The cryo-electron microscopy: a structural biology revolution.

We have now access to this information, for the very first time in the history of science. It gives us access to the conformational dynamics of some objects which were not easy to have access to before. In order to conduct research in structural biology, we benefit from advanced technology platforms such as electron microscopy, « NMR » but also high-performance beam lines at the ESRF. They are used to solve structures using crystallography. IBS’s research is conducted by 19 research groups.

Their work is organized around 3 research programs: the first approach focuses on infections, microbiology and the immune system ; the second one deals with dynamics, assembly and reactivity ; the third one looks at membrane proteins and glycobiology. My work focuses on the understanding of bacterial cell wall perforation by bacteriophages, viruses which infect bacteria. Bacteriophages are a few hundred nanometers long. Electron microscopy is thus the preferred technology to study these objects which are big but not huge. It produces beautiful cryo-electron microscopy images. It give us not only the opportunity to observe the architecture of the phage but it also allows us to obtain atomic-level resolution of the different proteins and to understand how they can perforate the bacterial cell wall. The interesting thing about this project is the collaboration of specialists from the 3 complementary techniques: crystallography, NMR and electron microscopy.

Here at the IBS, we study serotonin receptors which are key actors of the information transmission inside the brain and which are located at synapses. Electron microscopy allows us to capture not only one but a whole group of images of the conformation of this protein throughout its cycle of action: when it is resting, when serotonin is approaching and when serotonin enables the creation of a hole in the membrane large enough for ions to pass. This is the role of this receptor. This gives us a much broader and complete view of the molecular mechanism of serotonin receptors. The IBS owns a Thermo Scientific™ Glacios™ Cryo Transmission Electron Microscope. It allows us to load simultaneously up to 12 grids inside the microscope. It is equipped with 2 electron counting direct detection cameras, Falcon 2 and K2, that record high-resolution movies. Our current resolution record for this equipment is 2.8 ångström.

This microscope is mainly dedicated to high-resolution single particles studies but it is also equipped to do electron tomography on non-regular objects. It is possible to come directly with liquid samples as we own a « Vitrobot » for the vitrification of sample by plunge-freezing. Or you can also come with frozen grids which will be observed in the microscope here. These samples can be isolated proteins, protein complexes or virus. There is only one restriction: samples can’t be infectious. The microscope has also an automatic data collection software, named EPU, which allows to record 800 images per day..

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