Sjors Scheres

Cryo-EM structure determination of amyloid filaments from neurodegenerative disease
Group Leader page

We are looking for an exceptional PhD candidate to join the Scheres group on a project that will be executed in close collaboration with the Goedert group (also at MRC-LMB). The project involves cryo-electron microscopy structure determination of amyloid filaments related to various neurodegenerative diseases. An illustrative example of what we aim to achieve is our recent cryo-EM work on the structures of tau paired-helical and straight filaments from the brain of an Alzheimer patient (Fitzpatrick et al, 2017). The project will involve a combination of brain tissue-derived, and in vitro assembled over-expressed material to analyse the multiple structural conformers that amyloid filaments can adopt in a range of neurodegenerative diseases. These filaments will be analysed using our world-leading cryo-electron microscopy infrastructure and software. Thereby, this project represents an excellent learning opportunity in both (amyloid) protein biochemistry and cryo-electron microscopy.


References:

A.W.P. Fitzpatrick, B. Falcon, S. He, A.G. Murzin, G. Murshudov, H.J. Garringer, R.A. Crowther, B. Ghetti, M. Goedert & S.H.W. Scheres (2017)
Cryo-EM structures of tau filaments from Alzheimer's disease
Nature, 547, 185-190

He & S.H.W. Scheres (2017)
Helical reconstruction in RELION
J. Struct. Biol., 198, 163-176