Dissecting the role of redox signaling in coupling oscillatory metabolism to cell division

• Applicant: Professor Dr. Bruce Morgan
• Subject Area: Biochemistry ; Cell Biology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 505680640

Under specific chemostat growth conditions, yeast cell populations spontaneously synchronize to undergo sustained metabolic oscillations, which appear to be tightly coupled to cell growth and division. Collectively this oscillatory behavior is referred to as the yeast metabolic cycle (YMC). Intriguingly, our lab and others have recently shown that metabolic oscillations persist in the absence of cell division and even seem to be important for gating cell cycle entry and exit. Furthermore, we demonstrated that redox signaling is implicated in the emergence of a stable collective metabolic oscillatory behavior and in the coupling of oscillatory metabolic state to cell division in the context of the YMC (Morgan lab). Recent studies, including extensive preliminary experiments from the Charvin lab, reveal the existence of metabolic, redox signaling, and protein kinase A activity oscillations at the single cell level. Consistent with the YMC, these oscillations can be coupled to cell division and seem to be important for regulating cell cycle entry and exit but can also persist independently of cell division. However, whether metabolic cycles observed at the single cell level correspond to those observed in YMC-synchronized populations is unclear. The mechanistic basis of metabolic cycling in both systems is completely unknown and the exact causal relationships, crosstalk and interplay between metabolic cycles and cell division remain elusive. Now, the Morgan and Charvin labs will combine their expertise to develop a novel methodology that merges population-scale dynamic measurements with microfluidics-based single-cell tracking. Combining our expertise in yeast genetics, novel genetically encoded redox sensors, quantitative live-cell imaging, microfluidics, and chemostat cultures we will elucidate population heterogeneity in terms of metabolic cycling and cell division with thus far unobtainable spatial and temporal resolution. Furthermore, we will address the role of redox signaling and protein kinase A activity in coupling cell division with oscillatory metabolism. By combining our approaches with computational analyses, we will take important steps towards deciphering the fundamental principles that govern the emergence of metabolic oscillations, elucidate their potential fitness advantages under fluctuating environments and understand their relevance for cell division.

• DFG Programme: Research Grants
• International Connection: France
• Major Instrumentation: Optical parts for in house imaging system
• Instrumentation Group: 5040 Spezielle Mikroskope (außer 500-503)
• Partner Organisation: Agence Nationale de la Recherche / The French National Research Agency
• Cooperation Partner: Professor Dr. Gilles Charvin