Date of Award
2025
Document Type
Thesis
Degree Name
Doctor of Philosophy (PhD)
Thesis Advisor
Luciano Marraffini
Keywords
phage, innate immunity, signaling systems, cyclic nucleotide, abortive infection, sensing
Abstract
Viruses are among the most significant selective pressures shaping the evolution of life on Earth. In the microbial world, bacteriophages (phage) are bacterial viruses and drive a continuous evolutionary arms race that has led to an extraordinary diversity of bacterial defense mechanisms [1]. These systems are thought to have provided the evolutionary foundation for numerous eukaryotic immune strategies [2]. Experimental studies have validated many of these anti-phage defense systems and revealed the mechanisms by which they disrupt phage infection [3]. Nonetheless, major gaps persist in our understanding of how bacterial immune systems recognize bacteriophage infection to trigger immunity. This dissertation examines the molecular basis of this sensing process, offering new perspectives on host–pathogen interactions and illuminating conserved principles of immune defense across domains of life. Our first major discovery revealed that the bacterial Thoeris system, a Toll-interleukin 1 receptor (TIR) domain-based immune system in bacteria, detects specific phage capsid proteins [4]. This recognition event triggers the production of a signaling molecule that activates the depletion of an essential metabolite, limiting viral propagation. The second discovery demonstrated that cyclic oligonucleotide-based antiphage signaling systems (CBASS) recognize infection through the recognition of structured bacteriophage RNAs [5]. These RNAs bind bacterial cyclases, promoting the production of a signaling molecule that activates downstream effectors to mount an immune response. Since CBASS and Thoeris are orthologous to cGAS-STING and Toll-like receptors (TLRs), respectively, in mammalian innate immunity, these findings highlight conserved mechanisms for the activation of antiviral defense pathways across evolutionary domains [1].
License and Reuse Information
This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.
Recommended Citation
Roberts, Cameron Grace, "Ancient Immune Systems: Sensing and Signaling in Bacterial-Phage Conflict" (2025). Student Theses and Dissertations. 839.
https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/839
Comments
A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy