Surface Forces in Aqueous Electrolytes. This project studies the force between two nearby colloidal particles or macromolecules in aqueous electrolyte solutions. Although such forces control the approach and binding of particles in electrolytes and hence have large practical significance they are poorly known. In recent work I established a rigorous scheme for calculation of the electrostatic contribution to the force and proved its feasibility. In order to realise practical applications, such a ....Surface Forces in Aqueous Electrolytes. This project studies the force between two nearby colloidal particles or macromolecules in aqueous electrolyte solutions. Although such forces control the approach and binding of particles in electrolytes and hence have large practical significance they are poorly known. In recent work I established a rigorous scheme for calculation of the electrostatic contribution to the force and proved its feasibility. In order to realise practical applications, such as in drug design, we must know the mean force between an ion and a surface or functional surface group. Here I propose to perform the required simulations and explore the analytical simplifications.Read moreRead less
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
Preparation of Photo-Affinity Molecular Probes for the Identification of Gibberellin Receptors. Bioactive gibberellins affect numerous processes during plant growth and development, including seed germination, leaf expansion, stem elongation, flowering and fruit development. However, only very limited information is available regarding their mode of action at the molecular level. The central aim of the project is to prepare a family of photo-affinity molecular probes based on the gibberellin m ....Preparation of Photo-Affinity Molecular Probes for the Identification of Gibberellin Receptors. Bioactive gibberellins affect numerous processes during plant growth and development, including seed germination, leaf expansion, stem elongation, flowering and fruit development. However, only very limited information is available regarding their mode of action at the molecular level. The central aim of the project is to prepare a family of photo-affinity molecular probes based on the gibberellin molecule that will be designed to provide critical information on the location and structure of gibberellin receptors. Screening of the probes for potential effectiveness will be determined initially by the measurement of alpha-amylase produced in a standard barley aleurone assay.Read moreRead less
A hierarchical quantum mechanical and classical simulation of biological ion channels. I aim to develop a methodology incorporating molecular quantum
mechanics and classical Brownian mechanics in a way that can be
applied practically to large macromolecular systems, thus relating
fine structural details to experimentally measurable
properties. Specifically, I will apply this methodology to study ion
channels in which the challenge is to relate electronic and atomic
structure to the conduct ....A hierarchical quantum mechanical and classical simulation of biological ion channels. I aim to develop a methodology incorporating molecular quantum
mechanics and classical Brownian mechanics in a way that can be
applied practically to large macromolecular systems, thus relating
fine structural details to experimentally measurable
properties. Specifically, I will apply this methodology to study ion
channels in which the challenge is to relate electronic and atomic
structure to the conductance properties of the channel. Accurately
determining these relationships provides a pathway to developing cures
for many neurological, cardiac, and muscular diseases.
Read moreRead less
Platelet Glycoprotein Proteolysis: Novel Mechanisms And Risk Factors
Funder
National Health and Medical Research Council
Funding Amount
$441,473.00
Summary
Platelets are the richest source of amyloid precursor protein (APP) in the body. Platelet ADAM10 regulates both the expression and function of the major platelet collagen receptor GPVI, and protective APP processing. Coagulation protein Factor X has a role in activation of ADAM10. This activation is disrupted in blood that has been treated with direct oral anticoagulant (DOAC) rivaroxaban. This grant will investigate the implications for people taking rivaroxaban on regulation of APP and GPVI.
