Researchers develop 3D protein models
Researchers have developed new microscopic techniques capable of achieving accurate 3D protein models which could lead to new cancer therapies and treatments for diseases such as Alzheimer’s.
The EM-FRAME project has pioneered the use of new electron detectors to observe increasingly smaller particles, created ‘3D movies’ of proteins to offer sharper images, and developed techniques to create 3D images of proteins in different configurations.
The project was funded by a Marie Skłodowska-Curie Actions grant, which allowed project co-ordinator Sjors Scheres from the Medical Research Council’s Laboratory of Molecular Biology, UK, to bring Xiaochen Bai, a post-doc researcher from China, into his lab.
Scheres said: “We became a two-way team; Xiaochen would work on the electron microscope while I would work on the software.”
The scientists began by freezing slides of super-thin layers of water, which protected the protein molecules inside and enabled them to take a number of 2D images in an electron microscope. When fed into a computer, these 2D images could be turned into stable and clear 3D images of the protein.
Scheres said: “In addition, we trialled new digital chips for photographing proteins – like the chips you might find in an iPhone – which proved more efficient in detecting electrons than traditional film.”
The project has also opened the door to the development of complete 3D computer models of proteins carrying out specific functions.
Scheres added: “Gamma-secretase, one of the proteins in the membrane of cells that we have studied, for example, plays a key role in controlling signalling pathways, and its malfunction has been linked to cancer.
“Also, improper functioning of this protein can lead to aggregation of amyloid beta peptides, which have been found in large amounts in the brains of Alzheimer’s patients.”
Scheres has since trialled the techniques pioneered through the EM-FRAME project to observe the ribosomes of the parasites that cause malaria.
