Research Overview

The ongoing evolutionary arms race between prokaryotes and their viruses has generated a remarkable diversity of molecular systems that interact with and modify nucleic acids or proteins. These ancient defense and counter-defense mechanisms are central to microbial survival and represent a deep reservoir of molecular innovation. Our lab explores how these systems originate, evolve, and function, with a particular focus on their potential as sources of new biotechnological tools. By integrating single-molecule biophysics, cryogenic electron microscopy, biochemistry, and in vivo assays, we uncover fundamental principles of immunity and translate them into technologies for genome manipulation, biotechnology, and medicine.

Mechanisms of novel prokaryotic defense systems

Evolutionary origin of immune mechanisms

Molecular tool development

We investigate specific newly discovered immune systems in bacteria and archaea, focusing on the molecular machines that underpin their antiviral activity. In particular, we study proteins with helicase, nuclease, and/or protease functions to understand how they detect, process, and neutralize invading genetic material. Using structural biology, biochemistry, bacteriophage infection assays, and single-molecule approaches, we dissect how these complexes achieve recognition, specificity, and regulation. These mechanistic insights not only expand our understanding of microbial biology but also establish a foundation for engineering defense systems as versatile molecular tools.

Prokaryotic defense systems not only protect bacteria and archaea against viruses, but also represent the evolutionary foundation of many eukaryotic immune mechanisms. Microbes pioneered many of the molecular strategies now central to immunity, from nucleic acid cleavage to RNA-guided recognition. We investigate how these systems evolved and spread among bacteria and archaea, and how they were later repurposed into the innate immune pathways of eukaryotes. To address these questions, we combine comparative genomics and phylogenetics with experimental biochemistry and structural biology. By reconstructing evolutionary trajectories, we can reveal how simple microbial defense modules were co-opted and refined into the complex immune responses seen in eukaryotes.

Many transformative technologies in modern biology, such as restriction enzymes and CRISPR–Cas systems, were first discovered as components of microbial defense. Building on this tradition, our lab harnesses the diversity of nucleic acid–modifying enzymes for tool development. We characterize candidate proteins biochemically and structurally, and then engineer them for improved stability, activity, or programmability. Our goal is to expand the molecular toolbox available for genome manipulation, and nucleic acid detection. Through collaborations with biotechnology and medical researchers, we aim to translate basic discoveries into applications that advance both fundamental research and therapeutic innovation.