£2.34million Wellcome grant for cryo-electron microscopy
Equipment will enable scientists to learn more about the structures and mechanisms of molecules
Image: A ring-shaped protein complex which threads unfolded proteins through a central channel, seen from the top. This structure was determined by cryo-electron microscopy, using the same type of advanced electron microscope that has now been funded at Birkbeck.
A team of scientists at Birkbeck and the Institute for Structural and Molecular Biology (ISMB) has been awarded £2.34 million by Wellcome, to enable them to buy a state-of-the-art cryo-electron microscope for molecular and cellular biology.
The Birkbeck/ISMB team use electron microscopy to obtain images of the molecules and cells that form the machinery of life. When electrons are focused on tiny samples, they act as waves with a wavelength that is much smaller than that of visible light, enabling scientists to see the microscopic world in great detail, nearly to the level of atoms. Since it was invented in the 1930s, electron microscopy has steadily improved in power and sophistication, and recent advances have moved this method to the forefront of structural biology. Understanding the structures of biological molecules and assemblies reveals their mechanisms of action and makes it possible to design drugs or treatments for diseases.
The research projects that will be done on the new microscope are mainly focused on the microscopic machines within living cells that carry out functions such as protein synthesis, protein folding, unfolding and reversal of protein aggregation. These are important in maintaining health and protecting most of us against neurodegenerative diseases, such as Alzheimer’s, for most of our lifetime. Other molecular machines being studied by the Birkbeck/ISMB group function as membrane hole-punchers that are used in warfare between pathogens and the host immune system, and structures used by bacterial pathogens to attach to their host cells and for bacterial multiplication. Other machines that the group studies include those for the assembly, replication and transmission of viruses, as well as cellular motors and intracellular transport systems in cell division and gene transcription. An essential part of this work is computational analysis to interpret the electron microscopy structures.
Helen Saibil, Bernal Professor of Structural Biology, said: “The advances in the power and sophistication of the new microscope are very exciting, but they have come with a very high cost, and the best available microscopes have become too expensive for most university laboratories to buy. We are delighted that Wellcome has made this equipment award that enables us to acquire the best available microscope for our work.”
The microscope will be housed in the basement of the Birkbeck main (extension) building, adjacent to the existing four microscopes, which are used for training and project development, and the associated sample preparation facilities.
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- Image information: The central channel is partly filled by a protein being threaded through (dark purple region near the centre of the complex). The electron density map is shown as a semi-transparent grey surface, and the protein subunits are shown in rainbow colours. The elongated bright purple densities are the positions of bound nucleotides, the energy fuel that drives the protein machinery to unfold and thread the protein chain. The work was done by Celia Deville in the Saibil group, along with a former group member, Marta Carroni, who is now at SciLife Lab, University of Stockholm, and was in collaboration with the team of Bernd Bukau and Axel Mogk at the Centre for Cell and Molecular Biology (ZMBH) in Heidelberg, and is published in Science Advances.