Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100118
Funder
Australian Research Council
Funding Amount
$600,000.00
Summary
Nuclear magnetic resonance spectroscopy facilities for the Sydney region. The determination of molecular structure is crucial in the chemical and biomolecular sciences, leading to the development of new drugs and other types of molecules and providing an understanding of how molecules interact with each other. The requested equipment will provide the ability for researchers in the Sydney region to advance our knowledge at this fundamental level by expanding the number and types of experiments th ....Nuclear magnetic resonance spectroscopy facilities for the Sydney region. The determination of molecular structure is crucial in the chemical and biomolecular sciences, leading to the development of new drugs and other types of molecules and providing an understanding of how molecules interact with each other. The requested equipment will provide the ability for researchers in the Sydney region to advance our knowledge at this fundamental level by expanding the number and types of experiments that can be performed.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100135
Funder
Australian Research Council
Funding Amount
$700,000.00
Summary
Federated single crystal X-ray structural analysis facility. X-ray crystallography is the most widely applied method for the determination of three-dimensional molecular structures. These structures range in size from small systems such as materials and pharmaceuticals through to large biological structures such as proteins. This application will provide a multidisciplinary facility covering the structural characterisation needs of chemistry, pharmacy, biology, and medicine. This will position l ....Federated single crystal X-ray structural analysis facility. X-ray crystallography is the most widely applied method for the determination of three-dimensional molecular structures. These structures range in size from small systems such as materials and pharmaceuticals through to large biological structures such as proteins. This application will provide a multidisciplinary facility covering the structural characterisation needs of chemistry, pharmacy, biology, and medicine. This will position local universities for key scientific breakthroughs that benefit the Australian community by providing improved healthcare technologies, and processes. Furthermore, access to this world-class facility will provide state-of-the-art training for undergraduate, postgraduate and postdoctoral researchers.Read moreRead less
The role of low-energy excited states in solar-energy capture. This project aims to determine the nature and role of the lowest-energy excited states in most natural photosynthetic reaction centres and light-harvesting complexes. The lowest-energy states of bacterial reaction centres are critical to function and are used as a paradigm in artificial organic solar-energy capture, but for most photosystems their nature remains unknown. The project aims to answer the critical question of why they do ....The role of low-energy excited states in solar-energy capture. This project aims to determine the nature and role of the lowest-energy excited states in most natural photosynthetic reaction centres and light-harvesting complexes. The lowest-energy states of bacterial reaction centres are critical to function and are used as a paradigm in artificial organic solar-energy capture, but for most photosystems their nature remains unknown. The project aims to answer the critical question of why they do not actually prevent function. It is expected that both the outcomes obtained and techniques developed will be directly relevant to solar-energy device design. The project will apply five existing, complimentary and purposely built spectrometers as well as quantum electronic and nuclear simulation techniques to identify and characterise three key systems.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100026
Funder
Australian Research Council
Funding Amount
$178,839.00
Summary
Ultrafast magic angle spinning solid-state nuclear magnetic resonance capability. This project aims to extend an existing nuclear magnetic resonance (NMR) spectrometer for structural investigations of proteins in the solid state. Many proteins, such as amyloids and flexible proteins, cannot be studied by X-ray crystallography, solution NMR spectroscopy or cryoelectron microscopy, because they cannot be crystallised or are not sufficiently soluble, or are structurally too heterogeneous. This proj ....Ultrafast magic angle spinning solid-state nuclear magnetic resonance capability. This project aims to extend an existing nuclear magnetic resonance (NMR) spectrometer for structural investigations of proteins in the solid state. Many proteins, such as amyloids and flexible proteins, cannot be studied by X-ray crystallography, solution NMR spectroscopy or cryoelectron microscopy, because they cannot be crystallised or are not sufficiently soluble, or are structurally too heterogeneous. This project will extend the capability of an existing 800 MHz NMR spectrometer to solid-state NMR. By offering ultrafast magic angle spinning speeds, the system aims to afford greatly enhanced sensitivity and multidimensional NMR spectra of protein systems not previously amenable to structural analysis by NMR spectroscopy or other techniques. This will have important applications in biotechnology and biomedicine.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160100608
Funder
Australian Research Council
Funding Amount
$359,000.00
Summary
Investigating the structural basis of human antibody stability. This project plans to use protein engineering and X-ray crystallography to investigate the effects of stabilising mutations on antigen binding and the antibody-antigen interaction. Monoclonal antibodies are high-affinity reagents that have transformed the study of biological processes. However, antibodies often display inherent instability, which limits applicability. Mutations have recently been identified that render human antibod ....Investigating the structural basis of human antibody stability. This project plans to use protein engineering and X-ray crystallography to investigate the effects of stabilising mutations on antigen binding and the antibody-antigen interaction. Monoclonal antibodies are high-affinity reagents that have transformed the study of biological processes. However, antibodies often display inherent instability, which limits applicability. Mutations have recently been identified that render human antibodies resistant to aggregation. Preliminary data indicates that stabilising mutations improves the biophysical properties of monoclonals without affecting the native antibody structure. The project aims to provide detailed insights into the molecular basis of antibody stability.Read moreRead less
Investigating the dynamic nature of antibody stability. The aim of the project is to provide insights into the molecular mechanisms of antibody stability. Monoclonal antibodies have transformed the study of biological processes and represent blockbuster therapeutics for cancer and inflammation. Unfortunately, antibodies often display limited stability, which greatly hinders development. Mutations have recently been identified that render human antibodies resistant to aggregation, and high-resolu ....Investigating the dynamic nature of antibody stability. The aim of the project is to provide insights into the molecular mechanisms of antibody stability. Monoclonal antibodies have transformed the study of biological processes and represent blockbuster therapeutics for cancer and inflammation. Unfortunately, antibodies often display limited stability, which greatly hinders development. Mutations have recently been identified that render human antibodies resistant to aggregation, and high-resolution crystal structures are being used to identify function. Intriguingly, preliminary data indicates that the mutations do not affect the native antibody structure, but rather influence dynamic states. The project plans to use a combination of mutagenesis, molecular dynamics simulation and deuterium exchange to study antibody dynamics.Read moreRead less
Structural studies of a reconstructed primordial antigen receptor. Antigen receptors (B- and T-cell receptor) form the basis of the adaptive immune system of humans and all other modern day vertebrates. These complex receptors are believed to have evolved from an extinct homodimeric (symmetrical) ancestor through a process of gene duplication and diversification. However, any molecular insights had so far remained elusive. Using laboratory evolution and X-ray crystallography this project demonst ....Structural studies of a reconstructed primordial antigen receptor. Antigen receptors (B- and T-cell receptor) form the basis of the adaptive immune system of humans and all other modern day vertebrates. These complex receptors are believed to have evolved from an extinct homodimeric (symmetrical) ancestor through a process of gene duplication and diversification. However, any molecular insights had so far remained elusive. Using laboratory evolution and X-ray crystallography this project demonstrates that such a primordial receptor can in principle be reconstructed and characterised. The project proposes to expand this work, which will provide intriguing insights into antigen receptor evolution. The reconstruction of basic recognition modules will also be highly beneficial for biosensor applications. Read moreRead less
Artificially building the bacterial flagellar motor. This project will allow us to learn how nature’s most sophisticated rotary motor works and how to build these artificially, establishing a new field of research into man-made biological machines. This has potential applications for the emerging field of nanotechnology to make nanometre-scale devices that are powered by efficient biological machines.