The Oxford Science Lecture Series

Professor E. Yvonne Jones FMedSci

Cancer Research UK

"Postcards from the surface: The Structural Biology of Cell-Cell Communication"

Dorothy Hodgkin Memorial Lecture 2008

University Museum, Oxford, 4th March 2008

Yvonne Jones is Director of the Cancer Research UK Receptor Structure Research Group which is primarily focused on the structural biology of extracellular recognition and signalling complexes. The major technique they use is that of protein crystallography, pioneered in Oxford by Dorothy Hodgkin. Professor Jones studied Physics at Oxford and spent many years in the Laboratory of Molecular Biophysics before moving to work with Cancer Research UK at the Wellcome Trust Centre for Human Genetics.

She began her lecture with movies showing neutrophils and macrophages, cells which act as the body’s defenders by clearing out unwanted cells and debris, sensing the presence of invading bacteria. She then showed a painting by David Goodsell of the Scripps Institute showing molecules on the surfaces of a macrophage and a bacterium “talking” to each other. To see actual molecules in this detail, Professor Jones uses x-ray crystallography. She described how it is necessary to obtain very pure crystals of the protein, as the repetition of the molecules lined up in identical orientation within the crystal acts to amplify the x-ray signals, and how the synchrotron at the Rutherford Appleton Laboratories enables them to study very small crystals. Although they now use fast computers to interpret data, the basic processing is the same as that used by Dorothy Hodgkin when she first demonstrated that it was possible to keep proteins stable under x-rays. However where it took Dorothy 90 hours to obtain a diffraction pattern, modern techniques obtain the same results in 10 seconds!

Professor Jones went on to describe some of her work studying the molecules on the surface of T cells, which play an important and integral role in the body's defenses. She showed a movie of a T-cell killing an infected cell and explained that T-cells are very effective killing machines and so they have to be sure that they have found the right target before destroying it. They have receptors on their cell surface which recognize shapes on the surface of other cells. If the receptors recognize the shape of a normal protein then the cell is ignored, but if the receptors find a structure they don’t recognize then they tell the T-cell to destroy that cell. Professor Jones also studies cell adhesion molecules involved in the balance between cell mobility and adhesion. She described how she has established that these molecules have a rigid structure which is conserved in species as diverse as frogs and man. When these rigid molecules from different cells encounter each other, they “lock arms” and cause their host cells to be held apart at the ideal distance for adhesion to occur.

Professor Jones concluded her lecture with a couple of photographs she had taken at a conference in Beijing in 1993 showing Dorothy Hodgkin surrounded by friends and colleagues and epitomizing the strong friendships Dorothy had made around the world.

Dr Carolyn Carr, Cardiac Metabolism Research Group, University of Oxford.