Measurement of proton position in DNA

Mutations are a cause of cancer and genetic disease as well as being the driver of drug-resistance in cancer and infectious disease. Watson and Crick proposed that these spontaneous mutations arise through tautomerization of DNA bases, involving the tunnelling of protons. However, despite a great deal of theororetical support for their model, experimental evidence is scanty, mosty because of difficulties in mapping proton position in the DNA double helix. This project will bring together expertise in quantum biology and chemistry available at the University of Surrey with neutron crystallographic methods at the Institut Laue-Langevin (ILL) in Grenoble. The aim of this highly innovate, cutting-edge project will be to directly determine the protonation states in each of three major forms of DNA, A, B and Z, and to model these in the context of hydration-driven stereochemical pathways that are known to occur between them. Particular attention will be focused on changes in protonation in these different forms and possible implication of tunnelling in mediating such shifts that may be a cause of mutation.

This project will involve several months work at ILL in Grenoble.