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When Immune Systems Join Forces: Structural Basis of Cooperative Prokaryotic Immunity
Doctoral study program
Life Sciences (Faculty of Science, Masaryk University)
Supervisor
Annotation
Every organism faces a constant battle against invading genetic elements such as viruses and plasmids. To survive, bacteria and archaea have evolved a remarkable diversity of immune systems that detect and eliminate foreign DNA. Traditionally, these systems have been studied as independent defense mechanisms. However, recent discoveries suggest that some immune systems cooperate, forming more complex defense networks capable of responding to a broader range of threats.
One particularly intriguing example is provided by prokaryotic Argonaute proteins (pAgos), programmable nucleic-acid recognition factors found throughout bacteria and archaea. While some pAgos directly destroy invading DNA, many are genetically associated with proteins belonging to entirely different immune pathways. Why these systems became linked during evolution and how they cooperate at the molecular level remains unknown.
This PhD project will investigate how Argonaute proteins interact with partner immune systems to create novel defense strategies. Using state-of-the-art electron cryomicroscopy (cryo-EM), the student will determine structures of immune complexes captured at different stages of substrate recognition, remodeling, and processing. These structural studies will be complemented by biochemical, biophysical, microbiological, and evolutionary analyses performed in collaboration with leading international laboratories.
A particular focus will be understanding how catalytically inactive Argonautes have evolved into programmable regulators of partner immune proteins and how such cooperation increases the complexity and robustness of microbial immunity. By visualizing molecular machines in action and uncovering their dynamic mechanisms, the student will reveal fundamental principles governing the evolution and organization of immune systems.
The project sits at the interface of structural biology, microbiology, evolutionary biology, and biophysics, providing training in cryo-EM, protein biochemistry, computational structural biology, and molecular mechanism discovery.
Join us to uncover how evolution creates new immune systems by combining existing ones into more powerful defense machines.
Recommended literature
- Koopal B. et al. Diverse prokaryotic Argonaute-associated immune systems. Science (2023).
- Ugarte R. et al. Molecular mechanisms of Argonaute-associated defense systems. Mol Cell (2025).
- Makarova KS et al. Evolutionary classification of CRISPR-Cas systems. Nat Rev Microbiol (2020).
- Swarts DC et al. Prokaryotic Argonautes: mechanisms and biological roles. Nat Rev Microbiol.
- Finocchio G. et al. Cooperation between prokaryotic immune systems.
Research area
Microbial immunity and nucleic-acid biology
Keywords
Prokaryotic immunity; Argonaute proteins; CRISPR-Cas; Cryo-electron microscopy (cryo-EM); Structural biology; Molecular evolution; Host–virus interactions; Cooperative immune systems; Protein–DNA interactions
Funding of the PhD candidate
GACR, OP JAK
Requirements for candidate
Applicants should have a strong background in one or more of the following areas or related fields: structural biology, molecular biology, biochemistry or biophysics. Experience with Linux-based systems and scripting would be advantageous, but is not essential.
We are equally interested in candidates who are enthusiastic about science, motivated by the project topic, keen to learn new experimental and computational methods, and driven to tackle important and challenging scientific questions. Hard skills are valuable, but curiosity, commitment and scientific ambition will be valued just as highly.
Information about the supervisor
Prof. Richard Stefl is a leading structural biologist whose lab combines cryo-EM, NMR, and integrative structural biology to uncover how RNA–protein complexes control gene expression and cellular regulation. As an ERC grant holder and head of the CEITEC Centre for Structural Biology, he offers PhD students access to cutting-edge technologies, interdisciplinary mentoring, and an inspiring environment at the forefront of RNA biology and molecular mechanisms of gene silencing.
Overall Summary Output
Total publications: 49
Total citations: 2400+
H-index: 28
Journal Highlights: Cell, Molecular Cell, Genes & Dev, EMBO J, PNAS, NSMB, Nature Comms
Supervision since PI (total): 8 postdocs, 1 technician, 13 PhD students, 11 undergraduate students