Perturbation of the extracellular architecture to promote the absorption and lymphatic transport of biological macromolecules. Macromolecules therapeutics such as proteins, antibodies or polymer conjugates pose a number of pharmaceutical challenges. Where the dose is high, drainage of that dose from a subcutaneous injection site into the circulation, poses a particular problem. Here the project aims to explore how recombinant hyaluronidase, an enzyme that breaks down a structural component (hya ....Perturbation of the extracellular architecture to promote the absorption and lymphatic transport of biological macromolecules. Macromolecules therapeutics such as proteins, antibodies or polymer conjugates pose a number of pharmaceutical challenges. Where the dose is high, drainage of that dose from a subcutaneous injection site into the circulation, poses a particular problem. Here the project aims to explore how recombinant hyaluronidase, an enzyme that breaks down a structural component (hyaluronan) of the interstitum, can be used promote absorption into the draining blood and lymph capillaries. The project aims to also explore the downstream effects of hyaluronidase on lymph nodes and evaluate whether the enzyme is able to temporarily disrupt the lymph node structure and promote drug penetration into the lymph node mass. This has significant potential for improved drug targeting.Read moreRead less
Understanding the Cellular Pathways of Nuclear Receptor Activation. The success of drug treatment depends critically on specificity, i.e., stimulation of a therapeutic response at a target site, and avoidance of activity at other (potentially toxic) locations. This project aims to explore how drug interactions with binding proteins in the cytosol can induce nuclear transport and tissue specific activation of nuclear receptors - a major drug target. The project intends to employ molecular, struct ....Understanding the Cellular Pathways of Nuclear Receptor Activation. The success of drug treatment depends critically on specificity, i.e., stimulation of a therapeutic response at a target site, and avoidance of activity at other (potentially toxic) locations. This project aims to explore how drug interactions with binding proteins in the cytosol can induce nuclear transport and tissue specific activation of nuclear receptors - a major drug target. The project intends to employ molecular, structural and cell biology approaches to map drug-binding protein-receptor interactions and to determine how the structure of these complexes dictates receptor activation. The data could provide a roadmap to design drugs that interact with the right protein in the right tissue and in doing so dramatically enhance drug specificity.Read moreRead less
Synergising nanoemulsion and lipid biomimetic design for advanced delivery. This project aims to identify the critical design characteristics of lipid formulations of lipid-modified probes or drugs (lipid biomimetics) that together promote integration into lipid absorption pathways and target the lymphatic system that drains the small intestine. This has significant potential since the intestinal lymphatic system is a key immune tissue, the site of immune response to autoantigens and antigens de ....Synergising nanoemulsion and lipid biomimetic design for advanced delivery. This project aims to identify the critical design characteristics of lipid formulations of lipid-modified probes or drugs (lipid biomimetics) that together promote integration into lipid absorption pathways and target the lymphatic system that drains the small intestine. This has significant potential since the intestinal lymphatic system is a key immune tissue, the site of immune response to autoantigens and antigens derived from food and the microbiome. The project will deliver a design roadmap of the required characteristics for lymphatic targeting, and in particular, will identify novel lipid nanoemulsions that work synergistically with lipid biomimetics to enhance lymphatic imaging and delivery applications.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120103084
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Targeting bacterial superbugs: novel approaches for optimisation of antibiotic combinations and resistance prevention. This project will elucidate the mechanistic basis to optimally combine available beta-lactam antibiotics to prevent resistance of gram-negative 'superbugs'. The interdisciplinary project will substantially contribute to solving the global crisis due to multidrug-resistant bacteria and inform the design of effective new antibiotics.
Targeting an impending global disaster: the mismatch between increasingly drug-resistant superbugs and development of new antibiotics. This project will develop much-needed novel antibiotics for treating infections caused by bacteria that are resistant to all current antibiotics. It will make a significant contribution to the global medical challenge of a shortage of new antibiotics.
