation techniques in detecting and characterising early damage, this project aims to discover the physical nature of self-generated nonlinear waves by structural damage and to explore its potential for an entirely new class of non-destructive evaluation and structural health monitoring techniques. Major applications are expected to include a baseline- ....Baseline-free Methods for Early Damage Diagnosis using Nonlinear Ultrasound. To address the significant limitation of existing non-destructive evaluation techniques in detecting and characterising early damage, this project aims to discover the physical nature of self-generated nonlinear waves by structural damage and to explore its potential for an entirely new class of non-destructive evaluation and structural health monitoring techniques. Major applications are expected to include a baseline-free structural health monitoring technique capable of detecting and quantifying barely-visible impact damage in advanced composite materials, non-destructive evaluation of structures made by additive manufacturing, and detection of hard-to-inspect locations in unitised structures.Read moreRead less