During mitosis chromosomes are segregated with high precision to generate two identical daughter cells. Any error in the process of mitosis has disastrous consequences for the organisms. During embryonic development most of these errors will be lethal and result in miscarriage or still birth, in other cases they can cause severe genetic conditions such as Prader-Willi-Syndrome, lymphoma, leukemia or cancer. The process of segregation is driven by a dynamic bipolar spindle, of which the main building blocks are microtubules. Interestingly, while the mitotic spindle persists over many minutes and sometimes hours, the individual microtubules only have an average lifetime of about 10s, requiring a constant control of the maintenance of the overall structure.
Our current understanding of spindle architecture is mainly based on a manifold of information derived from light microscopy with very limited insights about detailed spindle ultrastructure. It is however the detailed ultrastructure obtained by 3D electron tomography, providing a single microtubule resolution, which is important for our understanding of spindle mechanics. Detailed biophysical models of how the spindle forms and functions can be formulated based on this ultrastructure, which delivers definite numbers and information on length, position, orientation and interaction. We have recently shown for the C. elegans embryo that a combination of spindle reconstructions by 3D electron tomography and light microscopy provides novel insight into spindle mechanics revising our current view of mitosis. Despite the long history of mitosis research there are controversial opinions on how spindles assemble. We are interested in uncovering and understanding the underlying principles of the assembly of mitotic spindles , the structure function relation and the basics of the huge variability of spindle size, architecture and mechanics between different tissues as well as different species. In particular we are very interested in the adaptation of spindle architecture and function during cell differentiation.
We are using a combination of large scale 3D reconstruction of spindles by electron tomography and state-of-the-art light microscopy to investigate the mechanisms and principles of spindle assembly and chromosome segregation. Ultimately we are using the dynamic and ultra structural data to develop and test models of spindle formation and mechanics.
There are two possible tasks that students joining the lab could participate in.
1) Learning the sample preparation for electron microscopy. This would include high-pressure freezing of samples, freeze substitution, embedding in plastic resin, section and finally image acquistion on the electron microscope
2) Image processing, segmentation and analysis of tomograms acquired on the electron microscope. This will include the reconstruction of tomograms, segmentation of microtubules, generation and analysis of 3D models
General enthusiasm and fun working on scientific problems
1) Get a much better understanding of mitosis and cell division
2) A broader knowledge of electron tomography
3) Learn how to do ask questions, design experiments