Research

We are interested in how the human cell cycle is regulated, especially in the context of stress to cells. The cell cycle is driven by periodic fluctuations in protein levels and enzyme activities. These fluctuations are coupled together, in analogy to a set of falling domino bricks. When a set of domino bricks are falling, the movement can only go in one direction and once started, it is bound to continue until the last brick has fallen. However, if you artificially block the movement, for example by removing a brick that is about to fall, you need to actively push on the next brick to re-start the movement. Similarly, the cell cycle is interrupted by the presence of DNA-damage. When the damage is repaired, cell cycle proteins that normally are redundant become essential to re-start cell cycle progression. At the same time, some cell cycle activities need to be present throughout a DNA-damage response to retain a cells ability to later re-start. We have three main lines of research to study the molecular regulation of the cell cycle and how DNA-damage and cell cycle signaling affect each other:

First we are interested in the regulation of G2 phase. Why does it exist? How are the transitions from S to G2 and from G2 to M controlled? We are using a micropattern-based approach to study how the signaling network that promotes progression through G2 and entry into mitosis is regulated, with an eye on timings, kinetics and localizations. Experimental data is fitted into mathematical models to help understand G2 phase and to make testable predictions on how signaling regulates the cell cycle.

Second, we are interested in how DNA-damage signaling blocks and subsequently allows resumption the cell cycle, especially in G2 phase. We develop probes to follow DNA-damage responsive kinases in time and space, from initiation of a checkpoint to mitotic entry after recovery from the checkpoint.

Third, we are interested in how DNA-damage and cell-cycle signaling affect each other in order for a cell to remain competent to eventually recover from a checkpoint.