NSF-BSF: The Molecular Foundation of Calcium Signaling and Deposition in Bacterial Development

This project addresses a fundamental question in biology: how single bacterial cells come together to form organized, cooperative communities. By uncovering how calcium, a key environmental factor, coordinates this transition, the research will advance our basic understanding of how living systems organize, communicate, and adapt. These insights may reveal new principles that are likely shared across many organisms. The outcomes have clear importance for national health for several reasons. The work is focused on biofilm formation in a bacterial pathogen, Pseudomonas aeruginosa, a major cause of chronic and hard-to-treat infections. When this bacterium forms biofilms, it becomes resistant to antibiotics and the immune system. By identifying how calcium signaling controls biofilm formation, this work may identify new, non-antibiotic strategies to prevent or disrupt infections and help address the growing challenge of antibiotic resistance. The project also supports national prosperity and welfare by informing applications beyond medicine. Biofilms play roles in water systems, energy production, agriculture, and manufacturing. A better understanding of how to control or harness these communities could lead to improved biotechnological processes, more sustainable technologies, and innovative materials inspired by natural systems. In addition, the research will contribute to education and workforce development. It will provide hands-on training opportunities for students at multiple levels, equipping them with skills in modern biological techniques, data analysis, and critical thinking. By integrating research with teaching and outreach, the project will help prepare the next generation of scientists and informed citizens. Overall, this project will generate knowledge that advances science, benefits society, and contributes to the nation’s health and economic vitality. This project advances NSF's priorities in Biotechnology and Advanced Manufacturing. Most bacteria in natural environments exist as biofilms--complex multicellular communities comprised of cells embedded within a self-produced extracellular matrix--that enable survival and dissemination of bacteria. Understanding the molecular fundamentals of biofilm development is critical for both beneficial and detrimental biofilm-associated challenges in ecology, industrial applications, and human health. The proposed research will elucidate the molecular mechanisms and the physiological significance of calcium (Ca) signaling and deposition in biofilm development of Pseudomonas aeruginosa, an exceptional model for studying biofilm biology. Although the increasing body of research highlights the importance of Ca in bacterial life, the molecular basis is vastly understudied. Guided by their prior studies, the research team hypothesizes that (1) integrated Ca and cyclic nucleotide signaling guides functional specialization within Pseudomonas aeruginosa biofilms, and (2) specialized cell subpopulations are responsible for the spatiotemporal organization of Ca deposition, which controls the production of biofilm matrix components. These hypotheses will be tested, using state-of-the-art genetics, transcriptomics, and high-resolution imaging approaches, with the aim of deciphering how biofilm development is controlled by Ca homeostasis and signaling, spatiotemporal organization, and interplay with nucleotide signaling. This study will generate new knowledge on Ca signaling and mineralization in the transition from unicellular to multicellular states during biofilm development with potential implications for advancing biotechnology, materials, and manufacturing. This collaborative US/Israel project is supported by the US National Science Foundation and the Israeli Binational Science Foundation. 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. NSF Award ID: 2536200 | Program: 01002627DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Marianna Patrauchan | Institution: Oklahoma State University, STILLWATER, OK | Award Amount: $1,027,744 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2536200 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2536200.html