Early evolutionary origins of mechanosensory transduction: structure, function and phylogenetic studies of the family of mechanosensitive channels in cell-walled organisms. The proposed project is based on the recent progress the applicants have made by (i) identifying a novel family of mechanosensitive (MS) channels in cell-walled organisms, which include Archaea and Bacteria (prokaryotes), as well as fungi and plants (eukaryotes), and (ii) determining basic aspects of the structural dynamics ....Early evolutionary origins of mechanosensory transduction: structure, function and phylogenetic studies of the family of mechanosensitive channels in cell-walled organisms. The proposed project is based on the recent progress the applicants have made by (i) identifying a novel family of mechanosensitive (MS) channels in cell-walled organisms, which include Archaea and Bacteria (prokaryotes), as well as fungi and plants (eukaryotes), and (ii) determining basic aspects of the structural dynamics of MscL, the prototype MS channel, using electronparamagnetic resonance spectroscopy and molecular dynamics simulations in combination with the patch clamp technique. The aim of the project is to elucidate the molecular principles underlying the function of MS channels, which is of fundamental importance for understanding of the biophysics and physiology of mechanosensory transduction throughout the biological world.Read moreRead less
Force from lipids: the role of the lipid bilayer in mechanosensory transduction. The proposed research will significantly contribute to a better understanding of the wide range of physiological processes underlying mechanosensory transduction in living cells. The direct benefit for Australian science consists of: (i) strengthening international links with leading overseas laboratories, and (ii) accessing the state-of-the-art expertise not available in Australia. The acquired knowledge will aid i ....Force from lipids: the role of the lipid bilayer in mechanosensory transduction. The proposed research will significantly contribute to a better understanding of the wide range of physiological processes underlying mechanosensory transduction in living cells. The direct benefit for Australian science consists of: (i) strengthening international links with leading overseas laboratories, and (ii) accessing the state-of-the-art expertise not available in Australia. The acquired knowledge will aid in developing and designing artificial tactile sensors inspired by their biological models studied in this project. Long-term, the project is expected to make an original contribution towards developing new technologies and novel medical applications, both of which promise to be of great national benefit.Read moreRead less
Novel Mass Spectrometric Approaches to the Study of Protein-Protein Interactions. Protein-protein interactions mediate all fundamental cellular processes, yet the structural complexity of protein assemblies mean they are often difficult to characterise using traditional analytical methods. This project will develop and demonstrate novel mass spectrometric approaches towards a molecular level description of the structure and interactions of biological protein complexes, which in turn may underpi ....Novel Mass Spectrometric Approaches to the Study of Protein-Protein Interactions. Protein-protein interactions mediate all fundamental cellular processes, yet the structural complexity of protein assemblies mean they are often difficult to characterise using traditional analytical methods. This project will develop and demonstrate novel mass spectrometric approaches towards a molecular level description of the structure and interactions of biological protein complexes, which in turn may underpin the rational design of drugs for the treatment of a range of human health conditions. This project will also provide training of young researchers to the highest international standards in mass spectrometry and protein science, for benefit to Australian industry and research.Read moreRead less
Nanosized peptide nucleic acid - metal complex hybrids as catalysts for the cleavage of phosphate ester bonds in biological molecules. The information from Human Genome Project is being used to generate molecules with a variety of therapeutic and diagnostic applications. The capability to design, synthesise and manipulate functional molecules that mimic biological processes will underpin many emerging applications. In this project, macrocyclic metal complexes that catalyse the cleavage of phosph ....Nanosized peptide nucleic acid - metal complex hybrids as catalysts for the cleavage of phosphate ester bonds in biological molecules. The information from Human Genome Project is being used to generate molecules with a variety of therapeutic and diagnostic applications. The capability to design, synthesise and manipulate functional molecules that mimic biological processes will underpin many emerging applications. In this project, macrocyclic metal complexes that catalyse the cleavage of phosphate ester bonds in biological molecules will be developed. Active complexes will be incorporated into nanosized peptide nucleic acid (PNA) - metal complex hybrids and applied as artificial enzymes in the sequence specific cleavage of RNA and DNA. Novel applications of these ?artificial enzymes? in biotechnology are anticipated.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561013
Funder
Australian Research Council
Funding Amount
$220,000.00
Summary
X-ray diffraction System for Protein Crystallography and Structural Biology. Knowledge of protein structures enables researchers to explain cellular function at a molecular level. In particular, it provides essential information to understand the mechanism of diseases, such as cancer or AIDS, and it ultimately leads to the design of better drugs.
An in-house X-ray protein crystallography facility will allow us to determine the structures of key proteins effectively and competitively, opening up ....X-ray diffraction System for Protein Crystallography and Structural Biology. Knowledge of protein structures enables researchers to explain cellular function at a molecular level. In particular, it provides essential information to understand the mechanism of diseases, such as cancer or AIDS, and it ultimately leads to the design of better drugs.
An in-house X-ray protein crystallography facility will allow us to determine the structures of key proteins effectively and competitively, opening up extensive possibilities for multi-disciplinary ground-breaking research.
