EMBL Imaging Centre

Cutting-edge electron and light microscopy technologies

Matthias Schmidt’s story

Matthias Schmidt
PHOTO: Ulm University

Ulm University

Why did you decide to come to EMBL’s cryo-EM service platform?

In our lab we work on the structural analysis of different amyloid fibrils, including fibrils from Alzheimer’s disease. But at the moment our focus is mainly on ex vivo fibrils from systemic amyloidosis (AA-amyloidosis and AL-amyloidosis). I’m working with different amyloid fibrils and I try to reconstruct them at high resolution to create an atomic model.

At our university we have two EMs made by JEOL, which we use for our work, a JEM-1400Plus (120 kV EM used mostly for negative stain purposes) and a JEM-2100F (200 kV EM used for scanning cryo grids). With our setup it is not possible to collect large amounts of high-quality data for reconstructions around 3Å resolution. 

I also had previous experience with EMBL thanks to a collaboration, and Heidelberg is close by, so EMBL seemed like a good choice.

How was your experience at EMBL and did you get promising results?

The samples I’m working with are often unevenly distributed on a grid and in the holes. Wim Hagen helped find a solution to manually pick the sample in an efficient way with SerialEM. This allowed us to obtain a dataset with images of the sample and not a majority (80%) of empty ones. If the sample is good, I get the results I need.

Some of the results were published recently: 

  • Liberta F, Loerch S, Rennegarbe M, et al. Cryo-EM fibril structures from systemic AA amyloidosis reveal the species complementarity of pathological amyloids. Nature Communications 10: 1104 (2019). DOI: 10.1038/s41467-019-09033-z
  • Radamaker L, et al. Cryo-EM structure of a light chain-derived amyloid fibril from a patient with systemic AL amyloidosis. Nature Communications 10: 1103 (2019). DOI: 10.1038/s41467-019-09032-0

What makes the setup at EMBL’s cryo-EM service platform unique?

The flexibility to solve problems and the dedication to getting the best and most data are great. 

If a colleague told you they were considering coming to the EMBL cryo-EM service platform, what would you say?

Yes, go! You will get high-quality data. I don’t know a better place for that. 

Would you come back?

Yes, I’m planning to.