IMMUNOTARGETED NANOPARTICLES TO IMPROVE TUMOUR DELIVERY OF CHEMOSENSITISING CYTOTOXIC DRUGS AND B-RADIATION
Funder
National Health and Medical Research Council
Funding Amount
$548,985.00
Summary
This project aims to develop nano-bullets for advanced cancer therapy and nano-probes for the early assessment of cancer treatment responses, improved patient outcomes and reducing drug development time. Specially engineered, antibody-coated nanoparticles are targeted to dead cancer cells, present in untreated cancer but increased after therapy, for (1) tumour site specific delivery of increased drug or radiation dose than currently achieved and (2) monitoring the tumour response to therapy.
Inhibitors Of Bacterial Protein Synthesis - A New Class Of Antibiotics
Funder
National Health and Medical Research Council
Funding Amount
$120,000.00
Summary
Pioneering work by CSIRO scientists has identified specific peptide motifs in the DNA replication machinery of bacteria that are critical for the correct functioning of the organism. In collaboration with CI Alewood potent (Kd ~ nM) lead compounds that inhibit bacterial DNA replication have been designed and synthesised. Through the application of a number of novel bioinformatics approaches to the analysis of the complete genome sequences of bacteria, the key sites of interaction of a number of ....Pioneering work by CSIRO scientists has identified specific peptide motifs in the DNA replication machinery of bacteria that are critical for the correct functioning of the organism. In collaboration with CI Alewood potent (Kd ~ nM) lead compounds that inhibit bacterial DNA replication have been designed and synthesised. Through the application of a number of novel bioinformatics approaches to the analysis of the complete genome sequences of bacteria, the key sites of interaction of a number of protein families (DNA synthesis and repair enzymes) with the beta subunit of bacterial DNA Polymerase III have been identified. The nature of the sites, and preliminary experimental data, suggests that the approach will be generally applicable to all species of bacteria. In addition a wide range of novel assays for the identification of inhibitors of the interaction of proteins with the beta subunit have been developed. In this proposal we wish to demonstrate that our in vitro nanomolar inhibitors of the beta subunit can inhibit bacterial cell growth. The development program proposes to develop methods and strategies to gain bacterial cell entry of inhibitors of the interaction of proteins with the beta subunit of bacterial DNA Polymerase III. Proof of concept will be demonstrated by inhibition of bacterial cell growth. Stable compounds with good binding characteristics and able to be taken up by cells will be developed based on structure-function assay results, structural studies and modelling of inhibitors bound to the target. Antimicrobial activity of compounds will be demonstrated in standard FDA approved NCLLS (National Centre of Clinical Laboratory Standards USA) tests. Spectrum of activity will be demonstrated by testing compounds against bacterial species representative of the range of pathogenic organisms in standard FDA assays.Read moreRead less
New peptides to probe protein kinase functions. We are building on our expertise in biochemistry, molecular biology and biotechnology, to develop and exploit new technologies that enable the discovery and characterisation of new peptides that probe protein kinase functions. An important application of work will be in the development of new leads for drug design, as highlighted by the success of some protein kinase inhibitors as drugs. The immediate benefits of our research will come with enhance ....New peptides to probe protein kinase functions. We are building on our expertise in biochemistry, molecular biology and biotechnology, to develop and exploit new technologies that enable the discovery and characterisation of new peptides that probe protein kinase functions. An important application of work will be in the development of new leads for drug design, as highlighted by the success of some protein kinase inhibitors as drugs. The immediate benefits of our research will come with enhanced interactions in the international academic and biotechnology arenas and with the training of post-graduate and post-doctoral staff. This research training will greatly enrich Australian biotechnology expertise.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882855
Funder
Australian Research Council
Funding Amount
$900,000.00
Summary
High-resolution imaging of live cells and tissue. Understanding the machinery of life and developing technologies that support life's processes requires biological and physical scientists and engineers to monitor molecular events in living systems. The aim is to take advantage of very recent developments in light microscopy to enable the non-invasive imaging of live cells and tissue at a previously unreachable level of detail. The instruments will form the nucleus of a new imaging facility. Sign ....High-resolution imaging of live cells and tissue. Understanding the machinery of life and developing technologies that support life's processes requires biological and physical scientists and engineers to monitor molecular events in living systems. The aim is to take advantage of very recent developments in light microscopy to enable the non-invasive imaging of live cells and tissue at a previously unreachable level of detail. The instruments will form the nucleus of a new imaging facility. Significant advances in research areas including vascular research, cancer, immunology, cell and molecular biology, functional genomics, biotechnology, nanotechnology and material engineering will be of major benefit both nationally and globally.Read moreRead less
