Investigating the binding of MeCP2 on chromatin

MeCP2 is a nuclear protein that binds to methylated DNA in the genome. It is highly abundant in neurons and mutations in the MECP2 gene cause the severe X-linked autism spectrum disorder Rett syndrome. MeCP2 is a DNA binding protein but little is known about how MeCP2 behaves within the context of a chromatinised template.

The aim of this project is to investigate the binding and function of MeCP2 within the minimal building block of chromatin, the nucleosome. Using a combination of cell biology, biochemical and structural biological techniques this project will help to explain how MeCP2 binds to nucleosomes, how this leads to gene repression and how Rett syndrome mutations interfere with these processes. The project will involve:

1) Protein expression and purification of chromatin proteins and histones
2) Chemical biology technologies to generate modified proteins
3) Protein biochemistry and biophysical techniques to understand binding of MeCP2 to modified nucleosome templates
4) Structural biology, in particular cryo-EM, to understand the molecular mechanisms of chromatin interactions
5) Cell biology to extend our in vitro observations to the living cell

The project requires a passionate, motivated student interested in how molecular understanding can help explain fundamental biological processes.

This is a joint project between the Wilson and Bird labs based in the Wellcome Trust Centre for Cell Biology, at the University of Edinburgh. Sources of funding are available for both UK and non-UK students, for more information see our website and get in touch, www.mdwilsonlab.com, http://birdlab.bio.ed.ac.uk/.