Mitosis represents a highly ordered sequence of events that are individually controlled at the nanometer level. Mitosis is essential for eukaryotic life as it drives both propagation of species as well as growth and development of individual organisms. However, mitosis also underlies a number of pathologic processes, all characterized by unregulated cellular proliferation. Not surprisingly, the mitotic apparatus has served as a target for the development of anti-proliferative drugs for over 50 years and thus represents a process of immense clinical relevance. We believe therefore, that understanding how those molecular motors that drive mitosis function at the nanometer level will not only provide scientific insights into the process of mitosis, but will also provide us with the tools needed to control this vital cellular function for human benefit. Regulating how and when stem cells differentiate, controlling the degree of vascular smooth muscle proliferation in the coronary arteries following balloon angioplasty, inhibiting glial proliferation and scar formation in diabetic retinopathy, and blocking proliferation of malignant brain tumor cells within the milieu of a post-mitotic brain are all examples of how the ability to control the function of mitotic motors could lead to new therapies for a host of human diseases. In this application, we propose to form a consortium of investigators whose combined expertise ranges from fabrication at the nanometer level to the molecular genetics of mitotic motor expression to the conducting of phase I and phase II clinical trials. The formation of this consortium should therefore allow us to make rapid progress-not only in our understanding how mitotic motors work at the nanometer level, but also in the development of new ways of regulating their function for the treatment of human disease.
