Metabolic Coupling During Bacterial Development

ongoing

Studies on developmental biology have traditionally focused on deciphering the signaling and regulatory networks that control cellular differentiation. However, it remains unclear how the interplay between developmental regulatory circuits and housekeeping metabolism contributes to the determination of cell fate. Here, I aim to provide a comprehensive analysis of the role of housekeeping metabolic functions during endospore formation in the bacterium Bacillus subtilis. Sporulation is a simple developmental pathway that entails the interaction between two cells arising from a single cell division: the forespore, which becomes the metabolically dormant spore, and the mother cell, which dies after sporulation. The mother cell and forespore activate different genetic programs, leading to the production of sporulation-specific structural proteins necessary for proper spore development. However, little is known about how essential housekeeping functions contribute to the process of sporulation. I have developed a system to degrade proteins catalyzing key metabolic reactions in a cell- and developmental stage-specific manner during sporulation. Here, I will use this system to perform a genome-wide study to evaluate the role that housekeeping metabolism plays in spore development. My preliminary results provide evidence for metabolic differentiation between the mother cell and the forespore, metabolic dependency of the forespore on metabolic precursors synthesized in the mother cell, and bidirectional transport of phospholipids between the mother cell and forespore membranes. I will use a combination of cutting edge genetic, cell biology and chemical biology techniques to reveal the metabolic transactions that underlie this unique, syntrophic relationship. The successful completion of this project will provide the first exhaustive metabolic description of a developmental process.