We use a range of sophisticated techniques to investigate the structure and function of the biological molecules that make up all living things.
We study proteins and protein complexes. Proteins are composed of linear sequences of basic biological building blocks called amino acids (of which there are 20 naturally occurring). Different protein sequences give rise to very different three-dimensional shapes and functions of the proteins. Protein complexes are formed of several proteins. Moreover, proteins, or proteins complexes, can be bound to other macromolecules like DNA, RNA or carbohydrates.
Our work helps scientists at the Crick to understand the shape and mechanical properties of proteins and their complexes, providing valuable insight into their function. For example, we can see how the shape of viruses allows them to infect cells by ‘slotting’ into a particular part of the cell surface. Such knowledge helps scientists to develop new ways of tackling diseases, for example by blocking the viral entry points or identifying weak points that can be targeted by drugs.
We use a variety of specialist techniques to determine the structure of proteins, including X-ray crystallography and electron cryomicroscopy (CryoEM).
X-ray crystallography involves purifying proteins and getting them to form crystals, which we can then study using state-of-the-art X-ray diffraction equipment. This involves exposing the protein crystals to high-intensity X-rays and detect how the atoms in the protein diffract the X-rays. With the information provided by the diffraction pattern we can work out the three-dimensional atomic structure of the protein in the crystals.
For proteins that don’t form large crystals, we use CryoEM, a revolutionary new technique that was awarded the 2017 Nobel Prize in Chemistry. CryoEM involves firing electrons at proteins that have been frozen in solution and then measuring the scattered electrons that emerge at the other side.