Structural biologist Dale Wigley talks about his fascination with the beauty of biological molecules and the buzz of being the first to discover them.
Dale recently joined Imperial from Cancer Research UK to form part of the new Structural Biology Section within the Department of Medicine, alongside Professors Paul Freemont and Xiaodong Zhang. Its goal is to integrate cutting edge technologies and disciplines to unravel fundamental molecular mechanisms behind pressing human disease with a view to establishing new potential molecular targets for drug therapy.
What’s it like being back in the higher education environment?
Moving from a research institute with a focus on cancer to a multidisciplinary University environment will allow me to broaden my research interests. The opportunity afforded by the creation of the Section of Structural Biology within Medicine at Imperial should promote synergistic interactions between experts in molecular aspects of diseases and structural biologists, leading to advances in our understanding of diseases and using this knowledge for drug discovery - an opportunity that I find very exciting.
Have you always been captured by the exquisite structures found in biology?
For me, seeing is believing. Structural biology allows us to visualise molecules to understand the chemistry of their action. I get a buzz from knowing that when we determine the molecular structure of a protein we can be sure that we are the first human beings to ever see that detail and the insight that brings.
Watson, Crick and Wilkins elucidated the structure of DNA over 60 years ago - are we still unravelling this mighty molecule?
At that time they had no idea of the molecular complexity and number of proteins required by the processes that replicate and repair DNA. In fact, even today we are still discovering new protein players in these processes in bacteria, never mind humans ! The DNA in a human cell contains about a 2m length of DNA. That’s an awfully large amount of information to replicate each time the cell divides and to keep in good shape against a battery of chemical and mechanical damage. Consequently, it takes a lot of proteins to perform this task accurately.
What are you most excited about with regards to the new phase of your research work here?
When I first began my research group in Oxford in the early 1990s, I was working on bacterial DNA replication and repair as a target for novel antibiotic discovery. In subsequent years I got involved in these processes to understand their role in cancer. Moving to Imperial has allowed me to return to antibiotic development − which has become an even more significant medical issue in the intervening years (see centre pages).
I notice you are also part of Imperial’s Antimicrobial Research Collaborative?
Yes, I believe Structural Biology has an essential role to play in the discovery and development of new antibacterials and developing ways to overcome resistance to existing antibiotics. At the end of the day, these are all molecular processes so we need to understand them at that level of detail. Structural biologists have the ability to provide this information to be used by biochemists, biologists and chemists to develop new drugs to meet this challenge.
