Bacterial Proteomics: From Cell Division to Novel Antibiotic Targets. When a cell divides it is essential that each newborn cell gets a complete copy of the DNA. To ensure that this happens, cell division must be tightly controlled. It is not known how this occurs in bacteria. However, if we knew what molecules were involved in this control, we could target them to kill harmful bacteria. This project aims to identify such regulatory molecules as candidate targets for antimicrobial agents, with a ....Bacterial Proteomics: From Cell Division to Novel Antibiotic Targets. When a cell divides it is essential that each newborn cell gets a complete copy of the DNA. To ensure that this happens, cell division must be tightly controlled. It is not known how this occurs in bacteria. However, if we knew what molecules were involved in this control, we could target them to kill harmful bacteria. This project aims to identify such regulatory molecules as candidate targets for antimicrobial agents, with a view to developing powerful, novel antibiotics to protect us from the imminent threat of bioterrorism and antibiotic-resistant bacteria.
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The Fine Tuned Physiology of Microaerophilic Gastric Spirilla. The aim of the project is to understand the molecular basis of fundamental properties of the physiology of enterogastric spiral bacteria of the genera Campylobacter and Helicobacter. The characteristics of these obligate microaerophiles which will be investigated are their aerobic respiratory chains, the special metabolites and enzymes involved in thiol-disulphide redox balance, and their essential requirement for carbon dioxide. Mic ....The Fine Tuned Physiology of Microaerophilic Gastric Spirilla. The aim of the project is to understand the molecular basis of fundamental properties of the physiology of enterogastric spiral bacteria of the genera Campylobacter and Helicobacter. The characteristics of these obligate microaerophiles which will be investigated are their aerobic respiratory chains, the special metabolites and enzymes involved in thiol-disulphide redox balance, and their essential requirement for carbon dioxide. Microaerobes include some bacteria, archea and protozoa. Realisation of the widespread habitats and importance of microaerophiles, has led recently to a vigorous interest in understanding their physiology. Knowledge of the basic properties of microaerophily has potential applications to Environmental Microbiology, Agriculture, Industrial Microbiology, Veterinary Science and Medicine.Read moreRead less
Bacterial polycyclic aromatic hydrocarbon transport and degradation. This project aims to investigate the molecular processes underpinning the degradation of polycyclic aromatic hydrocarbons (PAHs) by bacteria. PAHs are persistent environmental contaminants linked to several human diseases, including cancer. Bacteria capable of degrading PAHs could be used to naturally and effectively reduce environmental PAH loads to below safe levels. The project will apply techniques in functional genomics an ....Bacterial polycyclic aromatic hydrocarbon transport and degradation. This project aims to investigate the molecular processes underpinning the degradation of polycyclic aromatic hydrocarbons (PAHs) by bacteria. PAHs are persistent environmental contaminants linked to several human diseases, including cancer. Bacteria capable of degrading PAHs could be used to naturally and effectively reduce environmental PAH loads to below safe levels. The project will apply techniques in functional genomics and biochemistry to help define the ways that PAHs are taken up from the environment by bacteria, their fate within bacterial cells, and the ways that bacteria overcome the inherent toxicity of PAHs. The knowledge generated is expected to enhance our capacity to rationally deploy bacteria for PAH degradation.Read moreRead less
A functional genomic approach for understanding metal ion adaptation in marine cyanobacteria. Unicellular marine cyanobacteria constitute 20-40% of total marine chlorophyll biomass and carbon fixation, and hence significantly impact the global carbon cycle and are very relevant to combating global warming. This research will reveal some of the major mechanisms by which marine cyanobacteria have adapted to metal levels in coastal and oligotrophic environments. Thus these results will help us und ....A functional genomic approach for understanding metal ion adaptation in marine cyanobacteria. Unicellular marine cyanobacteria constitute 20-40% of total marine chlorophyll biomass and carbon fixation, and hence significantly impact the global carbon cycle and are very relevant to combating global warming. This research will reveal some of the major mechanisms by which marine cyanobacteria have adapted to metal levels in coastal and oligotrophic environments. Thus these results will help us understand the distribution and diversity of these organisms in relation to global primary productivity. They will also lead to the development of more robust biomarkers for metal stress and pollution in coastal environments.Read moreRead less
Evolutionary and ecological complexity in an experimentally controlled environment. Understanding the capacity and mechanism of microbial evolution provides the framework for developing new strategies for preventing infectious disease. If we know how evolution works, it will be possible to hamper the capacity to evolve as a mechanism of preventing new diseases and controlling existing ones. This project will provide a mechanistic description of evolution in real time under controlled conditions. ....Evolutionary and ecological complexity in an experimentally controlled environment. Understanding the capacity and mechanism of microbial evolution provides the framework for developing new strategies for preventing infectious disease. If we know how evolution works, it will be possible to hamper the capacity to evolve as a mechanism of preventing new diseases and controlling existing ones. This project will provide a mechanistic description of evolution in real time under controlled conditions. This detailed information will be used in the education of the public and in debates about evolution. The project will also train at least five students in molecular and evolutionary microbiology, essential for facing future challenges.
