ASSOCIATED MAJORS:

1. LIFE SCIENCES AND MEDICINE

• Biology

1. NATURAL SCIENCES

• Chemistry

PROJECT TITLE:

Tubulin conformational changes related to GTPase activity

PROJECT SUMMARY. Description of activities and objectives:

Tubulin is a GTPase responsible for key functions during cell growth and division through its self-assembly into hollow cylinders called microtubules. Perturbation of microtubules’ function is an essential target in cancer and neurodegenerative diseases chemotherapy.
In microtubules, GTP hydrolysis triggers lattice structural changes needed for their dynamics. The development of drugs able to smoothly modulate MTs requires in depth understanding of the molecular mechanism underlying tubulin on/off transition switch inside the MTs and its dependence on the nucleotide-bound state. Currently, we focus on increasing our understanding of those changes studying tubulin and microtubules in different nucleotide-bound states and under native conditions or in the presence of new Microtubules Stabilizing Agents (MSAs) or Microtubules Destabilizing Agents (MDAs).

The student will be involved in: the production of the target proteins with the quality required for high-resolution structural studies (X-ray crystallography and electron microscopy); setting crystallographic screening and optimization experiments and analysis of subsequent datasets; preparing electron microscopy samples and grids visualization and; biochemical analysis of protein ligand interaction using different biochemical approximations.

https://www.cib.csic.es/