Sjors studied chemistry at Utrecht University, The Netherlands, where he
also obtained his PhD in protein crystallography. He was a post-doc in
the group of Jose-Maria Carazo in Madrid, before he started his group at
the LMB in 2010. His main interest is currently in the development of
new methods for high-resolution cryo-EM structure determination and in
the cryo-EM structure determination of amyloid fibrils.
The assembly of microtubule-associated protein tau into abundant filamentous inclusions underlies many neurodegenerative diseases called tauopathies. Tau inclusions display distinct neuroanatomical and cellular distributions between different tauopathies. Morphological and biochemical differences suggest that tau filaments adopt disease-specific molecular conformations. There are six tau isoforms - three isoforms with four microtubule-binding repeats each (4R tau) and three isoforms lacking the second repeat (3R tau). This gives rise to tauopathies with filaments composed of only 3R tau, only 4R tau
or both 3R and 4R tau. Molecular conformers of filamentous tau may give rise to different neuropathological phenotypes, similar to prion strains, but the underlying structures are not known. Using electron cryo-microscopy (cryo-EM), we previously determined the structures of tau filaments from Alzheimer’s disease, which contain both 3R and 4R tau. More recently, we also determined the structures of tau filaments from Pick’s disease and show that they define a second tau protein fold consisting of residues K254-F378 of 3R tau, thereby proving the existence of molecular tau conformers. I will present both folds and discuss how they explain differences in isoform incorporation and phosphorylation observed between Alzheimer's disease and Pick's disease.