Research interests

The genome of eukaryotic cells is compartmentalised inside the nucleus, delimited by the nuclear envelope [NE] whose double membranes are continuous with the ER. The NE is perforated by nuclear pore complexes [NPCs], which mediate selective traffic between nucleus and cytoplasm. In M-phase, most metazoan cells reversibly dismantle the highly ordered structure of the NE. Nuclear membranes that surround chromatin in interphase are "replaced" by cytoplasmic spindle microtubules, which segregate the condensed chromosomes in an 'open' division. After chromosome segregation the nucleus rapidly reassembles.The overall aim of our research is to elucidate the mechanisms underlying cell cycle remodelling of the nucleus in live cells. Breakdown and reassembly of the nucleus and the formation and correct movement of compact mitotic chromosomes are essential but poorly understood processes. Objective of our future work is to gain further mechanistic insight into nuclear remodelling in live cells. In particular, we are focusing on the mechanism of nuclear growth in interphase, nuclear disassembly and reformation as well as chromosome condensation and positioning in somatic cells and microtubule-independent chromosome motion in oocytes. To rapidly obtain quantitative data from intact cells, we automate and standardise advanced fluorescence microscopy assays. This enables us to apply them in high throughput to all relevant proteins and achieve a systems level understanding of the transformations in nuclear structure during cell division. For example, we have developed high-throughput live cell imaging in combination with RNAi screening to identify novel genes that function in the above cell division processes.

 

Methods applied

We are using somatic mammalian cultured cells and oocytes from mouse and starfish as biological model systems. In these live cells, we are assaying fluorescently tagged structural proteins and their regulators using advanced fluorescence microscopy methods coupled to computerized image processing and simulations to extract biophysical parameters and build mechanistic models.