Our long-term research goal is to understand how cells couple their growth with their division. Knowing which (and how) cellular growth pathways affect the machinery of cell division will allow modulations of cell proliferation because such processes dictate how fast cells multiply. To address this problem, we use baker’s yeast as a model organism. This microbe has several useful properties, ideally suited to our research objectives: First, in yeast initiation of cell division is coupled to the formation of a bud. Hence, one can monitor the timing of initiation of division by phase microscopy. Second, yeast can grow in steady-state continuous cultures. This allows for precise control and monitoring of metabolic parameters. Third, yeast is a genetically tractable eukaryote. It has a machinery of cell division that is very similar to that of human cells.

Protein synthesis and cell division

Protein synthesis underpins much of cell growth and determines the rate at which cells proliferate. A major objective of our research is to define how protein synthesis modulates the division of cells. Understanding the role of protein synthesis during cell division will provide insight into the initiation of new cell cycles, the speed of these cycles, the number of successive cell cycles, and the coordination of cell proliferation with the available nutrients. These cellular decisions are often dysregulated in disease.

H. M. Blank, R. Perez, C. He, N. Maitra, R. Metz, J. Hill, Y. Lin, C. D. Johnson, V. A. Bankaitis, B. K. Kennedy, R. Aramayo, M. Polymenis, Translational control of lipogenic enzymes in the cell cycle of synchronous, growing yeast cells. EMBO J. 36, 487–502 (2017).

Translational control in ribosomal protein mutants

Ribosomes are large machines that make all the proteins in cells. About 80 different proteins are also parts of the ribosomes themselves. For some ribosomal proteins, the genetic information to make them exists in almost identical copies. Hence, all ribosomal proteins are parts of the same machine. While these proteins can be very similar, mutating each can lead to very different outcomes. From microbes to people, mutations in ribosomal proteins change the biology of those organisms in profound and varied ways. When it comes to ribosomal proteins, the old saying “you’ve seen one, and you’ve seen them all” can be misleading. For example, yeast lives longer if some ribosomal proteins are missing, but dies in the absence of others. Figuring out how ribosomal protein mutations have such effects is critical. It will shed light on the ways that protein synthesis controls how organisms function in normal and disease conditions.

N. Maitra, C. He, H. M. Blank, M. Tsuchiya, B. Schilling, M. Kaeberlein, R. Aramayo, B. K. Kennedy, M. Polymenis, Translational control of one-carbon metabolism underpins ribosomal protein phenotypes in cell division and longevity. eLife 9 (2020).

Abundances of biomolecules in the cell cycle

Recognizing molecular landmarks in the cell cycle is a valuable, and often necessary, step for deciphering how and why cell cycle pathways are integrated. For the first time in any system, we generated comprehensive datasets for RNAs, proteins, metabolites, and lipids, from the same samples of yeast cells progressing synchronously in the cell cycle. We found that the cellular lipid profile is highly cell-cycle-regulated, with triglycerides and phospholipids peaking late in the cell cycle, together with protein levels of ergosterol biosynthetic enzymes. This highlights the importance of integrating multiple ‘omic’ datasets to identify cell cycle-dependent cellular processes.

H. M. Blank, O. Papoulas, N. Maitra, R. Garge, B. K. Kennedy, B. Schilling, E. M. Marcotte, M. Polymenis, Abundances of transcripts, proteins, and metabolites in the cell cycle of budding yeast reveal coordinate control of lipid metabolism. Mol. Biol. Cell 31, 1069–1084 (2020).