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.
Force Fields for Structure Refinement and Computational Drug Design. The ability to model molecular systems at an atomic level, as used in protein structure refinement or computational drug design, is critically dependent on the accuracy with which inter-atomic interactions are represented. Highly optimised and well-validated interaction parameters are available for common biomolecules, such as amino acids, sugars and lipids, but not for co-factors, substrates and potential drug molecules, or ot ....Force Fields for Structure Refinement and Computational Drug Design. The ability to model molecular systems at an atomic level, as used in protein structure refinement or computational drug design, is critically dependent on the accuracy with which inter-atomic interactions are represented. Highly optimised and well-validated interaction parameters are available for common biomolecules, such as amino acids, sugars and lipids, but not for co-factors, substrates and potential drug molecules, or other molecules of interest such as polymers and dendrimers. The aim of this project is to develop and validate geometric and interaction parameters (force fields) for complex organic molecules and use these to facilitate bio-molecular structure refinement and computational drug design.Read moreRead less
Improving empirical force fields: a big-data approach. This project aims to improve the ability to represent the thermodynamic properties of molecules of biological, pharmaceutical or materials interest by developing force fields capable of describing a diverse range of molecules both consistently and with high fidelity. The project aims to exploit a rapidly expanding, in-house database of parameterized molecular structures to develop highly optimised, well-validated parameters that are both con ....Improving empirical force fields: a big-data approach. This project aims to improve the ability to represent the thermodynamic properties of molecules of biological, pharmaceutical or materials interest by developing force fields capable of describing a diverse range of molecules both consistently and with high fidelity. The project aims to exploit a rapidly expanding, in-house database of parameterized molecular structures to develop highly optimised, well-validated parameters that are both consistent and transferable, enabling molecules of any size or complexity to be parameterised with a fidelity currently only possible for simple organics. This will provide significant benefits, such as helping to improve the accuracy and reliability of ligand: protein complexes determined experimentally, a limiting factor in computational drug design.Read moreRead less
Theoretical modelling and design of safe covalent anti-cancer drugs. Covalent drugs are a new class of drugs with outstanding potential in cancer therapy. Detailed computer modelling studies will be performed to determine how these drugs interact with an important target in cancer therapy, the epithelial growth factor receptor, and thereby aid the development of new cancer treatments.
Bioactive Peptides as Pharmacological Tools and Novel Drug Leads. Bioactive peptides are produced by all organisms and play numerous critical physiological roles, including in cellular communication, host defence and capture of prey. Peptides have huge potential as tools for studying roles of signalling pathways and as novel drugs due to their high affinity and selectivity for various therapeutically relevant targets. However their use has been limited by poor in vivo stability. This project is ....Bioactive Peptides as Pharmacological Tools and Novel Drug Leads. Bioactive peptides are produced by all organisms and play numerous critical physiological roles, including in cellular communication, host defence and capture of prey. Peptides have huge potential as tools for studying roles of signalling pathways and as novel drugs due to their high affinity and selectivity for various therapeutically relevant targets. However their use has been limited by poor in vivo stability. This project is focused on studying structural features of a range of peptides and their contributions to both activity and to resistance against degradation, with the aim to develop stabilised bioactive peptide sequences for in vivo applications, allowing the full potential of peptides as drugs to be realised.Read moreRead less
The mechanism of membrane disruption by antimicrobial peptides. Bacterial resistance to antibiotics is a growing crisis in modern medicine. Antibacterial peptides from Australian frogs represent a new class of potent and selective antibacterial agents. Understanding how these peptides kill bacteria but not vertebrate cells could lead to the design of new drugs for pharmaceutical and/or clinical purposes.
Industrial Transformation Training Centres - Grant ID: IC180100021
Funder
Australian Research Council
Funding Amount
$4,163,359.00
Summary
ARC Training Centre for the Development of Tools for Fragment Based Design. The ARC Training Centre for the Development of Tools for Fragment Based Design aims to inspire the next generation of drug discovery research leaders. It plans to provide direct experience with industry partners, training and master classes in early stage drug-discovery from industry experts. The Centre is expected to accelerate research translation and industry engagement by providing an efficient strategy for the scree ....ARC Training Centre for the Development of Tools for Fragment Based Design. The ARC Training Centre for the Development of Tools for Fragment Based Design aims to inspire the next generation of drug discovery research leaders. It plans to provide direct experience with industry partners, training and master classes in early stage drug-discovery from industry experts. The Centre is expected to accelerate research translation and industry engagement by providing an efficient strategy for the screening of a biological target and early medicinal chemistry for optimisation. The expected outcome of the Centre is to equip the trainees with the skills to make key contributions to the sustainability and growth of the sector and to provide significant capacity to address global challenges for 21st century pharmaceutical innovation.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100067
Funder
Australian Research Council
Funding Amount
$390,000.00
Summary
The Vevo 2100 Micro-ultrasound plus LAZR Photoacoustic Imaging Platform . The Vevo 2100 micro-ultrasound plus LAZR photoacoustic imaging platform: The Vevo/LAZR ultrasound/photoacoustic imaging facility will allow researchers to achieve multiple outcomes: to visualise and quantify, non-invasively, tissue and molecular structures; the movement and behaviour of cells; and the delivery patterns of administered imaging dyes and nanoparticles in mouse models and reconstructed tissues. This will enabl ....The Vevo 2100 Micro-ultrasound plus LAZR Photoacoustic Imaging Platform . The Vevo 2100 micro-ultrasound plus LAZR photoacoustic imaging platform: The Vevo/LAZR ultrasound/photoacoustic imaging facility will allow researchers to achieve multiple outcomes: to visualise and quantify, non-invasively, tissue and molecular structures; the movement and behaviour of cells; and the delivery patterns of administered imaging dyes and nanoparticles in mouse models and reconstructed tissues. This will enable researchers to obtain anatomical, functional, physiological and molecular data simultaneously and in real-time, with resolution down to 40 micrometres. This will translate into both user efficiency and laboratory cost effectiveness, but more significantly is expected to result in greater understanding of fundamental mechanisms regulating the body's cell and tissue functions.Read moreRead less
Making peptides orally bioavailable. Bioactive peptides are exceptionally useful molecules, however to fully realise their exciting applications key limitations need to be overcome: they can't be delivered orally and they do not last long in the body. This project aims to develop a molecular tag that can dramatically enhance both the oral absorption and time in the body of a peptide. This will include identifying the key elements of the tag required for function, the breadth of peptide cargoes i ....Making peptides orally bioavailable. Bioactive peptides are exceptionally useful molecules, however to fully realise their exciting applications key limitations need to be overcome: they can't be delivered orally and they do not last long in the body. This project aims to develop a molecular tag that can dramatically enhance both the oral absorption and time in the body of a peptide. This will include identifying the key elements of the tag required for function, the breadth of peptide cargoes it can be applied to and the mechanisms underlying this technology. The outcomes of this project will facilitate the future development of peptides for biotechnology, pharmaceutical and veterinary applications.Read moreRead less
Exploring the novel structural features of influenza virus sialidase. The outcomes of this project will provide a deeper mechanistic understanding of influenza virus sialidase and the importance of the enzyme's flexible loops in carbohydrate recognition. Specifically, this project will improve our understanding of fundamental aspects of inhibitor binding by influenza virus sialidases.