Mechanisms that Control Cell Division and Cell Growth Douglas Kellogg, MCD Biology Cells show extraordinary diversity in size and shape.  The mechanisms by which cells control their growth and size are poorly understood and represent a fundamental unsolved problem in cell biology.  The goal of our work is to elucidate these mechanisms. Our approach is to use biochemistry, genetics, and mathematical modeling to understand signaling networks that are required for control of cell size and cell growth.  Current projects include the following:

Coordination of Cell Growth and Cell Division

We are exploring a signaling network that is thought to delay entry into mitosis until cells have reached a critical size.   Two key components of the network are the Wee1 kinase, which blocks entry into mitosis by phosphorylating and inhibiting Cdk1, and the Cdc25 phosphatase, which promotes entry into mitosis by removing inhibitory phosphorylation of Cdk1.  We are defining the upstream signals that regulate Wee1 and Cdc25.  This work is has led to new clues to the nature of the long mysterious mechanisms by which cells sense and regulate their size.

Wild type yeast cells	The mutant cells above fail to properly coordinate cell growth and cell division

Functional Dissection of a Molecular Switch

Wee1 and Cdc25 are also key components of a mechanism that triggers switch-like activation of Cdk1.  Thus, another important goal of our work is to understand how Wee1 and Cdc25 integrate information and generate switch-like activation of Cdk1.  Wee1 and Cdc25 are regulated by dramatic cell cycle-dependent changes in phosphorylation.  We have discovered that the phosphorylation states of Wee1 and Cdc25 are determined in a highly dynamic manner by opposing kinase and phosphatase activities.  Theoretical considerations have shown that opposing kinase and phosphatase activities can generate can generate switch-like responses and other powerful signaling behaviors.  We are investigating the molecular mechanisms and the general principles of signaling underlying the Wee1/Cdc25 molecular switch.

Cell cycle-dependent control of cell growth

We discovered that Cdk1 plays a direct and essential role in promoting cell growth early in the cell cycle.  We are currently exploring the mechanisms by which Cdk1 promotes cell growth, and how regulation of Cdk1 may control the extent and rate of cell growth.