Metabolic foundation of developmental transitions

• Applicant: Dr. Sofia Doello
• Subject Area: Microbial Ecology and Applied Microbiology ; Metabolism, Biochemistry and Genetics of Microorganisms
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 578715661

Dormancy is a widespread survival strategy that enables bacteria to persist during unfavorable conditions. Most bacteria in natural environments are thought to exist in a dormant state, resuming growth only when conditions improve. This strategy has major implications for microbial ecology and evolution, as well as for biomedical research, given its role in pathogen persistence and antibiotic resistance. Understanding the molecular mechanisms that control transitions into and out of dormancy is therefore of broad biological and societal importance. Cyanobacteria represent an excellent model to study these processes. As ancient and ecologically essential primary producers, they have evolved remarkable strategies to cope with fluctuating environments. The unicellular cyanobacterium Synechocystis sp. PCC 6803 survives nitrogen starvation by entering a metabolically inactive state through a highly regulated and synchronous developmental program. The population-wide coherence of this program makes Synechocystis particularly well suited to dissect the molecular basis of dormancy and awakening. The goal of this project is to elucidate the molecular mechanisms that enable successful awakening from nitrogen-induced dormancy, focusing on how the mobilization of stored resources is controlled and how the regeneration of the photosynthetic apparatus is regulated. To achieve this, I will investigate: (1) The regulatory mechanisms that control glycogen degradation during awakening, with a focus on the biochemical, structural, and subcellular localization dynamics of glycogen phosphorylases, as well as the role of protein phosphorylation and redox regulation in the glycogen catabolic pathway. (2) The role of polyphosphate in survival under nitrogen starvation, by combining biochemical and mathematical modeling of key enzymes with physiological characterization of deletion and revertant mutants. (3) The regulatory mechanisms that initiate reassembly of the photosynthetic apparatus, through the identification of transcription factors, kinases, and phosphatases controlling thylakoid biogenesis. By integrating biochemistry, physiology, and systems-level approaches, this work will reveal how cyanobacteria mobilize stored resources and orchestrate photosynthetic recovery. The outcomes will illuminate conserved strategies of bacterial resilience, with implications for microbial ecology, biotechnology, and the fight against persistent infections.

• DFG Programme: Emmy Noether Independent Research Groups
• International Connection: South Africa
• Participating Person: Professor Dr. Jacky Snoep