Research project

High-coherence, ultracold electron diffraction for molecular movies of membrane proteins

Proteins are the workhorses of life, as they are the molecules that perform all processes of living organisms. Understanding how they work helps to cure diseases. It would therefore be very useful if we could see them, but they are very small and they move extremely fast. In this project, led by Dr. Julius Huijts, we try to develop a kind of microscope with a high-speed camera so that we can film proteins and see how they work.

For this, we have made a special setup that generates extremely short flashes of electrons, so that we can get very quick snapshots of the proteins. These electron flashes also need to be of very high quality, and that is why we generate them from atoms that are extremely cold, close to absolute zero temperature. By combining different snapshots at different moments we plan to reconstitute a molecular movie of the protein.

Duration
September 2022 - March 2025
Partners
Institute for Complex Molecular Systems
Applied Physics and Science Education
Project Manager
O.J. (Jom) Luiten

Membrane proteins are responsible for all traffic and communication between cells. Their misfunctioning is at the heart of a plethora of diseases. But, notoriously difficult to study, they are poorly understood. Cryo-electron microscopy has recently revealed structures of some of these proteins, but as the samples are frozen the obtained images are inherently static.
Now imagine that we could have an instrument that allows to make movies of such proteins, thus unraveling not only their structure but also their function. In this project, we will develop a unique, table-top setup based on the diffraction of ultracold electrons that does exactly that.

We use a source that is unique in the world, that generates pulses of ultracold electrons that are in principle sufficiently short, intense and coherent to enable time-resolved electron diffraction on 2D crystals of membrane proteins. Through a pump-probe experiment we will follow the light-induced conformational change of bacteriorhodopsin, a model membrane protein. This will be the first molecular movie of a protein ever obtained on a table-top setup.

The principle of the UltraCold Electron Source

In a magneto-optical trap (MOT) rubidium atoms are laser-cooled down to almost absolute zero temperature. These atoms are then carefully ionized in two steps (excitation and ionization), which produces an ultracold electron bunch (green). This electron bunch is then accelerated towards the sample. Design: J. Franssen and E. Rietman Artwork: D. Nijhof

First 2D protein crystals

This image, taken with a Transmission Electron Microscope, shows 2-dimensional crystals of bacteriorhodopsin (or 鈥榩urple membrane鈥�). These are sheets consisting of a single layer of proteins. They are only 5 nanometer thick, and a few micrometers across. These crystals will be the first test sample for our molecular movie.

A diffraction pattern from a 2D protein crystal

This image was taken with the Transmission Electron Microscope in 鈥榙iffraction mode鈥�. It shows that the sample (purple membrane) is crystalline, with a lattice spacing of around 5 nm, which is what you would expect for this protein. This is raw data from a first measurement, and there is still a lot to be improved.

Our Partners

Researchers involved in this project

Subsidy Provider

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    EUC

    Julius Huijts is supported by a MSCA Fellowship of the European Union.

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    Branco Weiss Fellowship

    Julius Huijts is supported by the Branco Weiss Fellowship - Society in Science, administered by the ETH Z眉rich.

RECOGNITION

Join our team!

You are welcome to do your bachelor- or masterproject within our team! If you are interested, please get in touch with Julius Huijts or Jom Luiten.