Characterisation and Development of Dynamic Supramolecular Combinatorial Libraries. The discovery of biologically active molecules, in particular drug discovery, requires the design and synthesis of host molecules that bind selectively to the biological target. Combinatorial chemistry has greatly assisted this discovery process as it allows the rapid screening of large collections of molecules. In this proposal, metal ion interactions will be used in the combinatorial library as this will grea ....Characterisation and Development of Dynamic Supramolecular Combinatorial Libraries. The discovery of biologically active molecules, in particular drug discovery, requires the design and synthesis of host molecules that bind selectively to the biological target. Combinatorial chemistry has greatly assisted this discovery process as it allows the rapid screening of large collections of molecules. In this proposal, metal ion interactions will be used in the combinatorial library as this will greatly increases the diversity of the pool of compounds to be screened for activity. Understanding how to generate and analyze these libraries has potential applications in drug screening, the discovery of new substrates, enzymes and inhibitors. Read moreRead less
Synthesis of Bioactive Metabolites from Myxobacteria. The crocacins and apicularens are two diverse groups of biologically active molecules isolated from myxobacteria. Crocacins A-D are dipeptides which show antifungal activity and are highly cytostatic in mammalian cell cultures. The novel macrolide apicularen A is highly active against a number of human tumour cell lines and shows promise as a new type of anticancer compound. The aim of this project is develop a methodology to synthesise these ....Synthesis of Bioactive Metabolites from Myxobacteria. The crocacins and apicularens are two diverse groups of biologically active molecules isolated from myxobacteria. Crocacins A-D are dipeptides which show antifungal activity and are highly cytostatic in mammalian cell cultures. The novel macrolide apicularen A is highly active against a number of human tumour cell lines and shows promise as a new type of anticancer compound. The aim of this project is develop a methodology to synthesise these novel compounds.Read moreRead less
Enabling Methodologies for the Synthesis of Biologically Active Compounds. This project seeks to establish flexible methods of chemical synthesis for creating new molecular scaffolds capable of achieving selective enzyme inhibition. The approach aims to exploit the vast and biologically-programmed structural diversity associated with natural products. Unique, small molecule organic compounds will be obtained that reveal details of the operation of key enzymes in bacterial and mammalian systems. ....Enabling Methodologies for the Synthesis of Biologically Active Compounds. This project seeks to establish flexible methods of chemical synthesis for creating new molecular scaffolds capable of achieving selective enzyme inhibition. The approach aims to exploit the vast and biologically-programmed structural diversity associated with natural products. Unique, small molecule organic compounds will be obtained that reveal details of the operation of key enzymes in bacterial and mammalian systems. Such new knowledge would allow for the design of highly selective therapeutic agents relevant to the treatment of a range of diseases including bacterial infections, diabetes and cancer. The high-end scientific training and privileged forms of matter arising from this work would provide major benefit to the biotech sector.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240100793
Funder
Australian Research Council
Funding Amount
$463,180.00
Summary
Unraveling a new cytokine working model in immune cell exhaustion. This project will investigate a novel paradigm of how a key messenger protein can be sensed by fundamental immune cells, preventing their ‘exhaustion’. Immune cell exhaustion is a fundamental mechanism to maintain the internal homeostasis of vertebrates. However, it is often hijacked by pathogens to dampen the defensive capacity of the immune system. And this specific messenger protein is the only known soluble factor that can d ....Unraveling a new cytokine working model in immune cell exhaustion. This project will investigate a novel paradigm of how a key messenger protein can be sensed by fundamental immune cells, preventing their ‘exhaustion’. Immune cell exhaustion is a fundamental mechanism to maintain the internal homeostasis of vertebrates. However, it is often hijacked by pathogens to dampen the defensive capacity of the immune system. And this specific messenger protein is the only known soluble factor that can deliver ‘anti-exhaustion’ signals to immune cells. This study will advance basic knowledge in biochemistry and immunology by combining interdisciplinary and cutting-edge approaches. The expected outcomes include the developing new scientific theories and identifying novel molecular basis of biological processes. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160100293
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Cracking the phosphoinositide code. This project seeks to determine how protein interactions with membrane lipids regulate recruitment to cellular organelles, providing new insight into the complex pathways of cellular homeostasis. Controlling the distribution of proteins within cells is critical for cell signalling and membrane trafficking. This is orchestrated by the interaction of specific protein modules with lipids on the surface of different organelles. The phox homology (PX) domain is a l ....Cracking the phosphoinositide code. This project seeks to determine how protein interactions with membrane lipids regulate recruitment to cellular organelles, providing new insight into the complex pathways of cellular homeostasis. Controlling the distribution of proteins within cells is critical for cell signalling and membrane trafficking. This is orchestrated by the interaction of specific protein modules with lipids on the surface of different organelles. The phox homology (PX) domain is a lipid-binding module found in numerous proteins essential for normal cell trafficking and homeostasis, and perturbed in many conditions including immune dysfunction and cancer. This project plans to investigate molecular determinants of PX-lipid association, generating knowledge about protein-membrane interactions required for cellular function. These insights may underpin future drug design.Read moreRead less