Control of actin assembly by cell-cell adhesion: molecular effectors and higher order function. Functional cooperation between the actin cytoskeleton and cadherin cell-cell adhesion molecules plays critical roles during development and morphogenesis. This proposal builds on my lab's recent discovery that E-cadherin interacts with and regulates the Arp2/3 actin nucleator complex, a central determinant of actin assembly in cells. We will explore key implications of this finding, concentrating on d ....Control of actin assembly by cell-cell adhesion: molecular effectors and higher order function. Functional cooperation between the actin cytoskeleton and cadherin cell-cell adhesion molecules plays critical roles during development and morphogenesis. This proposal builds on my lab's recent discovery that E-cadherin interacts with and regulates the Arp2/3 actin nucleator complex, a central determinant of actin assembly in cells. We will explore key implications of this finding, concentrating on defining the molecular mechanisms that regulate Arp2/3 and actin assembly in cadherin-based adhesion. Our work combines molecular characterization of regulatory mechanisms and proteomic searches for new regulators, with tests of the higher-order function of this novel process in cell adhesion and recognition.Read moreRead less
Balancing cadherin-actin cooperation: the key regulatory role of Ena/VASP proteins. This project analyses a fundamental mechanism of how cells work together in tissues. Understanding the fundamental mechanisms of how cells work will provide important basic scientific information to enrich the scientific expertise in Australia and its part in the international community, generate insights relevant for understanding human disease and physical degeneration, and support the training of young scienti ....Balancing cadherin-actin cooperation: the key regulatory role of Ena/VASP proteins. This project analyses a fundamental mechanism of how cells work together in tissues. Understanding the fundamental mechanisms of how cells work will provide important basic scientific information to enrich the scientific expertise in Australia and its part in the international community, generate insights relevant for understanding human disease and physical degeneration, and support the training of young scientists in Australia.Read moreRead less
Nettles & toxic toupees: the molecular weaponry of venomous caterpillars. This project aims to investigate the structure, function and evolution of peptide toxins in venoms made by caterpillars in superfamily Zygaenoidea. Caterpillars in this group are covered in spines that inject pain-causing venoms, and this protects them from vertebrate and invertebrate predators. This project will test if peptides in this venom cause pain by pharmacological modulation of mammalian ion channels and signallin ....Nettles & toxic toupees: the molecular weaponry of venomous caterpillars. This project aims to investigate the structure, function and evolution of peptide toxins in venoms made by caterpillars in superfamily Zygaenoidea. Caterpillars in this group are covered in spines that inject pain-causing venoms, and this protects them from vertebrate and invertebrate predators. This project will test if peptides in this venom cause pain by pharmacological modulation of mammalian ion channels and signalling receptors, and if they have insecticidal properties. The first three-dimensional structures of caterpillar venom peptides will also be solved. Genomes of representatives of two different zygaenoid families will be produced, and genomic techniques will be used to elucidate how venom use evolved at the molecular level.Read moreRead less
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.
Tissue tension homeostasis by junctional mechanosensing. This project examines how tissues use mechanical tension to preserve their integrity. This comes from the recent appreciation that cells pull on the connections between each other to generate tension. Further, molecular mechanisms exist for cells to sense changes in this tension and then to enlist the appropriate responses to restore tension. The project aims to test how local changes in tension are detected and corrected, when tissue inte ....Tissue tension homeostasis by junctional mechanosensing. This project examines how tissues use mechanical tension to preserve their integrity. This comes from the recent appreciation that cells pull on the connections between each other to generate tension. Further, molecular mechanisms exist for cells to sense changes in this tension and then to enlist the appropriate responses to restore tension. The project aims to test how local changes in tension are detected and corrected, when tissue integrity is compromised by very different causes. The project endeavours to establish a new conceptual paradigm for understanding tissue homeostasis, based on cell biology and biomechanics, with implications for developmental biology and tissue engineering.Read moreRead less
Versatile elastin based hybrid hydrogels for chondrocyte transplantation and repair. Cartilage repair is often limited after significant trauma, sports injury and disease. This project will generate a new family of hybrid biomaterials constructed by precisely blending natural and synthetic components. These novel biomaterials will establish the foundation for manufactured prefabrication and in situ injection to promote healing.
Probing the four photosynthetic membrane protein complexes at work in situ in leaves. This proposal aims at sustainable improvements in plant productivity and photosynthetic adaptation in drastic Australian climates. In photosynthesis, membranes with the four multiprotein complexes use sunlight to make compounds that drive carbon assimilation. Instead of the usual dissection of photosynthetic membranes, this project will develop and refine the applicant's rapid, reliable, non-intrusive technique ....Probing the four photosynthetic membrane protein complexes at work in situ in leaves. This proposal aims at sustainable improvements in plant productivity and photosynthetic adaptation in drastic Australian climates. In photosynthesis, membranes with the four multiprotein complexes use sunlight to make compounds that drive carbon assimilation. Instead of the usual dissection of photosynthetic membranes, this project will develop and refine the applicant's rapid, reliable, non-intrusive techniques to probe the four membrane complexes at work in their native state in leaves. Two portable commercial instruments will potentially emerge from the techniques. This novel non-reductionist approach will identify key limitations to photosynthetic performance under stress, and insights into improvements for primary plant productivity.Read moreRead less
Does a novel class of small RNA molecules control self-incompatibility in solanaceous plants? Self-incompatibility is a simple and genetically defined cell recognition system that prevents inbreeding in many plant species. Flowers of self-incompatible plants can distinguish self pollen from foreign pollen, and allow only foreign pollen to fertilise their egg cells. This proposal will investigate the possibility that the part of the genetic self-incompatibility locus controlling recognition of ....Does a novel class of small RNA molecules control self-incompatibility in solanaceous plants? Self-incompatibility is a simple and genetically defined cell recognition system that prevents inbreeding in many plant species. Flowers of self-incompatible plants can distinguish self pollen from foreign pollen, and allow only foreign pollen to fertilise their egg cells. This proposal will investigate the possibility that the part of the genetic self-incompatibility locus controlling recognition of pollen is a novel type of gene that encodes a small RNA molecule but no protein. Knowledge gained by studying the self-incompatibility genes will help us to understand how plant cells recognise each other, and may allow us to manipulate seed (and hence crop) production.Read moreRead less
Understanding the molecular mechanisms regulating neuronal fusion. Neurons are tightly connected individual cells that communicate through chemical and electrical signals, and this project aims to discover the key molecules that allow these cells to remain as individual units without fusing with each other. The nervous system, unlike other tissues, is made of discrete individual cells, connected by chemical and electrical synapses but not by cytoplasmic continuity. However, how this is achieved ....Understanding the molecular mechanisms regulating neuronal fusion. Neurons are tightly connected individual cells that communicate through chemical and electrical signals, and this project aims to discover the key molecules that allow these cells to remain as individual units without fusing with each other. The nervous system, unlike other tissues, is made of discrete individual cells, connected by chemical and electrical synapses but not by cytoplasmic continuity. However, how this is achieved and how neurons maintain their individuality during development, remodelling and ageing is unknown. The project aims to address this gap using a genetic approach and the nematode Caenorhabditis elegans as an experimental system. The results may provide insights into how the nervous system develops and functions.Read moreRead less
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