Evolution of regulatory networks that coordinate Streptomyces multicellular development and life-cycle

• Applicant: Professorin Dr. Natalia Tschowri
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 503748399

Streptomyces are renowned for their prolific production of antibiotics and are also one of the premier models to study bacterial multicellularity. Their complex life-cycle begins with the germination of unigenomic spores and is followed by the growth of hyphal filaments via tip extension and lateral branching that gives rise to a large interconnected mycelial network of foraging hyphae. Upon resource exhaustion, part of the colony differentiates, via a division of labour, into aerial mycelia that produce long strands of environmentally resistant spores. Recent advances have elucidated many of the key regulatory mechanisms that drive Streptomyces multicellular development. However, we still lack an understanding of the evolution of multicellular novelty, the mechanisms that coordinate multicellular life-cycles and life-histories and the ecological factors that select for transitions between multicellular morphologies. Our broad objective in this program is to address these questions in the multicellular Streptomyces. During the first funding period, we integrated molecular and evolutionary approaches to understand causal links between multicellular development and colony life-cycle. Using experimental evolution, we uncovered strong interdependencies between colony size, architecture and life-history. Most strikingly, molecular changes that affect these traits are driven by highly pleiotropic mutations in key global regulators of Streptomyces development, including c-di-GMP signalling and quorum sensing components, that affect the timing and spatial pattern of expression of 100s of genes. Our aim in this second funding period is to analyze the functional and evolutionary consequences of these global changes by combining detailed molecular genetic and biochemical insights with approaches from microbial ecology and evolution to characterize fitness, network dynamics, division of labour and bet-hedging. This highly novel bacterial Evolutionary Developmental Biology (Evo-Devo) approach therefore promises a step change in our understanding of Streptomyces multicellularity and life-cycles, thereby significantly contributing to achieving the goals of this SPP priority program.

• DFG Programme: Priority Programmes
• Subproject of: SPP 2389: Emergent Functions of Bacterial Multicellularity
• International Connection: Netherlands
• Co-Investigator: Professor Daniel Rozen, Ph.D.