Asymmetric Synthesis of Chiral Phosphines, Arsines, and Stibines. There are now chiral phosphine-transition metal catalysts that rival enzymes in their efficiency for the asymmetric synthesis of important chiral drugs, fragrants, cosmetics, nutrients, vitamins, and pesticides. This project is aimed at a generalised asymmetric synthesis of the critical components of these enzyme mimics, notably enantiopure chiral phosphines, but also chiral arsines and stibines, by a highly innovative approach t ....Asymmetric Synthesis of Chiral Phosphines, Arsines, and Stibines. There are now chiral phosphine-transition metal catalysts that rival enzymes in their efficiency for the asymmetric synthesis of important chiral drugs, fragrants, cosmetics, nutrients, vitamins, and pesticides. This project is aimed at a generalised asymmetric synthesis of the critical components of these enzyme mimics, notably enantiopure chiral phosphines, but also chiral arsines and stibines, by a highly innovative approach that involves novel six-electron phosphenium, arsenium, and stibinium cations that are themselves stabilised by chiral phosphines so that chemical breeder reactions are possible. The use of chiral auxiliaries from the natural pool and from biotechnology will also be investigated.Read moreRead less
Quantum-chemical design of stereoregular polyphosphines for nanowires. In this project we will be designing and producing stereoregular polyphosphines that can self-assemble gold and silver complexes that mimic the molecular architectures of DNA and certain proteins. The longer gold complexes will behave as insulated nanowires, and are an exciting prospect for the development of nanotechnological devices. The shorter silver and gold complexes are expected to have significant antitumour propertie ....Quantum-chemical design of stereoregular polyphosphines for nanowires. In this project we will be designing and producing stereoregular polyphosphines that can self-assemble gold and silver complexes that mimic the molecular architectures of DNA and certain proteins. The longer gold complexes will behave as insulated nanowires, and are an exciting prospect for the development of nanotechnological devices. The shorter silver and gold complexes are expected to have significant antitumour properties. This project, which will use a unique theoretical-experimental approach to design the stereoregular polyphosphines, will enhance Australia's international scientific reputation, and will contribute to technological advancement in the national priority areas of nanotechnology and biotechnology.Read moreRead less
Towards Nano-circuits: 2 and 3-Dimensional Carbon-Wired Nano-architectures. Whilst Australia has a world-class profile in organotransition metal chemistry, main-group chemistry is under-represented, despite the enormous technological importance of materials based on these elements. In addition to the fundamental breakthrough science to be explored, the project will provide a training vehicle for 5 young scientists in both main group and organometallic chemistry. The target compounds involve an e ....Towards Nano-circuits: 2 and 3-Dimensional Carbon-Wired Nano-architectures. Whilst Australia has a world-class profile in organotransition metal chemistry, main-group chemistry is under-represented, despite the enormous technological importance of materials based on these elements. In addition to the fundamental breakthrough science to be explored, the project will provide a training vehicle for 5 young scientists in both main group and organometallic chemistry. The target compounds involve an essentially unique marriage of the fields of main-group and transition metal chemistry to provide complex nano-architectures based on the modular interconnection of metals and non-metals by carbon wires at the molecular level - nanoscopic counterparts of macroscopic circuit components.Read moreRead less
Understanding and Harnessing the Unique and Curious Metal Boron Bond: Unlocking the Metallaboratrane Cage. Metal-boron bonding holds enormous technological importance due to the emergence of boron-based metal-mediated synthetic transformations that access a diversity of high value-added fine chemicals. Whilst Australia boasts an emergent boron-based fine chemicals industry, no research program into the nature of metal boron bonding exists to provide either fundamental science or advanced trainin ....Understanding and Harnessing the Unique and Curious Metal Boron Bond: Unlocking the Metallaboratrane Cage. Metal-boron bonding holds enormous technological importance due to the emergence of boron-based metal-mediated synthetic transformations that access a diversity of high value-added fine chemicals. Whilst Australia boasts an emergent boron-based fine chemicals industry, no research program into the nature of metal boron bonding exists to provide either fundamental science or advanced training in organometallic boron chemistry. The proposed work offers two distinct national benefits: The maintenance of a discipline in which Australia leads the world (metallaboratranes) and the genesis of one, which whilst intensely studied elsewhere, is notably absent from the Australian science base (low coordinate, unsaturated boron chemistry).Read moreRead less
Supramolecular Rip-n-Sew - New Computational Tools for Modelling Supermolecules. This project will develop new computational tools for predicting the chemical behaviour of large molecular and supramolecular systems with an accuracy and efficiency that has not previously been possible. It will also increase our mechanistic understanding of the principles governing supramolecular assembly in chemical and biological systems. This will enable cost and time savings in the design of advanced material ....Supramolecular Rip-n-Sew - New Computational Tools for Modelling Supermolecules. This project will develop new computational tools for predicting the chemical behaviour of large molecular and supramolecular systems with an accuracy and efficiency that has not previously been possible. It will also increase our mechanistic understanding of the principles governing supramolecular assembly in chemical and biological systems. This will enable cost and time savings in the design of advanced materials in the medical and agricultural contexts.Read moreRead less