Postdoctoral Fellowship: PRFB: Deciphering the Role of Pyrazine Biosynthetic Enzymes in Host-Colonization Dynamics and Gut Chemical Diversity

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2025. The fellowship supports research and training of the fellow that will contribute to biology in innovative ways. The gut microbiome is made up of trillions of bacteria which play vital roles in human health. While the importance of microbiome is well-established, little is known about how this collection of microbes communicate with each other and the functional consequences of the communication. This project will explore how microbial communication influences colonization of the host gut and contributes to the chemical landscape within the gut. The results will increase general understanding of how bacteria colonize animals and discover new molecules derived from the gut microbiome. These molecules could have useful properties in therapeutic and other applications. As part of the project, the fellow will mentor undergraduate students, graduate students, and postdoctoral trainees through activities that promote academic advancement and career development in the biological sciences. This research focuses on the role of a recently discovered pyrazine-generating enzyme, Pyr, in microbial colonization and chemical diversity within the gut microbiome. Pyr produces signaling molecules known as pyrazine autoinducers, which regulate bacterial behaviors such as biofilm formation, aggregation, and siderophore production – key traits linked to colonization and interbacterial competition. This fellow will employ a combination of genetic recombineering, microscopy, metabolomics, and both in vitro and in vivo colonization models to determine how Pyr-derived pyrazines impact microbial interactions and influence bacterial host-colonization. Beyond their roles in signaling, Pyr homologs are frequently embedded in diverse biosynthetic gene cluster architectures across gut microbes, suggesting that these enzymes contribute to the underexplored chemical repertoire of the gut microbiome. To investigate this potential, the fellow will synthesize predicated amino acid-derived precursors, analyze Pyr-dependent metabolic outputs through publicly available datasets, and characterize the products of Pyr-harboring gene clusters through heterologous expression and structural analysis. Collectively, this work will uncover new functions for Pyr enzymes in microbial signaling and natural product biosynthesis. The fellow will receive interdisciplinary training in microbiology, metabolomics, and chemical biology, and will mentor undergraduate and graduate students through research-based activities focused on experimental design, data analysis, and scientific communication. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.