Objectives

The goal of this Research Training Network (RTN) is to gain a better understanding of the regulated dynamics of cell division in higher eukaryotes and to train early-stage and experienced researchers in this field. The RTN focuses on the study of the interplay between regulators (e.g. kinases, phosphatases) of cell division and the mechanical parts of the spindle, mostly molecular motors and other factors modulating microtubule dynamics that are involved in spindle assembly and function. The RTN intends to understand the role of localized activities of regulating enzymes, and to understand how cell cycle checkpoints are coordinated. Finally the RTN intends to discover small molecules with a potential for being more efficient and more specific against proliferation-related human diseases, for example, cancer. The RTN will train researchers to be able to use a combination of approaches ranging from genetics to organic chemistry and mathematics.

Summary of major goals

1. Proteomics and genomics: Topology of the mechano-regulatory network driving cell division
   

   Identification of interaction partners and substrates of mitotic regulatory kinases, molecular motors and microtubule-associated proteins in human tissue culture cells, Xenopus egg extracts, Drosophila embryos and budding yeast.

2. New tools to monitor the dynamics of molecular events in complex cell biological networks.

   Development of novel light microscopy-based assays to monitor the activity of molecular motors, kinases and other spindle components and to monitor protein-protein interactions in cultured cells and in cell extracts.

3. Small molecules from chemical libraries as novel tools to dissect spindle dynamics and as candidates for novel anti-cancer drugs.
   

   Synthesis of chemical libraries of small organic compounds that can serve as specific inhibitors or artificial substrates for mitotic kinases and motor proteins. Identification of small molecule inhibitors of mitotic motor proteins and mitotic kinases.

4. Quantitative understanding of cell division:

   Further development of models for microtubule assembly/disassembly, interactions with motor proteins and for the cell cycle including spatial control of regulatory molecules and development of models