Mechanisms for establishment and regulation of polar growth in Streptomyces venezuelae and other Actinobacteria

My PhD project is about investigating the mechanisms of the regulation of polar growth in Streptomyces venezuelae and other Actinobacteria. The mechanisms that control growth, cell wall synthesis, and cell shape in bacteria are of large fundamental importance. The peptidoglycan cell wall is crucial for the maintenance of integrity and shape of bacteria. Synthesis of the cell wall must occur at the right time and place in the cell. Cytoskeleton-like proteins in the cytoplasm play key roles in the spatial and temporal control of peptidoglycan assembly by scaffolding and organizing protein complexes. These proteins and the processes related to peptidoglycan synthesis are also promising targets for antibiotics. The tubulin-homologue FtsZ directs bacterial cell division, while the actin-homologue MreB directs cell wall elongation in most rod-shaped bacteria. However, large, and important groups of bacteria, sch as Actinobacteria, grow in an MreB-independent manner. Actinobacteria is a large group of Gram-positive bacteria which comprise severe pathogens such as mycobacteria which cause diseases like tuberculosis, as well as industrially important antibiotic-producer bacterial species such as Streptomycetes, which produce the majority of our clinically used antibiotics. The Actinobacteria grow by building the cell wall in restricted zones at the cell poles, and this is referred to as polar growth or apical growth.This mode of growth does not involve MreB. Instead, a third type of cytoskeleton-like structure, a protein assembly formed by the coiled-coil protein DivIVA, directs peptidoglycan assembly to occur in restricted zones at the cell poles. We refer to the multi-protein complex formed around DivIVA as the polarisome. However, the system for orchestration of polar growth remains poorly understood, despite the fact that it is essential for growth and viability of Actinobacteria. My PhD project will investigate molecular mechanisms involved in controlling peptidoglycan synthesis, cell growth, and cell morphology determination in Actinobacteria, using Streptomyces venezuelae as the main model organism. The main focus will be on mechanisms controlling the DivIVA-based polar growth and cell polarity.