After nearly six decades of groundbreaking work in molecular biology, Richard Losick, the Maria Moors Cabot Research Professor of Biology, has published his final research paper in the Proceedings of the National Academy of Sciences (PNAS). The study, led by former Losick lab postdoc Adnan Syed, sheds new light on the mechanisms by which the pathogen Staphylococcus aureus forms biofilms—multicellular communities that make the bacterium highly resistant to antibiotics and immune defenses.
“Our findings reveal that a decrease in the signaling molecule cyclic-di-AMP triggers biofilm formation,” Syed explains. “Notably, this decrease represses the “accessory gene regulator” or agr system, a well-established negative regulator of biofilm formation.”
Reflecting on the paper’s significance, Losick remarked: “These biofilms confer tolerance to antibiotics and help the bacterium evade the immune system. Importantly, our paper reveals an attractive target (an enzyme that breaks down the cyclic-di-AMP signaling molecule) for therapeutic agents that would block biofilm formation. I spent most of my career investigating a harmless bacterium, B. subtilis. So, it is rewarding to me to have my laboratory make a contribution of potential medical significance.”
Losick’s career began with the publication of a paper based on his undergraduate senior thesis 58 years ago and concludes with this PNAS paper, which holds personal and professional significance. He credits the work to a collaborative effort with colleagues and institutions:
“This PNAS publication is of special significance to me as it closes my career as a microbiologist. Also special to me are the wonderful collaborations that made this final publication possible: Dan Kahne and his former postdoc Erik Van Vlack here in Harvard’s Department of Chemistry and Chemical Biology, Niels Bradshaw – who was once a postdoc in my lab – and his student Rishika Baral at Brandeis University, and Maria Luisa Gil-Marqués and David Hooper at Mass General Hospital. And, of course, the entire effort was led by my former postdoc Adnan Syed, to whom I am especially grateful.”
Though his laboratory has closed, Losick remains immersed in the field of molecular biology, focusing on its early history. He teaches a course on the subject at Harvard and will expand his efforts internationally, including teaching in England this spring. Losick also plans to publish an open-access eBook titled The River Divides into Thousands of Branches, chronicling the origins and development of molecular biology.
With this final contribution to microbiology, Losick leaves an enduring legacy of scientific discovery and inspiration, underscored by a career devoted to understanding the molecular mechanisms of life.
