Phage display derived antibody fragments for membrane protein research. Membrane proteins are key components of all living organisms and represent more than 50 per cent of all drug targets. This project will redefine the way membrane proteins are studied and will be highly beneficial to basic research, human disease and the biotechnology industry.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882295
Funder
Australian Research Council
Funding Amount
$225,000.00
Summary
X-ray crystallography resource for membrane proteins and large macromolecular complexes. Structural biology is the underpinning of biotechnology, biopharmaceuticals and rational therapeutic design. The most successful technique for determining the structures of proteins and large macromolecular complexes is x-ray crystallography. This proposal will set up a network of state of the art resources in the Sydney region to capitalise on expertise in these areas. The facilities will foster basic re ....X-ray crystallography resource for membrane proteins and large macromolecular complexes. Structural biology is the underpinning of biotechnology, biopharmaceuticals and rational therapeutic design. The most successful technique for determining the structures of proteins and large macromolecular complexes is x-ray crystallography. This proposal will set up a network of state of the art resources in the Sydney region to capitalise on expertise in these areas. The facilities will foster basic research and collaborations with industry, which will enhance Australia's profile and commercialisation of research. The facility will enhance the usage of the Australian synchrotron, producing flagship projects on the edge of technical possibilities.Read moreRead less
New Treatments For Epitheliod Inflammatory Myofibroblastic Sarcoma
Funder
National Health and Medical Research Council
Funding Amount
$647,267.00
Summary
Epithelioid Inflammatory myofibroblastic sarcoma (eIMS) is a rare aggressive cancer, most common in of childhood and young adults. This cancer has been scarcely studied due to its rarity and is not cured by standard chemotherapeutic regimes. Our investigations will extensively characterise eIMS samples from recently diagnosed patients, and apply a new laboratory model to discover more effective drugs and improve treatment outcomes.
ARC Centre of Excellence in Plant Cell Wall Biology. The ARC Centre for Plant Cell Wall Biology will define the regulatory mechanisms that control molecular, enzymic and cellular processes involved in the synthesis, deposition, re-modelling and depolymerisation of cell wall polysaccharides of cereals and grasses. Plant cell walls represent the world's largest renewable carbon resource, but the regulatory mechanisms responsible for their synthesis and assembly are not understood. Key distinguishi ....ARC Centre of Excellence in Plant Cell Wall Biology. The ARC Centre for Plant Cell Wall Biology will define the regulatory mechanisms that control molecular, enzymic and cellular processes involved in the synthesis, deposition, re-modelling and depolymerisation of cell wall polysaccharides of cereals and grasses. Plant cell walls represent the world's largest renewable carbon resource, but the regulatory mechanisms responsible for their synthesis and assembly are not understood. Key distinguishing features of the Centre will be the international, integrative, and multidisciplinary approach towards addressing major questions in plant biology, its strategy to leverage ARC funding, and its linkages with potential national and international end-users of the fundamental scientific discoveries.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
Phloem unloading of sucrose: cloning, functional characterisation and regulation of novel membrane transporters. Sucrose is the principal form in which plant biomass, produced in photosynthetic leaves, is transported to non-photosynthetic organs for growth and storage. Sucrose transport proteins play pivotal roles in facilitating sucrose transport around plants. Hence activities of sucrose transporters directly impact on plant growth rates and crop yields. Our aim is to isolate hitherto unkno ....Phloem unloading of sucrose: cloning, functional characterisation and regulation of novel membrane transporters. Sucrose is the principal form in which plant biomass, produced in photosynthetic leaves, is transported to non-photosynthetic organs for growth and storage. Sucrose transport proteins play pivotal roles in facilitating sucrose transport around plants. Hence activities of sucrose transporters directly impact on plant growth rates and crop yields. Our aim is to isolate hitherto unknown membrane proteins that move sucrose at high rates between cells and discover their transport properties. Expected outcomes are to better understand mechanisms and regulation of sucrose transport and hence provide novel opportunities to enhance crop yield. The project will foster a productive international collaboration.Read moreRead less