Investigating the role of cyclin B1 in early cell division

We would like to investigate what controls the earliest cell divisions. In particular, we will address the role of a specific protein, cyclin B1, that has been implicated as the most important regulator in cell division from work in other systems such as yeast. Thus far we know that mammals cannot develop without cyclin B1, but we don t know why the embryos fail.

The principal aim of this proposal is to enhance our understanding of the role of cyclin B1-Cdk1 in mammalian mitosis, in particular the entry to mitosis and its function in spindle assembly and orientation. The project will use cyclin B1 null embryos derived from a heterozygouse cyclin B1 knockout mouse line to provide cells that lack any cyclin B1. Cyclin B1, wild type and mutants will then be introduced into these cells to study the requirement for cyclin B1 in the cell cycle, for the control of spindle orientation in early cleavage cycles, and to perform a structure-function analysis of cyclin B1. The project builds on observations we have made previously, namely that mammalian tissue culture cells with reduced levels of cyclin B1, induced by siRNA, enter mitosis but show defects in spindle orientation, and that in mouse embryos cyclin B1 siRNA causes cells to fail at the first cell division.