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Expanding The Repertoire Of Immunomodulatory Drugs: Targeting The Melanocortin System Using Engineered Cyclic Peptides
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Autoimmune diseases, including rheumatoid arthritis and psoriasis, have profound impacts on the lives of many Australians. New drugs are required for these diseases as existing treatments are expensive, become less effective with repeated use or cause adverse side effects. My project will work towards addressing this need by investigating the potential of ultrastable cyclic miniproteins as scaffolds for displaying bioactive peptides that are known to restore immune self-tolerance.
Modulating Protein-Protein Interactions In Disease
Funder
National Health and Medical Research Council
Funding Amount
$863,910.00
Summary
Most diseases are driven by protein-protein interactions often with few/no greasy pockets to fit small molecule drugs. Innovative approaches to new drugs are needed for these proteins. This project combines chemistry, biochemistry and pharmacology to create new drug leads, new knowledge on drug action and disease development at gene, protein, cell, animal levels, and aims to trial new drug leads in preclinical and eventually clinical tests in inflammatory and metabolic diseases, pain and cancer.
This research draws together my expertise in medicinal chemistry, biochemistry, pharmacology and virology to design and develop new compounds that we can use to interrogate and regulate human and viral proteins that cause disease. Protein, cell and animal studies relevant to major 21st century health burdens (such as inflammatory, infectious and metabolic diseases, cancer, pain and viral infections) will provide important new information on mechanisms of disease development and drug action.
Gain from pain: new tools from venomous animals for exploring pain pathways. This project aims to explore animal venoms for new pain-causing toxins, to determine their structure and mechanism of action. Many venomous animals use their venom defensively and envenomation is frequently associated with rapid and often excruciating pain. In most cases the molecular mechanisms by which they achieve this is unknown. Using biochemical, pharmacological and biophysical techniques, this project expects to ....Gain from pain: new tools from venomous animals for exploring pain pathways. This project aims to explore animal venoms for new pain-causing toxins, to determine their structure and mechanism of action. Many venomous animals use their venom defensively and envenomation is frequently associated with rapid and often excruciating pain. In most cases the molecular mechanisms by which they achieve this is unknown. Using biochemical, pharmacological and biophysical techniques, this project expects to uncover toxins that employ new mechanisms of pain signalling, leading to new insights into pain physiology.Read moreRead less
Toxins from Down Under: Novel tools to understand and modulate ion channels. Venoms are complex secretions containing biologically active components that have evolved over millions of years to specifically target the nervous systems of predators and prey. Two novel classes of toxins from snake and plant venoms that act on voltage-gated sodium channels, key proteins that regulate neuronal excitability, were recently identified by the research team. The project aims to develop and apply state-of-t ....Toxins from Down Under: Novel tools to understand and modulate ion channels. Venoms are complex secretions containing biologically active components that have evolved over millions of years to specifically target the nervous systems of predators and prey. Two novel classes of toxins from snake and plant venoms that act on voltage-gated sodium channels, key proteins that regulate neuronal excitability, were recently identified by the research team. The project aims to develop and apply state-of-the-art chemical, structural and biological techniques to unravel the molecular mechanisms through which these novel toxin classes act at their targets. Insights gained from this project will help identify and develop novel channel-modulating molecules that may have applications as neuroscience tools, diagnostics or drugs.Read moreRead less
The potential of membranes – peptide engineering to modulate ion channels. This project aims to develop a platform technology to identify new and selective sodium channel inhibitors based on ultra-stable venom peptides that can interact with and cross membranes. Sodium channels are involved in almost all aspects of human physiology. The ability to selectively inhibit individual sodium channel subtypes and to understand what drives peptides' ability to cross membranes would be a major achievement ....The potential of membranes – peptide engineering to modulate ion channels. This project aims to develop a platform technology to identify new and selective sodium channel inhibitors based on ultra-stable venom peptides that can interact with and cross membranes. Sodium channels are involved in almost all aspects of human physiology. The ability to selectively inhibit individual sodium channel subtypes and to understand what drives peptides' ability to cross membranes would be a major achievement and lead to new neuroscience research tools and technologies. This project’s proposed technology could be translated into new knowledge relevant to the biotechnology industry.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE150100784
Funder
Australian Research Council
Funding Amount
$373,254.00
Summary
Molecular probe development for the oxytocin and vasopressin receptors. The oxytocin and vasopressin receptors are part of a 600 million year old signalling system that is widely distributed in the kingdom of life. It is involved in many fundamental physiological functions, however we still lack a complete toolbox of selective probes to delineate the individual receptor subtypes. This project aims to introduce a novel and innovative strategy that uses state-of-the art discovery techniques to ide ....Molecular probe development for the oxytocin and vasopressin receptors. The oxytocin and vasopressin receptors are part of a 600 million year old signalling system that is widely distributed in the kingdom of life. It is involved in many fundamental physiological functions, however we still lack a complete toolbox of selective probes to delineate the individual receptor subtypes. This project aims to introduce a novel and innovative strategy that uses state-of-the art discovery techniques to identify selective ligands in nature. Leads will be developed into molecular probes to facilitate in-depth studies of this system. This strategy is applicable to other systems and the outcomes will contribute to a significant advancement of knowledge in chemical biology.Read moreRead less
Breaching membrane barriers. This project will endeavour to develop novel molecular transporters to deliver macromolecules inside cells or microorganisms. Cell membranes are barriers to macromolecules. The ability to cross these barriers and deliver biological macromolecules into cells represents a major achievement with endless opportunities to modulate pathways and to introduce biomarkers, therapeutics and research tools. The project’s novel platform technology would be based on stable cyclic ....Breaching membrane barriers. This project will endeavour to develop novel molecular transporters to deliver macromolecules inside cells or microorganisms. Cell membranes are barriers to macromolecules. The ability to cross these barriers and deliver biological macromolecules into cells represents a major achievement with endless opportunities to modulate pathways and to introduce biomarkers, therapeutics and research tools. The project’s novel platform technology would be based on stable cyclic peptides to deliver genes, proteins, probes or biomarkers into distinct cell types that can monitor or modulate specific pathways and be translated into new knowledge and specific industrial applications.Read moreRead less
Understanding sub-cellular systems at the atomic level. By extending the range of biomolecular systems that can be modelled computationally at the atomic level the project will enable important biomedical processes such as how bacterial toxins penetrate cell membranes and how protein hormones transmit signals into cells to be understood in unprecedented detail.