Rational structure-based drug design of protein tyrosine kinase inhibitors. Protein tyrosine kinases (PTK) are a large, pivotal family of signalling molecules implicated in diseases such as cancer and immune-related disorders, that cause significant morbidity and mortality within the population. This research proposal aims to develop PTK-specific small molecule inhibitors to combat such diseases. Cytopia's drug discovery capability, coupled with the X-ray crystallographic expertise within Monas ....Rational structure-based drug design of protein tyrosine kinase inhibitors. Protein tyrosine kinases (PTK) are a large, pivotal family of signalling molecules implicated in diseases such as cancer and immune-related disorders, that cause significant morbidity and mortality within the population. This research proposal aims to develop PTK-specific small molecule inhibitors to combat such diseases. Cytopia's drug discovery capability, coupled with the X-ray crystallographic expertise within Monash University, will permit a rational, structure-based drug discovery platform to be established. The ultimate goal of this innovative and mutlidisciplinary approach, namely a portfolio of phase I therapeutics, will be of substantial benefit in the medical health area.Read moreRead less
Rational structure-based drug design of protein tyrosine kinase inhibitors. This research project is focussed on understanding the physiological roles of a group of enzymes within the cell, as well as developing therapeutics to combat significant diseases. It will achieve this by developing compounds to enzymes that are implicated in the disease process. The research project represents a continuation of a collaboration between academic researchers at Monash University, and an Australian biotec ....Rational structure-based drug design of protein tyrosine kinase inhibitors. This research project is focussed on understanding the physiological roles of a group of enzymes within the cell, as well as developing therapeutics to combat significant diseases. It will achieve this by developing compounds to enzymes that are implicated in the disease process. The research project represents a continuation of a collaboration between academic researchers at Monash University, and an Australian biotechnology company, Cytopia Ltd.Read moreRead less
Enhancement of monopartite geminivirus pathogenicity by satellite DNA beta encoded betaC1 protein: the role of host factors. Australian incursions of geminiviruses are uncontrollable due to their unique mode of spread by whiteflies. The first incursion in Darwin in 1970 has spread to Far Northern Queensland. The second in SE Queensland in 2006 is estimated to cause $500 million loss to horticulture. Our $2 billion cotton industry is threatened by cotton leaf curl diseases from South Asia, where ....Enhancement of monopartite geminivirus pathogenicity by satellite DNA beta encoded betaC1 protein: the role of host factors. Australian incursions of geminiviruses are uncontrollable due to their unique mode of spread by whiteflies. The first incursion in Darwin in 1970 has spread to Far Northern Queensland. The second in SE Queensland in 2006 is estimated to cause $500 million loss to horticulture. Our $2 billion cotton industry is threatened by cotton leaf curl diseases from South Asia, where DNA beta enhances virus replication and disease severity. DNA beta has the potential to enter Australia with several different geminiviruses and to spread into others by co-infection, which requires research on detection and pathogenesis of DNA beta.Read moreRead less
Investigation of Macrophage Function in an Immunologically Privileged Site. The unique phenotype of the testicular macrophage demands understanding, and this project has the potential to open up an entirely new direction of research. The basic information so generated could facilitate development of strategies to alter either host or donor tissue macrophage functions in order to prevent rejection responses in humans, and be used in the development of new anti-inflammatory drugs. Such technologie ....Investigation of Macrophage Function in an Immunologically Privileged Site. The unique phenotype of the testicular macrophage demands understanding, and this project has the potential to open up an entirely new direction of research. The basic information so generated could facilitate development of strategies to alter either host or donor tissue macrophage functions in order to prevent rejection responses in humans, and be used in the development of new anti-inflammatory drugs. Such technologies will have application in development of novel therapeutics for transplantation and the treatment of chronic inflammatory diseases. Read moreRead less
Multiplexed Molecular Reading of Protein Associations via Nanoscaled Devices. Current developments in Nanoscience and Nanotechnology hold many promises in terms of revolutionising our industrial base, transforming biology, medical science and practice. This project strives to achieve some of these goals by, for the first time, building and testing nano-scaled devices with the capability to rapidly ?read? information about complex protein associations. With the recent completion of the Human Ge ....Multiplexed Molecular Reading of Protein Associations via Nanoscaled Devices. Current developments in Nanoscience and Nanotechnology hold many promises in terms of revolutionising our industrial base, transforming biology, medical science and practice. This project strives to achieve some of these goals by, for the first time, building and testing nano-scaled devices with the capability to rapidly ?read? information about complex protein associations. With the recent completion of the Human Genome project, major opportunities exist to provide spectacular advances in human health care (eg, via novel diagnostics) provided that appropriate high-throughput biological reading devices can be developed. In developing such devices, this project also aims to catalyse the Australian Nanotechnology/Biotechnology industry.Read moreRead less