The University research portfolio has evolved to embrace the revolution in structural biology with numerous projects and collaborations focusing on proteins involved in bacterial infections, degenerative disorders and biotechnological applications.Read moreRead less
Gating, specificity and regulation of the YggB channel protein from Corynebacterium glutamicum. The proposed research will greatly contribute to our understanding of the functioning of a bacterial membrane channel/transporter, which has played a significant role in biotechnology of commercially important amino acids. A direct national benefit will result from establishing collaboration with a leading German laboratory providing expertise in protein biochemistry and molecular microbiology not ava ....Gating, specificity and regulation of the YggB channel protein from Corynebacterium glutamicum. The proposed research will greatly contribute to our understanding of the functioning of a bacterial membrane channel/transporter, which has played a significant role in biotechnology of commercially important amino acids. A direct national benefit will result from establishing collaboration with a leading German laboratory providing expertise in protein biochemistry and molecular microbiology not available in Australia. The acquired knowledge will present an original contribution which will have a strong impact on a very competitive field of molecular microbiology and biotechnology.Read moreRead less
Negative ion mass spectrometry: fundamental studies and applied applications. We seek to:
(i) establish negative ion mass spectrometry as an analytical tool for the sequencing of proteins and to probe the structures of active peptide Ca2+ calmodulin complexes which, for example, inhibit the formation of NO from nitric oxide synthases. Controlling the concentration of nitric oxide may assist with the treatment of inflammatory and cardiac diseases, stroke and diseases of the central nervous syst ....Negative ion mass spectrometry: fundamental studies and applied applications. We seek to:
(i) establish negative ion mass spectrometry as an analytical tool for the sequencing of proteins and to probe the structures of active peptide Ca2+ calmodulin complexes which, for example, inhibit the formation of NO from nitric oxide synthases. Controlling the concentration of nitric oxide may assist with the treatment of inflammatory and cardiac diseases, stroke and diseases of the central nervous system.
(ii) to study the possibility of the formation of biological molecules of life in interstellar regions
(iii) to train graduate students to international standards in the chemistry of proteomics.Read moreRead less
Stuctural analysis of RNA polymerase elongation complexes. RNA polymerase (RNAP) is an essential enzyme in all living cells. Its role is to convert the genetic information stored in genes into a message that can be converted into protein. Many additional factors are required to ensure that this enzyme functions correctly in the cell. The aim of this project is to obtain structural information on a bacterial RNAP complexed with an essential transcription factor called NusA. Using this information ....Stuctural analysis of RNA polymerase elongation complexes. RNA polymerase (RNAP) is an essential enzyme in all living cells. Its role is to convert the genetic information stored in genes into a message that can be converted into protein. Many additional factors are required to ensure that this enzyme functions correctly in the cell. The aim of this project is to obtain structural information on a bacterial RNAP complexed with an essential transcription factor called NusA. Using this information, plus data already obtained on the structure of this enzyme complexed with another essential factor called sigma, we will design small molecules to inhibit the interaction of these essential factors with polymerase. These molecules will serve as leads for the development of new antibiotics.Read moreRead less
Plasmid maintenance and interactions with the host cell and its genome. Plasmids are extrachromosomal genetic elements that play a central role in the evolution of bacteria. They are the most dynamic component of the bacterial genome, augmenting the host chromosome by conferring a range of significant phenotypes that facilitate environmental adaptation. This project aims to elucidate fundamental aspects of the relationship between plasmids and their bacterial hosts. Significant outcomes include ....Plasmid maintenance and interactions with the host cell and its genome. Plasmids are extrachromosomal genetic elements that play a central role in the evolution of bacteria. They are the most dynamic component of the bacterial genome, augmenting the host chromosome by conferring a range of significant phenotypes that facilitate environmental adaptation. This project aims to elucidate fundamental aspects of the relationship between plasmids and their bacterial hosts. Significant outcomes include understanding the molecular basis of efficient plasmid inheritance in bacterial populations, and exploration of the innovative hypothesis that plasmids modulate expression of the host chromosome, a possibility that would profoundly alter our view of how plasmids influence host phenotype.Read moreRead less
DNA Dynamics is Shear and Extensional Flows: Simulation and Single Molecule Experiments. The proposal seeks to establish a collaboration between Monash University and Stanford University in order to combine several recent experimental and theoretical advances that have been made by the individual groups in single molecule experimental techniques, extensional rheometry, and molecular rheology, to obtain new insights into the structure and dynamics of biopolymers. The central aim is to make a sign ....DNA Dynamics is Shear and Extensional Flows: Simulation and Single Molecule Experiments. The proposal seeks to establish a collaboration between Monash University and Stanford University in order to combine several recent experimental and theoretical advances that have been made by the individual groups in single molecule experimental techniques, extensional rheometry, and molecular rheology, to obtain new insights into the structure and dynamics of biopolymers. The central aim is to make a significant contribution towards bringing state-of-the-art techniques used for the characterization of polymeric systems to bear on the nature and origin of the elastic properties of biopolymers.Read moreRead less