Friday, November 22, 2024
11/22/2024
Protein synthesis governs if, how fast, and how many times cells divide. Yet how protein synthesis is linked molecularly with cell division is unknown. We will use budding yeast as a model system to answer this problem because yeast has unique properties suited for genetic and biochemical studies. In the previous period, we identified transcripts that engage with the protein synthesis machinery, the ribosomes, in the process of translation in synchronously dividing cells that maintained the physiological coupling of protein synthesis with their division. We will leverage these findings to tackle the long- standing problem of protein synthesis requirements for cell division. In Aim 1, we will identify how translational control of lipogenesis impinges on nuclear morphology. We propose experiments to test the idea that translational control of lipid synthesis, together with lipid-transfer proteins, impact specific parts of lipid metabolism, to control the morphology of the nucleus in the cell cycle. We will also measure the changing levels of lipids in the nucleus during cell division. In Aim 2, we will determine how outputs of one-carbon metabolic pathways change in the cell cycle and respond to translational control. Our data point to the critical roles of enzymes that are part of the folate-based, one-carbon metabolism. We will identify how protein synthesis controls the expression of enzymes of one-carbon metabolism. We will also measure how the different metabolite inputs and outputs of one-carbon metabolic pathways are allocated at distinct points in the cell cycle. Overall, the research we propose will reveal fundamental links between cell growth, protein synthesis, and cell division, enabling novel therapeutic interventions in proliferative diseases.
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