Biology of Aging Journal Club - Prion Tuning Mutagenesis as to Enable Rapid Adaptation - Members +3

Paper Title: Prion-based protein self-assembly tunes mutagenesis to enable rapid adaptation Summary: Mutations supply the raw material for evolution, yet because most are neutral or deleterious, elevated mutation rates are typically transient. Nonetheless, modeling predicts that a mechanism for heritable but reversible ‘‘mutagenesis switches’’ would be advantageous in some selective contexts. Here, we report that frequent prion-based switching of DNA repair and recombination proteins alters mutagenesis in Saccharomyces *cerevisiae *populations from diverse ecological niches, including the laboratory and clinic, providing adaptive benefits in short-term evolution under strong selective pressure. Self-templating protein assembly alters the activities and interactions of multiple DNA-fidelity factors, reshaping adaptive outcomes while maintaining resilience to genotoxic stress. In the WHO priority pathogen Candida albicans, which diverged from *S. cerevisiae *∼300 million years ago, a key regulator of prion inheritance accelerates the rapid emergence of fluconazole resistance. These findings suggest that protein self-assembly can generate epigenetic memory that tunes genome diversification over multiple generations, enabling rapid adaptation in challenging environments. doi.org/10.1016/j.cell.2026.05.018 Location: Hosted in the Conference Room on Floor 8. Moderated and hosted by: Byron P. Lee linkedin.com/in/biobitworks cellico.bio Co-founder of Prohm Life (prohm.life) About Prohm: Biology is wonderfully complex. Our ambition is to connect the steps of protein research, so a good question can travel further. From proposing designs to evaluating structures, planning experiments and learning from results: a connected research loop, with people setting the purpose and making consequential decisions. Hosts: Biopunk Lab (biopunklab.com) It’s alive and kicking. Biopunk is a community of scientists, entrepreneurs, students, and artists playing at the edge of biotech. This event is hosted at the Frontier Tower: We are transforming a 16-floor tower in San Francisco into a self-governed vertical village—a hub for frontier technologies and creative arts. Tier-one labs presenting AI, Ethereum, biotech, neuroscience, longevity, robotics, makerspace, human flourishing, and arts & music. These floors will house innovators and creators pushing the boundaries of human potential in a post-AI-singularity world. Apply here for founding citizenship: frontiertower.io/apply Why should I become a citizen? Be part of creating the first self-governed vertical villageConnect with the most creative people in the cityGet access to all floors, free event space & movement floor Website: frontiertower.io/ Need more reading? Visit frontiertower.notion.site/