Understanding cell division control and dynamics in Streptomyces and Mycobacteria

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Every cell must divide in order to grow and to propagate. In most bacteria, the splitting of the cell is accomplished by a large, multi-component division machine. At the heart of this machine is a protein called FtsZ, which assembles into a scaffold that is essential for the recruitment of additional cell division proteins. One of the key questions in fundamental research is to understand how cells control the correct timing for the assembly and the architecture of the FtsZ-scaffold. In addition, studying the process of cell division is of great interest because it can help with the design of new antibiotics that specifically target components of the cell division complex in health-threatening bacteria.We have recently identified a novel component of the cell division machinery that regulates the dynamics of the FtsZ-scaffold assembly in the harmless antibiotic producing bacteria Streptomyces. Importantly, this new scaffold regulator is also present in many serious pathogens like M. tuberculosis or C. diphtheriae. Consequently, gaining a fundamental understanding of the mechanism of cell division in Streptomyces will help us learn more about how their disease-causing relatives divide and may offer the opportunity to develop innovative strategies to inhibit cell division in these microbial pathogens.Since it is completely unknown how this new regulator controls cell division in bacteria, we aim to a) Characterise the function of the regulator in Streptomyces and Mycobacteriab) Determine how the regulator influences the dynamics of FtsZ scaffold assembly in vitroc) Understand the structural basis for the interaction of the regulator with FtsZTo achieve these aims, we will employ a range of molecular, cell biological and biochemical techniques and complement our functional characterisation studies with the structural elucidation of the regulator on its own and in complex with FtsZ.