Background
I am professor of molecular biology and principal investigator of the research group. I have a BSc in Biochemistry and a PhD in protein crystallography. I have previously worked with the Richardson group at Duke Univerisity and the Blundell group in Cambridge.
Cambridge Structural Biology group
Research Interests
Sequence-structure relationships
Protein structure is determined by the linear sequence of amino acids. This amino acid chain rapidly folds up in the cell, giving rise to complex three- dimensional structures. For most proteins it is this three dimensional structure which determines how proteins function in the cell. Unfortunately, we do not know the details of why proteins fold as they do, nor how the sequence determines the structure. I hope to gain insights into thes e relationships by analysis of protein structures, and the development of physics-based rules that can be used to predict protein structure.
Evolution
Protein structure is generally more conserved than sequence, because of the intimate relationship between structure and function. The maintenance of function is strongly selected for evolutionarily, and so this place restraints on protein structure. Just as the sequence of a protein gives rise to the structure, the structure places evolutionary restraints on the sequence. By understanding these restraints we can understand how structure evolves over time, how one structure can give rise to another, and we can predict structure using evolutionary information.
Protein-protein interactions
The majority of proteins function by making interactions with other proteins. The whole set of these interactions can form a complex network of interactions that underpins biological function. We aim to determine how specific proteins recognise each other, how these specificities evolve, and how functions can emerge from the whole network.
How function arises from complex systems
The cell doesn't care how functions are carried out, and natural selection is blind to mechanisms, so long as they work efficiently. The result is that many molecuar functions work through a combination of differnt types of molecules interacting in a range of ways. Only by embracing all of this complexity (and integrating data of a wide range of types) can we understand how function, and so life, emerges.
Evolutionary systems biology
Since function arises from complex systems, if we are to understand the evolution of function, we must understand the evolution of systems. We combine our knowledge of integrated systems with our tools for understanding processes like gene duplication and spcificity change, with the view to producing a complete model of evolutionary systems biology.