Development of novel therapies for the treatment of cancer. Both aging and obesity are significant risk factors for cancer and are becoming a burden on the health care budget. The proposed novel cancer therapy will improve current cancer treatments by enhancing their efficacy, thereby reducing the required dose and minimizing side effects. Such an outcome would not only benefit the well being of the individual but would achieve significant health care cost savings.
Novel antimicrobial target discovery by an integrated approach. The project aims to uncover the molecular targets of BDM-I, a novel antimicrobial candidate discovered by the start-up Australian company BioDiem Ltd. BDM-I is active against many drug resistant bacterial and fungal microorganisms and it is currently in pre-clinical development. However, the lack of resistant phenotypes makes it difficult to identify BDM-I’s mechanism of action. The project plans to use an integrated approach that c ....Novel antimicrobial target discovery by an integrated approach. The project aims to uncover the molecular targets of BDM-I, a novel antimicrobial candidate discovered by the start-up Australian company BioDiem Ltd. BDM-I is active against many drug resistant bacterial and fungal microorganisms and it is currently in pre-clinical development. However, the lack of resistant phenotypes makes it difficult to identify BDM-I’s mechanism of action. The project plans to use an integrated approach that combines a novel technique of in silico screening with experimental validation. Project outcomes are anticipated to include the first computational method to integrate target and ligand similarity for proteome-scale target and off-target discovery, which will advance the global fight against drug-resistant microorganisms.Read moreRead less
Application of direct protein transduction of Stem Cell Factors to reprogram mouse and human somatic cells into pluripotent stem cells. This project aims to generate embryonic stem cell-like cells from human somatic cells, using direct protein transduction of defined factors, rather than through retroviral delivery. This will bring stem cell application closer to a therapeutic setting. The cells produced will be free from genetic modification and will yield products for patient-specific cell-ba ....Application of direct protein transduction of Stem Cell Factors to reprogram mouse and human somatic cells into pluripotent stem cells. This project aims to generate embryonic stem cell-like cells from human somatic cells, using direct protein transduction of defined factors, rather than through retroviral delivery. This will bring stem cell application closer to a therapeutic setting. The cells produced will be free from genetic modification and will yield products for patient-specific cell-based therapies that will be accepted by recipients without the need for immunosuppressant therapy. This development is expected to revolutionize the current approach to treating disease and injury, and is likely to result in the generation of highly marketable potent cell reprogramming therapeutics.Read moreRead less
Metalloproteomics: A new piece of the systems biology puzzle. Systems biology uses advanced analytical technology to study the complex chemistry of the living cell. Many cellular functions are the result of chemical reactions involving metalloproteins, which are notoriously difficult to study due to the weak bonds between metal and protein that is not normally amenable to traditional proteomic approaches. In partnership with the leading analytical manufacturer Agilent Technologies, this project ....Metalloproteomics: A new piece of the systems biology puzzle. Systems biology uses advanced analytical technology to study the complex chemistry of the living cell. Many cellular functions are the result of chemical reactions involving metalloproteins, which are notoriously difficult to study due to the weak bonds between metal and protein that is not normally amenable to traditional proteomic approaches. In partnership with the leading analytical manufacturer Agilent Technologies, this project aims to adapt and apply advanced mass spectrometry to the study of metalloproteins, developing new methods for studying hundreds of molecules in single experiments. Using the C. elegans model organism the project aims to showcase the importance of metals in biology and develop new solutions for the $2.9 billion proteomics industry.Read moreRead less
Neurons isolated from embryonic stem cells as functional models for drug discovery. By using gene expression-based selection criteria embryonic stem cells can be driven to differentiate into specific neuronal lineages which show many of the morphological characteristics and immunocytochemical features of neurons in culture. There is, however, comparatively little evidence indicating that these stem cell-derived neurons actually behave as neurons. Our aim is to characterise and contrast four ne ....Neurons isolated from embryonic stem cells as functional models for drug discovery. By using gene expression-based selection criteria embryonic stem cells can be driven to differentiate into specific neuronal lineages which show many of the morphological characteristics and immunocytochemical features of neurons in culture. There is, however, comparatively little evidence indicating that these stem cell-derived neurons actually behave as neurons. Our aim is to characterise and contrast four neuronal cell cultures established with gene-based selection criteria. These cultures will be characterised by gene expression, immunocytochemistry, radiolabelled neurotransmitter release, electrophysiology and Ca2+ imaging studies. This study will highlight the functional effects of gene selection procedures upon stem cell-derived neurons.Read moreRead less
The atlas of trace metals in the mouse brain: a new tool for neuroscientists. This project will produce the first atlas of trace metals in the mouse brain: a set of 'maps' of a type of brain often used to study diseases affecting the human brain. This online resource will show neuroscientists unprecedented 3D detail of the distribution in the brain of trace metals, which are implicated in such diseases as Parkinson's and Alzheimer's.
