In the modern age, a grand challenge is to shift the focus from defining biological parts to understanding how biological function emerges. The cell division cycle drives vital biological functions including tissue proliferation, homeostasis, and differentiation. It is foundational for all life technologies including agricultural biotechnology, regenerative medicine, and synthetic biology. Accurate control of the cell cycle requires the precise timing and coordination of a complex sequence of molecular events. Surprisingly, our current understanding of these events has been assembled in piecemeal fashion by interrogating one or two molecular components at a time, in different laboratories, using different cell lines. Moreover, most of our knowledge comes from bulk measurement techniques such as immunoblotting that represents the average behavior of large cell populations. As a result, we currently have no comprehensive model of the human cell cycle that can predict the consequences of developmental, genetic, or chemical perturbations; in addition, we have little understanding of how the cell cycle is orchestrated differently among cell types or tissues. In this proposal, we describe a combined experimental and computational approach to assemble a real-time “map” that will reveal the precise order of cell cycle events, their rates of change, cellular locations, and molecular interdependencies. To build the map, we will use a novel computer algorithm that assembles time-lapse fluorescent images of asynchronously dividing cells into a continuous molecular timeline. We will apply the model to study differences in key cell cycle parameters such as speed and timing of molecular events among adult cell types. This effort will produce the first comprehensive, interactive cell cycle model that could alter our understanding of this basic process and have immediate impact on disparate fields such as synthetic biology and disease research.
|Effective start/end date||7/1/15 → 6/30/19|
- WM Keck Foundation
Cell Cycle Checkpoints