Novel Mechanisms Linking Nucleoid Condensation and Stress Survival in a Model Extremophile

Microorganisms are essential to modern biomanufacturing, where they are engineered to produce fuels, chemicals, and medicines. However, industrial production processes expose microbes to harsh conditions that reduce their performance and reliability; these include oxidative stress, and nutrient limitation. A major barrier to advancing biomanufacturing is the limited understanding of how cells sense and physically reorganize their genetic material to survive these stresses. This project focuses on a remarkable bacterium, Deinococcus radiodurans, which can withstand extreme environmental conditions that are lethal to most life. By uncovering how this organism reorganizes its genome to survive stress, this research addresses a fundamental question in biology: how the structure and organization of genetic material enable cells to function under extreme conditions. The outcomes of this research will lay the scientific foundation for engineering more robust microbes capable of maintaining function in industrial environments, thereby advancing the nation’s capacity for sustainable and resilient biomanufacturing. In addition, the project will train students and postdoctoral researchers in interdisciplinary approaches spanning molecular biology, engineering, and data science, while providing opportunities for engagement with industry and career development. Together, this work will both expand fundamental scientific knowledge and contribute to a highly skilled workforce prepared to advance the U.S. bioeconomy. The specific goal of this project is to elucidate the molecular mechanisms that link nucleoid condensation to stress survival in Deinococcus radiodurans. The central hypothesis is that recently uncovered RNA-binding proteins regulate genome organization in response to stress through coordinated control of DNA architecture and gene expression. To test this hypothesis, the project will pursue three objectives: (1) define how these proteins modulate nucleoid condensation under stress conditions using quantitative microscopy and image-based analysis; (2) determine how these proteins alter transcriptional and genome accessibility landscapes using high-throughput sequencing approaches; and (3) establish mechanistic links between genome organization, gene regulation, and cellular survival through integrative systems-level analysis. This work employs a multidisciplinary approach combining advanced microscopy, synthetic biology, and genome-wide sequencing to generate a comprehensive mechanistic framework connecting RNA-binding proteins, genome architecture, and stress resilience in an extremophilic bacterium. The expected outcomes include new insights into how cells dynamically reorganize their genomes in response to environmental stress, identification of regulatory proteins with dual roles in structural and gene regulatory processes, and datasets and tools that will be broadly accessible to the research community. Overall, we expect these research contributions to establish foundational principles for engineering stress-resilient microbes, thereby enabling future innovations in microbial biomanufacturing and synthetic biology. 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: 2546044 | Program: 01002627DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Lydia Contreras | Institution: University of Texas at Austin, AUSTIN, TX | Award Amount: $1,137,205 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2546044 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2546044.html