Active Cells, Biochemistry & Physiology Genetics & Molecular Biology

Mechanisms of FtsZ-based cell division

In plain English

AI plain-English summary

Bacteria and archaea build a molecular ring called the Z-ring to pinch themselves in two during division, and this project aims to show exactly how that ring works at the atomic level. Cell division is fundamental to all life, yet the machinery that drives it in bacteria and archaea remains poorly understood. Most antibiotics target cell wall synthesis, but rising resistance means we need new ways to disrupt bacterial growth. Without a clear picture of how the division machinery assembles and activates, designing drugs that block it is guesswork. The team will use electron cryotomography to image complete division planes inside cells, revealing the Z-ring’s structure. They will also analyse the divisome—the protein complex that builds new cell wall—to understand how it polymerises lipid II into peptidoglycan, and test whether they can recreate division from scratch in artificial liposomes. Because some wall-less archaea and bacteria still divide, the work will also uncover alternative mechanisms. If successful, this fundamental science could reveal new targets for antibiotics that block division without triggering existing resistance pathways. It may also enable synthetic biologists to build self-dividing artificial cells, with potential applications in drug delivery or biosensing. The research is curiosity-driven, but past work on bacterial cell division has already led to the development of drugs like the carbapenems.

View original technical description
Most bacteria and archaea divide using a cytokinetic structure, the Z-ring, which contains the tubulin-like FtsZ protein. The Z-ring recruits the divisome, a trans-membrane protein complex that synthesises peptidoglycan, which leads to cell constriction and division through inwards growth of the cell wall. With this proposal we aim to unravel the molecular events that drive cell division. To understand how the Z-ring organises division, we will reveal its structure using electron cryotomography in cells, for which we have developed EM technology to image complete division planes. We will uncover how cell wall is grown for division through a comprehensive structure and function analysis of divisomes, including how they polymerise lipid II into peptidoglycan. How Z-ring attachment activates the divisome will be analysed in vitro and in vivo. Usefulness and completeness of the mechanisms revealed will be tested with in vitro liposome experiments recapitulating peptidoglycan polymerisation and Z-rings, and enabling cell division reconstitution, a goal of synthetic biology. Since some FtsZ-containing archaea and bacteria have no cell wall, we will investigate how they divide without it. Finally, since cell elongation by the elongasome also involves peptidoglycan synthesis, we will uncover why the divisome thickens cell wall, while the elongasome widens it.

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Researchers

Jan Löwe (EPMC Awardee)

Related Research

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Original classification

Discovery Award

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