Structure and function of predatory and defensive venoms in cone snails. This project aims to investigate newly-discovered cone snail venoms to accelerate the search for novel bioactive peptides. It was recently discovered that cone snails can rapidly and reversibly switch between distinct venoms in response to predatory or defensive stimuli, implying that defensive and predatory venoms have evolved under separate selection pressures. The project plans to obtain separate predatory and defensive ....Structure and function of predatory and defensive venoms in cone snails. This project aims to investigate newly-discovered cone snail venoms to accelerate the search for novel bioactive peptides. It was recently discovered that cone snails can rapidly and reversibly switch between distinct venoms in response to predatory or defensive stimuli, implying that defensive and predatory venoms have evolved under separate selection pressures. The project plans to obtain separate predatory and defensive venoms and venom duct tissue from individual cone snails to compare and contrast the structure and function of conotoxins evolved for predation versus those evolved for defence, to elucidate the structure and function of these important classes of bioactive peptides.Read moreRead less
Unravelling the molecular diversity and evolution of centipede venoms. The project intends to improve understanding of venom evolution in centipedes. Venoms have emerged as a rich source of pharmacological tools with potential for development into therapeutics and bioinsecticides. However, venoms-based discovery has been limited by the narrow taxonomical range of animals studied, with many groups of venomous animals overlooked. One such group is centipedes, whose venoms contain diverse toxins th ....Unravelling the molecular diversity and evolution of centipede venoms. The project intends to improve understanding of venom evolution in centipedes. Venoms have emerged as a rich source of pharmacological tools with potential for development into therapeutics and bioinsecticides. However, venoms-based discovery has been limited by the narrow taxonomical range of animals studied, with many groups of venomous animals overlooked. One such group is centipedes, whose venoms contain diverse toxins that differ between taxa. This project aims to provide an insight into centipede venom evolution, and how it might be constrained by venom-gland morphology. This study seeks to contribute to our understanding of protein evolution and direct biodiscovery efforts around centipede venom.Read moreRead less
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
Engineering peptides into superglues selective for target proteins. This project aims to discover how to create long-acting peptides for future research tools, drugs, biosensors and diagnostics. Peptides are currently viewed by the general community as injectable performance-enhancing drugs which are difficult to detect because they don't last very long. However, peptides have many potential benefits that are difficult to obtain because of their short durations of action. This project aims to de ....Engineering peptides into superglues selective for target proteins. This project aims to discover how to create long-acting peptides for future research tools, drugs, biosensors and diagnostics. Peptides are currently viewed by the general community as injectable performance-enhancing drugs which are difficult to detect because they don't last very long. However, peptides have many potential benefits that are difficult to obtain because of their short durations of action. This project aims to develop ways of engineering peptide shapes into nanoscale superglues that stick more tightly but selectively to their target proteins, thereby extending their durations of action. Technology for engineering superglues would produce proof of concept and prototypes for future research tools, drugs, diagnostics and biosensors.Read moreRead less
A new source of bivalent molecules from nature. This project aims to describe a new class of naturally occurring multivalent molecules termed secreted cysteine-rich repeat proteins (SCREPs). Multivalency is a key feature of molecular interaction in biology, underlying the high specificity and potency found in many proteins. Focusing on bivalent peptides, the project will generate a database of bioactive SCREPs with similarity to known bioactive peptides, and develop new recombinant methods for t ....A new source of bivalent molecules from nature. This project aims to describe a new class of naturally occurring multivalent molecules termed secreted cysteine-rich repeat proteins (SCREPs). Multivalency is a key feature of molecular interaction in biology, underlying the high specificity and potency found in many proteins. Focusing on bivalent peptides, the project will generate a database of bioactive SCREPs with similarity to known bioactive peptides, and develop new recombinant methods for their production. The project will use advanced nuclear magnetic resonance spectroscopy to characterise members of this new class, providing new insights into the design of bivalent and multivalent peptides and establishing a new source of molecules with applications in the rapidly growing biotechnology sector.Read moreRead less
