Research
Research
Research
Every cell must divide in order to grow and propagate and one of the fundamental questions in biology is to understand how cells determine when and where to divide. Most of our knowledge about bacterial cell division comes from studying a handful of unicellular model organisms. However, much less is known about how filamentous bacteria, like Streptomyces, grow and divide.
Streptomyces are Gram-positive, antibiotic-producing soil bacteria with a complex, multicellular life cycle involving two distinct modes of cell division: vegetative cross-wall formation and sporulation septation. Both these forms of cell division require the bacterial tubulin homolog FtsZ, which polymerises into a ring-like structure (Z-ring) and eventually leads to the synthesis of a division septum.
To study the cell biological processes that control the two functional and architectural different kinds of cell division in Streptomyces at the single-cell level, we use Streptomyces venezuelae as our model system for developmental studies of filamentous growing bacteria.
Streptomyces life-cycle
Time-lapse movie showing FtsZ ring formation
Current research projects in the lab:
1. Determining the mechanism for division-site placement during sporulation-specific cell division
During sporulation, Streptomyces have to simultaneously position dozens of evenly spaced Z-rings in a ladder-like pattern between the segregating chromosomes along the length of sporogenic hyphae. These Z-rings go on to constrict and eventually lead to the release of chains of unigenomic spores.
Importantly, Streptomyces lack homologs of the canonical negative control systems that ensure proper Z-ring placement in many unicellular bacteria and there is no geometrical reference point for midcell. How the highly coordinated polymersiation of FtsZ into ladders of Z-rings is achieved at the molecular and cellular level is still poorly understood.
This project aims to determine the molecular mechanism that controls Z-ring placement during sporulation-specific cell division.
Sporulation-specific cell division: Time-lapse series showing the formation of dozens of equally-spaced Z-rings which result in the septation of the hyphal filament into chain of unigenomic spores.
2. Understanding the importance of cellular compartmentalisation for multicellular development
During vegetative growth, Z-ring formation leads to the formation of so-called vegetative cross-walls (CWs), which are division septa that divide the growing hyphae occasionally into long multigenomic compartments that remain physically connected. Although the existence of CWs is well documented in the literature, their exact nature and physiological significance are still unknown.
In this project, we aim to unravel the molecular basis for CW formation and determine the importance of these FtsZ-dependent division septa for multicellular growth and development of Streptomyces.
Cell division during vegetative growth: Cross-walls (CW) divide the growing hyphae into long multigenomic compartments.
To ensure regular septum formation and efficient cell–cell separation, the Z-ring interacts with a number of essential and accessory proteins. While some of these proteins seem to be conserved across different species, many are not.
We recently reported that two dynamin-like proteins play a critical role in Z-ring stabilsation. However, how the dynamins directly mediate the effect on cell division is still largely unclear.
The aim of this project is to dissect the function of the dynamins during sporulation-specific cell division and to identify additional divisome components that play a crucial role for Z-ring formation and function.
Kymographs of Z-ring stability during sporulation-specific cell division in the wildtype and in the dynamin mutant, in which many Z-rings disassembly prematurely leading to a sporulation septation defect.
3. Identifying novel cell division proteins important for the formation, stabilisation and function of Z-rings