Physical Principles of Nuclear Division

We are interested in the mechanical principles of chromosome segregation, nuclear transport and positioning during mitosis. Mitosis is fundamental to life as it is the basis for reproduction and growth. In metazoans, rapid and reliable reproduction of the genome in the fertilized egg and genome distribution into thousands of cells is essential for embryo development. We are interested in the physical mechanisms underlying this spatial distribution. In some animal species the cell membrane plays a key role in nuclear positioning. In most insects, however, the early embryo develops in a single large cell (“syncytium”) where nuclear distribution is much more challenging. The mechanical principles and their underlying molecular interactions, which determine nuclear transport and inter-nuclear spacing, are unknown. We use a novel, interdisciplinary approach that overcomes several major obstacles that have thus far hindered our understanding of spindle mechanics. One of the greatest obstacles is the cell membrane that seals the cell and provides a physical barrier, preventing direct access to the spindle for mechanical measurements. By exploiting early Drosophila melanogaster eggs and embryos where mitoses occur without membrane cleavage in a large syncytium, we perform manipulation experiments ex vivo, which allows mechanical, optical and biochemical manipulation, in a genetically tractable organism.