Feeding and digestion in tropical rock lobster phyllosoma larvae and its applications for culture. Provision of larval culture diets that provide optimal nutrition in a suitable presentation format is the major challenge for developing a rock lobster aquaculture industry. Tropical rock lobsters are likely contenders due to their faster growth rates and shorter larval phase than temperate species. This project will assess the ingestive and digestive capabilities of larvae during development, thro ....Feeding and digestion in tropical rock lobster phyllosoma larvae and its applications for culture. Provision of larval culture diets that provide optimal nutrition in a suitable presentation format is the major challenge for developing a rock lobster aquaculture industry. Tropical rock lobsters are likely contenders due to their faster growth rates and shorter larval phase than temperate species. This project will assess the ingestive and digestive capabilities of larvae during development, through an examination of mouthpart and gut structure and their types and concentration of digestive enzymes. Information will be used to formulate and test improved diets of appropriate size, texture and nutritional composition and will be the first comprehensive analysis of preferred larval diets on the basis of their biological and physiological characteristics.Read moreRead less
Developing macrophage-based technologies for tissue regeneration. Different tissues show distinct regenerative capacities with an organism and across the phylogeny. What underlies this diversity in regenerative ability at cellular and molecular level is far from clear. Building on foundational discoveries in zebrafish, this study seeks to determine if this capacity could, in part, be explained through the properties of a component of the innate immune system, the macrophage, which preliminary da ....Developing macrophage-based technologies for tissue regeneration. Different tissues show distinct regenerative capacities with an organism and across the phylogeny. What underlies this diversity in regenerative ability at cellular and molecular level is far from clear. Building on foundational discoveries in zebrafish, this study seeks to determine if this capacity could, in part, be explained through the properties of a component of the innate immune system, the macrophage, which preliminary data shows generates a transient pro-regenerative muscle stem cell niche in zebrafish. This study will determine if macrophage subtypes acts to coordinate regeneration in other tissues and systems and if a programable pro-regenerative cell can be made in vitro that stimulate regeneration in different settings.Read moreRead less
Why is the photosynthetic CO2-fixing enzyme, Rubisco, so inefficient? Dissection of the catalytic chemistry by computational simulation and experimental testing. Fixation of CO2 by the enzyme Rubisco during photosynthesis produces organic compounds which feed all life. Despite this critical role, Rubisco catalyses its reaction sluggishly and, worse, discriminates poorly between CO2 and O2, leading to useless products. Our combined expertise equips us to analyse Rubisco's mechanism using quantum- ....Why is the photosynthetic CO2-fixing enzyme, Rubisco, so inefficient? Dissection of the catalytic chemistry by computational simulation and experimental testing. Fixation of CO2 by the enzyme Rubisco during photosynthesis produces organic compounds which feed all life. Despite this critical role, Rubisco catalyses its reaction sluggishly and, worse, discriminates poorly between CO2 and O2, leading to useless products. Our combined expertise equips us to analyse Rubisco's mechanism using quantum-chemical methods and then test predictions experimentally. We will capitalise on our previous successful studies of Rubisco by addressing emergent issues which are the keys to understanding catalytic efficiency and CO2/O2 selectivity: the roles of a carbamylated lysine; the way CO2 addition is rendered irreversible; and the spin inversion inherent in O2 addition.Read moreRead less
Studies of the pi3-kinase enzyme family using selective inhibitors. The objective of this project is to study the function of the PI3-kinase enzyme family in blood platelets. To do this, inhibitors which block the action of specific family members, will be evaluated for their effects in assays of platelet function. The results will enhance our understanding of the way in which platelets and other cells respond to stimuli, and lead new approaches to designing novel drugs that block these response ....Studies of the pi3-kinase enzyme family using selective inhibitors. The objective of this project is to study the function of the PI3-kinase enzyme family in blood platelets. To do this, inhibitors which block the action of specific family members, will be evaluated for their effects in assays of platelet function. The results will enhance our understanding of the way in which platelets and other cells respond to stimuli, and lead new approaches to designing novel drugs that block these responses.Read moreRead less