Anat Herskovits Lab

Anat Herskovits Lab

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Bacteria-Virus Cooperation: Redefining Host-Pathogen Interactions

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Research Overview

Our laboratory investigates a fundamental question in microbiology: How do bacteria and their integrated viruses (prophages) interact to influence bacterial infection? Our work has revealed unexpected cooperative relationships that challenge traditional views of bacteria-virus interactions and open new avenues of research and directions for therapeutic intervention.

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Our model organism- Listeria monocytogenes

Listeria monocytogenes is an intracellular pathogen, the causative agent of Listeriosis disease. This bacterium can transition from living in soil to invading human cells, essentially transforming from an environmental microbe into a sophisticated pathogen. What makes it particularly fascinating is its ability to hijack host cell machineries, such as the actin polymerization machinery, which allows it to propel itself through cells using actin "rockets" and spread directly from cell to cell, effectively hiding from the immune system.

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In our lab, we've discovered something extraordinary: Listeria has evolved cooperative relationships with its integrated viruses (prophages), using them as precise genetic switches to control its infection process. This finding opens up a whole new understanding of how bacteria and viruses can work together rather than just having a predator-prey relationship.

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Listeria is an excellent experimental model- it's easy to grow in the lab, genetically tractable, and its infection process can be studied in detail. We use Listeria to study pathogen-phage interactions upon infection of mammalian cells and their adaptation to the mammalian environment. It's like having a window into the complex world of bacteria-phage adaptation and evolution.

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Key Discoveries

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1. Active Lysogeny: A New Paradigm

We discovered that prophages can function as sophisticated genetic switches rather than just being passive DNA elements or destructive agents. This phenomenon, which we termed "active lysogeny," represents a fundamental shift in our understanding of bacteria-virus relationships. In Listeria monocytogenes, a prophage precisely excises from and reintegrates into a bacterial gene (comK) to control bacterial infection processes without triggering viral reproduction.

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2. Coordination of Viral Elements

We uncovered a remarkable system where multiple viral elements within bacteria coordinate their activities through a shared regulatory system – e.g., the MpaR metalloprotease. This master regulator orchestrates the behaviour of different viral elements to enhance bacterial survival and infection capability, demonstrating a new level of bacteria-virus cooperation.

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3. Evolutionary Adaptation of Viruses to Their Host

Our research revealed how viral elements have evolved to enhance bacterial infection rather than prioritizing their own reproduction – an intriguing example of evolution driving cooperation rather than conflict. This adaptation suggests long-term co-evolution between bacteria and viruses in the context of host infection.

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Current Research Directions

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• Investigating the molecular mechanisms controlling phage responses in the mammalian environment

• Identifying new bacterial-viral regulatory networks

• Studying the evolution of bacteria-virus cooperation

• Detailed characterization of inter-phage regulatory circuits

• Understanding the mechanisms that uphold poly-lysogeny in L. monocytogenes

• Development of therapeutic approaches targeting bacteria-virus interactions

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Scientific Impact​

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• Understanding of bacteria-phage evolution and adaptation

• Development of new concepts in host-pathogen interactions

• Discovery of new mechanisms in bacterial gene regulation

• Identification of novel therapeutic targets

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Why Join Our Lab?

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Our research offers unique opportunities to:

• Work at the intersection of virology, bacteriology, and host-pathogen interactions

• Learn cutting-edge molecular techniques and bioinformatics approaches

• Contribute to fundamental discoveries with therapeutic potential

• Develop expertise in multiple fields including molecular genetics, protein biochemistry, and infection biology

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Available Positions

• PhD and post-doc positions

• Master's research opportunities

• Academic year research projects

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We're always looking for motivated students who are:

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• Passionate about science

• Eager to learn new things

• Good team players

• Creative problem solvers

• Dedicated to research​

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Let us know if you want to learn more about our exciting research opportunities!

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​​​​​​​We are in the NEWS!

• An interview in Hebrew describing our work.

• Ynet introducing our work (in Hebrew)