Single-cell dynamics of bacterial immunity

Bacteria encode a diverse arsenal of anti-phage defence systems. Combining microfluidics, quantitative live-cell imaging and bacterial genetics, we resolve how these systems sense infection, how they are coordinated in time and space within single cells, and how they act together to protect the population.

Zorya at work: phage infection deforms the cell envelope, so the ZorB2 domains can reach the peptidoglycan (how exactly the gap closes is not yet known). Protons then flow through the bound ZorB and drive the rotation of ZorA, whose tail reels in the phage DNA and ZorC and ZorD destroy it. Model based on Hu, Popp et al. 2025, Nature; DNA winding by the tail is a proposed mechanism.

Research

Bacteria are under constant attack by phages and defend themselves with a remarkable diversity of immune systems. Most species carry several of them, often clustered in defence islands. How these modules are coordinated in time and space, and how they are embedded in the wider physiology of the cell, remains largely unknown.

Defence in concert

Defence systems differ in how they sense infection, where they localise in the cell and when they act, and some confer protection only in combination. The figure maps the systems we study within a single cell, together with current mechanistic knowledge and the open questions we address.

Goodsell-style illustration of an Escherichia coli cell under phage attack: Zorya I and Zorya II in the inner membrane, Druantia and RecBCD on incoming phage DNA, Lamassu at a phage DNA end, and the defence island on the chromosome. 123456

Structures: ZorA5B2 8QYD and 8VVI, ZorC 8R68, ZorD 8QY7, ZorE AlphaFold P0DW03, DruE 9TU7, DruH 9TUD, RecBCD 1W36, LmuACB 9HQU. Phages, DNA, membranes and cytoplasm are schematic.

1Zorya I

A proton-driven ZorA5B2 motor; its tail recruits ZorC and ZorD to destroy phage DNA.

How does ZorAB sense the phage at the cell envelope?

2Zorya II

The same 5:2 motor core, paired with the nickase ZorE.

How is ZorE brought to the phage DNA?

3Druantia III

DruE recognises single-stranded phage DNA and unwinds it directionally.

Why is it so much stronger together with Zorya II?

4RecBCD

The cell's own DNA-end processing machine.

A shared hub that connects defence systems?

5Lamassu

Senses phage DNA ends and releases the nuclease LmuA: abortive infection.

When does the cell sacrifice itself instead of defending?

6Defence island

Several systems encoded side by side on the chromosome.

How are they coordinated in time and space in single cells?

How we investigate it

We follow defence in single living cells and connect what we see to the structures of the defence complexes.

  1. 1

    Engineer

    Reporter fusion in time-lapse microscopy over two hours.

    We combine or remove defence systems in E. coli, build fluorescent reporters and label phages to follow infection dynamics.

  2. 2

    Watch

    Animation: labelled phages reach cells in a mother machine (with Dietrich Kohlheyer, FZ Jülich). Right: real channels with labelled phages.

    Microfluidic mother machines keep thousands of single cells under constant conditions while phages arrive. Live-cell and TIRF microscopy show where and when each defence system acts.

  3. 3

    Resolve

    ZorA5B2 (PDB 8QYD) between the inner membrane and the peptidoglycan.

    We aim to unravel the mechanistic details of anti-phage defence systems: with structural biologists we determine the architecture of defence complexes and test proposed mechanisms in living cells.

  4. 4

    Quantify

    BactoMate: segmentation, foci, cell outlines and tracking.

    BactoMate, our open-source platform, turns microscopy into single-cell data: segmentation, foci, tracking and lineages, in one workflow.

People

Portrait of Dr. Philipp Popp

Dr. Philipp Popp

Einstein Independent Researcher and head of the Molecular Infection Microbiology group at the Institute of Biology, Humboldt-Universität zu Berlin. The group studies how anti-phage defence systems act together in single bacterial cells.

PhD students

Portrait of Lasse Hallenga

Lasse Hallenga

PhD student, since 2025

Development of image analysis tools

Portrait of Adhvaidhi Kuntran

Adhvaidhi Kuntran

PhD student, since 2025

Sensing of phage infection by Zorya

Portrait of Nikos Moustakas

Nikos Moustakas

PhD student, since 2026

Coordinated immunity in a single cell

Students

Valentin Schmitt

B. Sc. student, since 2026

Mechanism of Druantia immunity

Join us

PhD students and postdocs

We welcome PhD students and postdocs who want to apply for their own funding to work with us. We support fellowship applications, for example to the Alexander von Humboldt Foundation, Marie Skłodowska-Curie Actions, EMBO, DAAD or the Boehringer Ingelheim Fonds.

B. Sc. and M. Sc. theses

We offer thesis projects in microbiology and microscopy data analysis. Send us a short statement of interest and your CV, together with a short project idea or the methods you would most like to work with.

Alumni
  • Sarah FornoffB. Sc. thesis and student assistant2024–2026
  • Aioeux MedlowM. Sc. intern2026
  • Selina SchwarzM. Sc. intern2026
  • Merle GradtM. Sc. intern2026

Funding

Current funding

  • SPP 2330
  • Berlin University Alliance
  • Einstein Foundation Berlin