• Our research lies at the interface of comparative and evolutionary genomics, molecular evolution, and computational structural biology, with a broad interest in understanding how proteins and molecular systems originate, diversify, and acquire new functions. A recurring question is how evolution works with an existing repertoire of protein domains, structural folds, and molecular architectures, modifying, recombining, and repurposing them to generate new biological functions. Comparative analysis across genomes and proteomes provides a powerful framework for reconstructing these processes and for discovering molecular relationships that may no longer be apparent from sequence similarity alone.

 

• A major focus of the group is the discovery and evolutionary analysis of prokaryotic defense systems and phage counter-defense mechanisms. The group seeks to identify previously uncharacterized defense systems and components and to understand how these systems recognize invading genetic material, distinguish self from non-self, deploy effector mechanisms, and regulate their responses. Particular emphasis is placed on the evolutionary provenance and functional repurposing of proteins and domains within these systems. Conserved gene neighborhoods, domain architectures, phyletic patterns, and structural relationships are integrated to uncover new systems, infer their functional organization, and reconstruct their evolutionary histories. Complementing this perspective, the group investigates how phages evolve proteins and molecular strategies that evade, inhibit, or otherwise counteract host defense systems, providing insight into the continuing evolutionary arms race between prokaryotes and their viruses.

 

• This interest in virus–host evolutionary interactions and protein innovation extends to the RNA and DNA viruses of eukaryotes. Here, the emphasis is on the evolutionary origins and structural diversity of viral proteins, particularly how existing protein domains and folds have been recruited and repurposed during viral evolution. Because many viral proteins evolve rapidly and retain little detectable sequence similarity to known proteins, structural and evolutionary approaches can reveal relationships hidden within the vast viral dark matter. Mapping this poorly characterized protein universe can provide clues to the origins, diversification, and possible functions of viral proteins.

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• Across these systems, protein evolution provides a common conceptual thread. The group investigates how duplication and divergence, domain recruitment and recombination, structural conservation, and functional repurposing shape protein families and molecular systems over evolutionary time. Methodologically, the group integrates large-scale comparative genomics, sensitive sequence analysis, phylogenetics, genomic neighborhood and domain-architecture analysis, and computational protein structure analysis. Together, these approaches enable evolutionary relationships to be traced across multiple scales—from individual domains and folds to protein families, genomic systems, viruses, and complete genomes—providing a framework for both the discovery of previously unrecognized molecular systems and the reconstruction of their evolutionary histories. Beyond its major focus areas, the group also applies this evolutionary framework to broader questions in lineage-specific gene-family diversification and receptor–ligand evolution, examining how molecular repertoires expand, diversify, and acquire new functions across evolutionary lineages.​

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Prokaryotic Defense Systems and Phage Counter-Defense

Evolution of Proteins in Eukaryotic RNA and DNA Viruses

Evolution, Recruitment, and Repurposing of Protein Domains and Folds

Lineage-Specific Evolution of Gene Families

Receptor–Ligand Evolution and Functional Diversification