Systems Biology of Mitosis

In humans we do not have a comprehensive understanding of the cell division process, one of the most fundamental functions of life. To address this, we take a comprehensive approach to cell division at the genomic, proteomic, and cellular systems level. After identifying most human genes required for mitosis by high throughput microscopy (www.mitocheck.org), we have developed imaging based in vivo proteomics technology to systematically characterize the abundance, subcellular distribution, and interactions of all mitotic proteins in live dividing cells. The imaging technologies for cellular systems biology are generic and we constantly disseminate them to the scientific community by open source software, practical courses, as well as by giving open access to them in EMBL’s Advanced Light Microscopy Facility, and eventually commercializing them with industrial partners.

Structure of the Nucleus

Understanding how the genome is organized and compartmentalized inside the cell is fundamental to understand how it functions, can be duplicated and passed on to the next generation. Our research on structure and biogenesis of the nucleus currently focusses on the biophysical characterization of the native structure and dynamics of chromosomes, the structure and assembly of the nuclear pore complexes, and the targeting mechanism of membrane proteins to the nuclear envelope. These studies are carried out in cultured mammalian cell lines and also serve to develop new imaging technologies with higher resolution and more direct mechanistic insight into protein function.

Biology of Oocyte Meiosis & Embryonic Mitosis

In humans and mammals in general the formation of an egg from an oocyte and the preimplantation development of the embryo occur by subsequent meiotic and early embryonic mitotic divisions, which are very poorly understood, especially because they normally take place deep inside the body. A better understanding of this process is of fundamental importance since errors in oocyte meiosis and early embryonic mitosis are leading causes of infertility and congenital disease in humans that increase with age. We have therefore established mouse oocytes and early embryos as a model system to apply our high-resolution and high-throughput imaging technologies and combine them with rapid loss of function experiments to investigate the molecular mechanism of these crucial cell divisions and understand why they are so error-prone. To be able to observe these very light-sensitive first stages of mammalian life, we are developing new, more light efficient imaging technologies that allow higher resolution analysis at low illumination energy.