Discovering novel allosteric probes of muscarinic acetylcholine receptors. This project aims at fostering novel approaches to selectively target vital receptors in the human body, the muscarinic acetylcholine receptors (mAChRs). By harnessing the design of receptor mutations, compounds synthesis and fluorescent imaging, the project expects to develop new pharmacological tools for a family of receptors essential for the life of all vertebrates. By enriching our understanding of this family of rec ....Discovering novel allosteric probes of muscarinic acetylcholine receptors. This project aims at fostering novel approaches to selectively target vital receptors in the human body, the muscarinic acetylcholine receptors (mAChRs). By harnessing the design of receptor mutations, compounds synthesis and fluorescent imaging, the project expects to develop new pharmacological tools for a family of receptors essential for the life of all vertebrates. By enriching our understanding of this family of receptor, the project expects to provide significant benefits to the research field by impacting on future drug discovery efforts, not only at mAChRs, but at other structurally related receptors.Read moreRead less
How lipid binding proteins shape the activity of nuclear hormone receptors. This project aims to explore how a family of lipid binding proteins control organ specific activation of nuclear receptors – receptors that play a key role in generating energy and are critical for life. The project will employ chemical, molecular, cell biology approaches to generate new knowledge about lipid binding protein-receptor interactions and how these complexes dictate receptor activation. The outcomes could pro ....How lipid binding proteins shape the activity of nuclear hormone receptors. This project aims to explore how a family of lipid binding proteins control organ specific activation of nuclear receptors – receptors that play a key role in generating energy and are critical for life. The project will employ chemical, molecular, cell biology approaches to generate new knowledge about lipid binding protein-receptor interactions and how these complexes dictate receptor activation. The outcomes 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. This will benefit the success of drug treatments which require stimulation of a therapeutic response at a target site, and avoidance of potentially toxic activity at other locations.Read moreRead less
The physiological importance of GLP-1R and GIPR dimerisation. Cell surface receptors are vital for relaying information from hormones to the cell to influence cell function, and ultimately physiological responses. Receptors can form oligomers with other receptors, but whether this can influence cellular and physiological responses is not yet defined. This biology-based project aims to bridge this knowledge gap by studying the dimerisation between two related receptors involved in whole body meta ....The physiological importance of GLP-1R and GIPR dimerisation. Cell surface receptors are vital for relaying information from hormones to the cell to influence cell function, and ultimately physiological responses. Receptors can form oligomers with other receptors, but whether this can influence cellular and physiological responses is not yet defined. This biology-based project aims to bridge this knowledge gap by studying the dimerisation between two related receptors involved in whole body metabolic homeostasis. Our team will deliver new knowledge into the disciplines of pharmacology, cellular biology, metabolism and physiology, and provide interdisciplinary research training to students and junior scientists, and strengthen research collaboration within and outside of Australia.Read moreRead less
Probing the role of dynamics in protein modulation of GPCR phenotype . Life relies upon the fundamental ability to convert external stimuli into an appropriate biological response. Such stimuli are transmitted by cell surface proteins (receptors), which convert this stimulus into an intracellular signal. The largest group of cell surface receptors is the G protein-coupled receptor (GPCR) family. Despite advances in GPCR structure determination, many questions regarding the structural basis of GP ....Probing the role of dynamics in protein modulation of GPCR phenotype . Life relies upon the fundamental ability to convert external stimuli into an appropriate biological response. Such stimuli are transmitted by cell surface proteins (receptors), which convert this stimulus into an intracellular signal. The largest group of cell surface receptors is the G protein-coupled receptor (GPCR) family. Despite advances in GPCR structure determination, many questions regarding the structural basis of GPCR function and signalling remain unanswered. The primary outcome of this project is to provide mechanistic insight into the dynamics of GPCR ligand recognition and activation to advance our understanding of GPCR signal transduction, a fundamental biological process for all living organisms.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
Understanding bacteriophage deactivation and stabilisation in formulations. Bacteriophages (phages) are viruses that kill pathogenic bacteria without causing harms to the eco-balance. They can provide a safe and highly effective antimicrobial measure for biocontrol when formulated properly. This project aims to develop a mechanistic understanding of the physicochemical factors responsible for stabilising and deactivating phages in a wide range of formulations. It will create new knowledge on ke ....Understanding bacteriophage deactivation and stabilisation in formulations. Bacteriophages (phages) are viruses that kill pathogenic bacteria without causing harms to the eco-balance. They can provide a safe and highly effective antimicrobial measure for biocontrol when formulated properly. This project aims to develop a mechanistic understanding of the physicochemical factors responsible for stabilising and deactivating phages in a wide range of formulations. It will create new knowledge on key relationships between phage chemistry, phage-excipient interactions and phage stability. The research outcomes would significantly benefit Australia by enabling commercial development in the high value-adding area of environmentally friendly antimicrobial products.Read moreRead less
Structure and dynamics of class B1 G protein coupled receptors . Cells within our body require cell surface proteins (receptors) to convert extracellular stimuli into an appropriate biological response. G protein-coupled receptors are the largest group of cell surface receptors. This project focuses on a subset of these receptors that have diverse and important functions in the central nervous system and the periphery, however there are many unanswered questions regarding the structure of these ....Structure and dynamics of class B1 G protein coupled receptors . Cells within our body require cell surface proteins (receptors) to convert extracellular stimuli into an appropriate biological response. G protein-coupled receptors are the largest group of cell surface receptors. This project focuses on a subset of these receptors that have diverse and important functions in the central nervous system and the periphery, however there are many unanswered questions regarding the structure of these proteins, and how they regulate cellular signalling. The primary outcomes of this project will provide detailed mechanistic insights on how receptors bind their stimuli and how this results in in their activation to mediate fundamental signalling that is important for all living organisms.Read moreRead less