Protein interactions regulating the microtubule cytoskeleton

Lay summary

The microtubule cytoskeleton controls fundamental cellular processes including mitosis, cell polarity, and intracellular transport. Because of its importance in all these vital processes, microtubule networks are further implicated in several human pathological conditions including cancer. In cells, microtubule associated proteins interact with the microtubule cytoskeleton to regulate its diverse activities both spatially and temporally during the cell cycle. To understand in detail the molecular mechanisms of these proteins and their interplay is of considerable importance both in health and disease and represents a major challenge. In this proposal we plan to work on three subprojects related to the microtubule cytoskeleton:

1. Structure-function relationship of microtubule plus-end tracking proteins

2. Mechanisms of centriole formation

3. Mechanisms of tubulin modifying enzymes

The aim of the project is to provide detailed quantitative (equilibrium, kinetic), structural (high and medium resolution) and functional information for understanding the proteins and their interaction networks involved in the three subprojects at the molecular level. To reach this goal we plan to use X-ray crystallography in combination with biochemical and biophysical methods. In collaboration, we furthermore will use cell biological methods to test emerging concepts derived from in vitro experiments directly in different cellular systems. Our proposed work will provide novel insights into the molecular mechanisms of several key proteins centrally involved in the regulation of the microtubule cytoskeleton.