Light-responsive nanomaterials as nanomedicines: new approaches to treating macular degeneration, cancer and other critical unmet therapeutic needs. Nanotechnology is enabling new medicines for the treatment of important diseases such as cancer and macular degeneration. This project will investigate novel nanomaterials for the development of new highly effective medicines that can be controlled after administration, leading to reduced side effects and increased convenience for patients.
Controlling the spatial distribution of targeting ligands on dendrimer surfaces as a means of dictating cellular recognition and fate. This project seeks to develop next generation targeted drug delivery systems that 'home' to specific target cells, including cancers. Targeted delivery systems have the potential to revolutionise therapy by providing bespoke drug distribution patterns that are tailored to specific diseases and result in enhanced activity and reduced toxicity.
Industrial Transformation Training Centres - Grant ID: IC180100021
Funder
Australian Research Council
Funding Amount
$4,163,359.00
Summary
ARC Training Centre for the Development of Tools for Fragment Based Design. The ARC Training Centre for the Development of Tools for Fragment Based Design aims to inspire the next generation of drug discovery research leaders. It plans to provide direct experience with industry partners, training and master classes in early stage drug-discovery from industry experts. The Centre is expected to accelerate research translation and industry engagement by providing an efficient strategy for the scree ....ARC Training Centre for the Development of Tools for Fragment Based Design. The ARC Training Centre for the Development of Tools for Fragment Based Design aims to inspire the next generation of drug discovery research leaders. It plans to provide direct experience with industry partners, training and master classes in early stage drug-discovery from industry experts. The Centre is expected to accelerate research translation and industry engagement by providing an efficient strategy for the screening of a biological target and early medicinal chemistry for optimisation. The expected outcome of the Centre is to equip the trainees with the skills to make key contributions to the sustainability and growth of the sector and to provide significant capacity to address global challenges for 21st century pharmaceutical innovation.Read moreRead less
Functional Materials to Hijack on Lipid Transport Pathways. This Project aims to provide new design rules for novel polymers with lipid elements that would allow them to interact with natural lipid trafficking pathways in precise ways.
The anticipated goal is to generate a greater understanding on how these materials co-opt lipid transport pathways, serum albumins and lipoprotein nanoparticle assemblies, as a function of lipid component, molecular weight and macromolecular structure.
Expected ....Functional Materials to Hijack on Lipid Transport Pathways. This Project aims to provide new design rules for novel polymers with lipid elements that would allow them to interact with natural lipid trafficking pathways in precise ways.
The anticipated goal is to generate a greater understanding on how these materials co-opt lipid transport pathways, serum albumins and lipoprotein nanoparticle assemblies, as a function of lipid component, molecular weight and macromolecular structure.
Expected outcomes of this project may be novel lipid functional materials with tuneable pharmokinetics, plasma exposure, lymph exposure and biodistribution. These materials would have wide application in the pharmaceutical and veterinary industries.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668493
Funder
Australian Research Council
Funding Amount
$230,000.00
Summary
Characterising particulate laden flow in the lung airways: from drug delivery to primary anthropogenic sources. Facilities will provide infrastructure at Monash University and University of Sydney to continue the collaboration enhancing excellence in an exciting application of fluidics research, supporting the highest level of graduate training, providing innovative tools for industry and promoting industrial collaborations. The infrastructure is unique and will create international funding and ....Characterising particulate laden flow in the lung airways: from drug delivery to primary anthropogenic sources. Facilities will provide infrastructure at Monash University and University of Sydney to continue the collaboration enhancing excellence in an exciting application of fluidics research, supporting the highest level of graduate training, providing innovative tools for industry and promoting industrial collaborations. The infrastructure is unique and will create international funding and collaborative opportunities to support research and postgraduate training. The equipment will add value to existing infrastructure to enhance understanding of particulate flow with the paradoxical outcomes of improving drug deposition in respiratory delivery and of minimising anthropogenic particular deposition for better therapeutic and health outcomes.Read moreRead less