1988-1992
BSc University of Bath

1992-1995
PhD University of Bristol

1995-1996
Lecturer, University of Bath

1996-2001
Postdoctoral Research Associate, Duke University, North Carolina, USA

2001-2003
Research Fellow, University of Cambridge

2003-2007
Lecturer, University of Manchester

2007-2012

Senior Lecturer, University of Manchester

2012-present

Professor, University of Manchester

Protein Structure

I am interested in understanding the three-dimensional structure of proteins. This breaks down into three main research areas. All of these areas are investigated using computational methods.

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 these 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 structure. 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 function

The strongest evolutionary restraints on a protein are in the functional sites, for example the active site of an enzyme. We can use our knowledge of protein structure and the evolutionary restraints on it to identify functional sites, binding sites, oligomerisation sites and protein-protein interaction sites. We would like to be able to use this information to identify protein function directly. This is particularly important at the moment, given the wealth of sequence data from the various genome-sequencing projects and the structural data from structural genomics projects. This data must be turned into usable biological information if most use id to be made of it.