Decoding the molecular components of aquatic parasite-host interactions. This project aims to further understand the molecular components that regulate aquatic host-parasite interactions which contributes to many diseases worldwide. Aquatic parasites rely on chemical cues to locate and infect their host. This project will target the aquatic host-parasite interaction to decipher these chemical cues, so that future tools may be developed to suppress this interplay. This project expects to contribu ....Decoding the molecular components of aquatic parasite-host interactions. This project aims to further understand the molecular components that regulate aquatic host-parasite interactions which contributes to many diseases worldwide. Aquatic parasites rely on chemical cues to locate and infect their host. This project will target the aquatic host-parasite interaction to decipher these chemical cues, so that future tools may be developed to suppress this interplay. This project expects to contribute imperative basic knowledge for the future control of the intestinal parasite disease, Schistosomiasis, a devastating tropical disease.Read moreRead less
Compressing small peptides for cell absorption. This project aims to understand how to make small structured peptides cell-permeable. Short peptides matching bioactive protein surfaces have no structure in water and do not enter cells, where most biological reactions occur. This project will compress peptides into very small coiled structures and systematically vary cyclic restraints, physicochemical properties and location of components to increase cell uptake by different mechanisms. An expect ....Compressing small peptides for cell absorption. This project aims to understand how to make small structured peptides cell-permeable. Short peptides matching bioactive protein surfaces have no structure in water and do not enter cells, where most biological reactions occur. This project will compress peptides into very small coiled structures and systematically vary cyclic restraints, physicochemical properties and location of components to increase cell uptake by different mechanisms. An expected outcome is new knowledge for predicting structures that make peptides cell-permeable without membrane damage. A new capacity to rationally downsize proteins to small, cell-permeable, structured peptides is anticipated to permit many new biological and industrial applications.Read moreRead less
Engineering Cyclic Peptides For Oral Bioavailability. The 21st century has become the age of injectable peptide therapeutics. To fully realise their benefits , peptide drugs need to become smaller, cheaper and orally deliverable. Proteins often exhibit potent and selective biological actions through small peptide surfaces. These surfaces have been mimicked in cyclic peptides that are similarly potent and selective. However, cyclic peptides do not have the right properties to be oral drugs. This ....Engineering Cyclic Peptides For Oral Bioavailability. The 21st century has become the age of injectable peptide therapeutics. To fully realise their benefits , peptide drugs need to become smaller, cheaper and orally deliverable. Proteins often exhibit potent and selective biological actions through small peptide surfaces. These surfaces have been mimicked in cyclic peptides that are similarly potent and selective. However, cyclic peptides do not have the right properties to be oral drugs. This project aims to re-engineer their surfaces to survive potential degradation in the gut, to permeate membranes and to withstand clearance from blood. The projected outcome of this project is new information and technology for downsizing proteins to small orally bioavailable peptides for therapeutic applications.Read moreRead less
Circular Plant Proteins with Pharmaceutical Applications. The proposed research will develop methods for using plants as protein production factories. Initially I will use plants to create engineered cyclotides that incorporate peptides with proven therapeutic activity against cancer and multiple sclerosis. Successful production of therapeutic proteins in plants will benefit Australians by making treatments for these and other diseases more accessible. It also has the potential for a major econo ....Circular Plant Proteins with Pharmaceutical Applications. The proposed research will develop methods for using plants as protein production factories. Initially I will use plants to create engineered cyclotides that incorporate peptides with proven therapeutic activity against cancer and multiple sclerosis. Successful production of therapeutic proteins in plants will benefit Australians by making treatments for these and other diseases more accessible. It also has the potential for a major economic benefit from the sales of Australian-based drugs. This proposal will also provide outstanding research training for graduate students in multidisciplinary methods that constitute state-of the-art structural and plant molecular biology.Read moreRead less
Novel conotoxins that target ion channels and receptors. This project will discover peptides from cone snail venom that are potential drug candidates. The project will expand our knowledge of these biological active peptides and their mode of action. It will also protect key molecules through patent applications, providing a competitive edge for Australian biotechnology.