Structural Characterisation Of A Natural Inhibitor Of Sporulation Bound To Its Histidine Kinase Target
Funder
National Health and Medical Research Council
Funding Amount
$261,000.00
Summary
Many bacteria, including some which are virulent pathogens such as anthrax (Bacillus anthracis), are able to enter a dormant state by forming spores (sporulation). These spores are extremely robust and may persist in the environment buried in the soil for example for hundreds of years. The initiation of sporulation occurs in response to changes in the cellular and environmental conditions which threaten the free replicating existence of the bacterium. The process of sporulation is controlled at ....Many bacteria, including some which are virulent pathogens such as anthrax (Bacillus anthracis), are able to enter a dormant state by forming spores (sporulation). These spores are extremely robust and may persist in the environment buried in the soil for example for hundreds of years. The initiation of sporulation occurs in response to changes in the cellular and environmental conditions which threaten the free replicating existence of the bacterium. The process of sporulation is controlled at the molecular level by a complex signaling relay. It is of course vital for the existence of the organism that control of sporulation is tightly regulated - preventing the onset of spore-formation in any but the desired circumstances. We aim to determine the three-dimensional structures of the molecules involved in this regulated process and how, by interacting with each other, they can pass on the signal to the bacterium to either start or stop the spore forming process. Ultimately, the results of this work might lead to antibacterial agents which could be used to control particularly dangerous strains of bacteria.Read moreRead less
Tyrosine Kinases And Phosphatases In Cell Cycle Checkpoint Responses
Funder
National Health and Medical Research Council
Funding Amount
$513,946.00
Summary
In order for an organism to grow and develop, the cells that make up the tissues and organs need to undergo a process of cellular division, wherein individual cells grow and then divide into two cells. During this process of cellular growth and division the entire genome needs to be duplicated (this occurs during S-phase) and then divided equally into the two daughter cells. In S-phase several so-called 'checkpoint' mechanisms exist which ensure that this occurs in an orderly and precise manner. ....In order for an organism to grow and develop, the cells that make up the tissues and organs need to undergo a process of cellular division, wherein individual cells grow and then divide into two cells. During this process of cellular growth and division the entire genome needs to be duplicated (this occurs during S-phase) and then divided equally into the two daughter cells. In S-phase several so-called 'checkpoint' mechanisms exist which ensure that this occurs in an orderly and precise manner. The so-called 'DNA replication checkpoint' delays S-phase progression in response to 'replication stresses' that may otherwise cause DNA damage. Protein tyrosine kinases (PTKs) are hyperactivated in many human solid tumours and blood malignancies contributing to varied aspects of tumour progression. Our preliminary studies indicate that the inactivation of PTKs by protein tyrosine phosphatases may be essential for the suppression of S-phase progression in response to replication stress. Our goal is to understand the molecular mechanisms by which PTKs and tyrosine phosphatases contribute to S-phase checkpoints. Our studies will provide important insights into DNA replication stress-induced checkpoint responses in mammals and identify unprecedented mechanisms by which hyperactivated PTKs may contribute to tumour development.Read moreRead less