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Novel peptide mimics for the disruption of chemical communication in bacteria. It is now well established that bacteria communicate with each other via small diffusible signalling molecules and coordinate their activities such as biofilm formation, swarming and expression of virulence factors in a coordinated manner. This project will investigate the synthesis of novel organic molecules that have the capacity to disrupt chemical communication in bacteria. This could allow control of the unwante ....Novel peptide mimics for the disruption of chemical communication in bacteria. It is now well established that bacteria communicate with each other via small diffusible signalling molecules and coordinate their activities such as biofilm formation, swarming and expression of virulence factors in a coordinated manner. This project will investigate the synthesis of novel organic molecules that have the capacity to disrupt chemical communication in bacteria. This could allow control of the unwanted microbial activity without the use of growth inhibitory agents such as antibiotics, preservatives and disinfectants that select for the resistant organisms. This elegant approach to eradicating the virulence behaviour of microbes represents a novel strategy to combat antimicrobial resistance.Read moreRead less
Bacterial Cell Division: Discovering how it begins and the network of protein interactions it requires. All cells must coordinate cell division with chromosome replication to ensure that the DNA is partitioned equally into newborn cells. We will establish the defect of a novel mutant blocked in the earliest stage of cell division in bacteria to obtain unique information about this vital regulatory step. We will use our newly discovered protein interaction network to establish what role protein i ....Bacterial Cell Division: Discovering how it begins and the network of protein interactions it requires. All cells must coordinate cell division with chromosome replication to ensure that the DNA is partitioned equally into newborn cells. We will establish the defect of a novel mutant blocked in the earliest stage of cell division in bacteria to obtain unique information about this vital regulatory step. We will use our newly discovered protein interaction network to establish what role protein interactions play in integrating cell division with other biological pathways in the cell to ensure its tight regulation. Our discoveries will facilitate the design of new antibiotics that target cell division to fight antibiotic-resistant bacteria and bioterrorism organisms.Read moreRead less
Structures to Solve Conflicts of DNA Replication and RNA Transcription. This project aims to understand how new DNA is made so quickly and without mistakes in cells that are about to divide, in spite of competition from other processes happening at the same time on the DNA that should stop or interfere with it, such as the synthesis of RNA. The project expects to use the latest available methods to uncover what the microscopic natural machines that make DNA and RNA look like, and how they compet ....Structures to Solve Conflicts of DNA Replication and RNA Transcription. This project aims to understand how new DNA is made so quickly and without mistakes in cells that are about to divide, in spite of competition from other processes happening at the same time on the DNA that should stop or interfere with it, such as the synthesis of RNA. The project expects to use the latest available methods to uncover what the microscopic natural machines that make DNA and RNA look like, and how they compete with each other for access to DNA. Potential outcomes include the identification of processes that can be compromised by small molecules that may be developed into new antibiotics. This would be of great benefit - new antibiotics are urgently needed as one approach to countering the threat of antimicrobial resistance.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
Structural analysis and functional inactivation of bacterial transcription complexes. RNA polymerase 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. As such, the bacterial RNA polymerase represents an ideal target for the development of new antibiotics which will be important in maintaining the health of the Australian community and also in protecting the community from the very real thr ....Structural analysis and functional inactivation of bacterial transcription complexes. RNA polymerase 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. As such, the bacterial RNA polymerase represents an ideal target for the development of new antibiotics which will be important in maintaining the health of the Australian community and also in protecting the community from the very real threat of bioterrorism organisms such as anthrax. This project is designed to identify molecules for development as new antibiotics that are effective against RNA polymerase.Read moreRead less