Nature and regulation of the essential cell polarity organelle in Actinobacteria

Growth of the Gram-positive Actinobacteria depends critically on targeting of cell envelope biogenesis to cell poles, where cell wall assembly occurs.

Our aim is to elucidate broadly significant mechanisms for establishment of this cell and growth polarity: (i) Based on previous observations and new data, we propose that proteins that orchestrate polar growth in Streptomyces bacteria form, based on liquid-liquid phase separation, a membrane-less organelle that interacts with the cytoplasmic membrane.

We will experimentally test this model and determine what features of the scaffolding proteins are critical for formation and properties of the organelle, and how they affect cell wall synthesis and cell shape.

Client proteins that are recruited to the organelle will be identified and their functions in polar growth determined. (ii) We have identified regulatory genes that profoundly affect cell shape and mycelial morphology.

The encoded regulators (Ser/Thr protein kinase; Ras-like GTPases coupled to transmembrane receptors; histidine pseudokinase) act on the polarity organelle.

We aim to uncover molecular mechanisms by which the fundamental mode of growth is regulated to achieve the morphological plasticity associated with the multicellular life style of streptomycetes.

These studies will yield novel and original insights into the nature of the polarity organelle, the core of which is essential and constitute an antibiotic target in pathogens like Mycobacterium tuberculosis.