Regulation of Cell Size in Animal Cells
To understand the process of growth control in animal cells we developed a method, ergodic rate analysis (ERA), to calculate dynamics from samples of fixed cells. Using this new tool, we investigated the dynamics of cell growth during cell cycle and found that cell size is regulated by negative correlation between growth rate to cell size at G1-exit. Proceeding from that point, we asked: what is the mechanism for cell size specification? To answer this question we developed means to directly measure size in living cells. In collaboration with Novartis, we combined our method of interrogating cell growth with a screen of small molecules that have known molecular targets. Because our aim was to identify targets involved in cell size specification, we asked which of the screened compounds affects size variability and at which cell cycle stage. Not surprisingly, many of the identified compounds were found to be inhibitors of mTOR. Following up on that lead, we show that mTOR inhibition decouples the rate of cell growth from cell size, impairing the efficiency of cell size specification and increasing variability.
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