Development of Insulin-like peptide 5 (INSL5) peptide analogues as novel therapeutics. Insulin-like peptide 5 (INSL5) is a naturally-occurring hormone in the body that likely plays a role in the control of appetite. This project aims to develop new molecules based on INSL5 that could be suitable for use as drugs to treat various appetite-related disorders, such as obesity (where patients eat too much) or anorexia (where patients eat too little).
Intracellular trafficking and function of a recycling receptor which prolongs the serum half-life of novel therapeutic proteins. The life span of recombinant engineered proteins for therapeutic use is a critical factor in their effectiveness, ease of clinical application and cost. This project will exploit interactions with a natural receptor, which prolongs the lifespan of serum proteins, to enhance survival of therapeutic engineered proteins.
Solid phase synthesis of side-chain cross-linked peptide oligomers. This research will provide a unique opportunity to investigate the biological pathways and causative factors leading to diseases such as Alzheimer’s disease. Such information will guide the design and development of therapeutic strategies and diagnostic reagents.
Thioamide ligations: new technologies for peptide and protein synthesis. This project aims to develop novel amide-bond forming reactions for the chemical synthesis of peptides and proteins. New peptide ligation strategies, including an asparagine-based ligation and a residue-independent ligation will be developed that exploit the recent discovery of silver-promoted coupling reactions of thioamides. A novel late-stage, chemo-selective assembly of N-glycosylated asparagine residues in peptides and ....Thioamide ligations: new technologies for peptide and protein synthesis. This project aims to develop novel amide-bond forming reactions for the chemical synthesis of peptides and proteins. New peptide ligation strategies, including an asparagine-based ligation and a residue-independent ligation will be developed that exploit the recent discovery of silver-promoted coupling reactions of thioamides. A novel late-stage, chemo-selective assembly of N-glycosylated asparagine residues in peptides and proteins will also be developed. The outcomes of this research will lead to breakthroughs in synthetic methodologies for the assembly and functionalisation of peptides and proteins, thereby enabling access to a range of homogeneous, post translationally modified proteins though total chemical synthesis. These research outcomes will expand Australia's research capability and global competitiveness in the field of biotechnology, delivering significant benefits to the third largest manufacturing sector in Australia.Read moreRead less
Towards the development of orally active antimicrobial peptides with distinctive mode of action. This project aims to design and develop novel antibacterial compounds to address one of humankind's greatest health concerns, that of antibacterial resistance. These will be further modified to make them orally available, thus enhancing their therapeutic and clinical potential.
Novel target of amiloride analogues - picornaviral RNA polymerase. Picornaviruses cause a range of diseases such as poliomyelitis, meningitis, myocarditis, hepatitis A, neonatal sepsis and common cold. No antiviral treatment is available for these infections. Nearly 50% of antiviral drugs used in medicine are viral polymerase inhibitors; however picornaviral RNA polymerase has been largely overlooked as a drug target. We have discovered a group of compounds that inhibit picornaviral RNA polymera ....Novel target of amiloride analogues - picornaviral RNA polymerase. Picornaviruses cause a range of diseases such as poliomyelitis, meningitis, myocarditis, hepatitis A, neonatal sepsis and common cold. No antiviral treatment is available for these infections. Nearly 50% of antiviral drugs used in medicine are viral polymerase inhibitors; however picornaviral RNA polymerase has been largely overlooked as a drug target. We have discovered a group of compounds that inhibit picornaviral RNA polymerase. This project aims to define the inhibition mechanism and to evaluate a potential use of these compounds for antiviral drug development.Read moreRead less
The Role of Amyloid Protein Precursor in Mammalian Copper Transport. The knowledge gained from this investigation will help us to develop new medicines for the treatment of debilitating and ever more prevalent age-related neurodegenerative diseases and will help us to illuminate the role of metals in the ageing process itself. Apart from the obvious economic and social benefits in extending the productive lifetime of its citizens, the outcomes of this project have clear commercial applications. ....The Role of Amyloid Protein Precursor in Mammalian Copper Transport. The knowledge gained from this investigation will help us to develop new medicines for the treatment of debilitating and ever more prevalent age-related neurodegenerative diseases and will help us to illuminate the role of metals in the ageing process itself. Apart from the obvious economic and social benefits in extending the productive lifetime of its citizens, the outcomes of this project have clear commercial applications. We anticipate that there will be patents that will ensue from the programme, which will be licensed to Australian interests, and contribute to the national revenue in the biotechnology and pharmaceutical sector.Read moreRead less
Neural Copper Homeostasis: the role of the Alzheimer Amyloid-beta Precursor Protein. Alzheimer's disease (AD) is creating a growing burden upon Australian medical resources. Copper plays an important role in the development of AD, and drugs designed to adjust brain copper levels are being tested for AD treatment and show therapeutic benefits. This project will determine how copper is involved in AD so that more effective drugs can be developed. Focus will primarily be on copper-binding proteins ....Neural Copper Homeostasis: the role of the Alzheimer Amyloid-beta Precursor Protein. Alzheimer's disease (AD) is creating a growing burden upon Australian medical resources. Copper plays an important role in the development of AD, and drugs designed to adjust brain copper levels are being tested for AD treatment and show therapeutic benefits. This project will determine how copper is involved in AD so that more effective drugs can be developed. Focus will primarily be on copper-binding proteins central to AD, including amyloid-beta, and their role in AD development. Upon completion of this project, we expect to better understand neural copper metabolism in health and in AD pathology, with outcomes directly applicable to therapeutic AD intervention.Read moreRead less
Membrane structure and lipid interactions of the pore-forming toxin Equinatoxin II by NMR. The structure of Equinatoxin II, a pore-forming protein, will be determined in model cell membranes using solid-state NMR spectroscopy. The relationship of molecular structure to bioactivity and the nature of the pore-forming mechanism of this toxin will be determined. The results will aid in understanding how toxins lyse cells and could lead to the design of improved antibiotic peptides. Currently the st ....Membrane structure and lipid interactions of the pore-forming toxin Equinatoxin II by NMR. The structure of Equinatoxin II, a pore-forming protein, will be determined in model cell membranes using solid-state NMR spectroscopy. The relationship of molecular structure to bioactivity and the nature of the pore-forming mechanism of this toxin will be determined. The results will aid in understanding how toxins lyse cells and could lead to the design of improved antibiotic peptides. Currently the structure of membrane proteins are difficult to determine and the newly developed techniques used for the structural determination of this membrane-associated protein will be suitable for studying other membrane proteins and receptors of pharmaceutical importance.Read moreRead less