I studied Biochemistry at University of Cambridge, followed by a PhD in Protein Design at the Department of Crystallography,‭ ‬Birkbeck College,‭ University of ‬London. Following a postdoctoral fellowship at the Protein Engineering Research Institute in Osaka under the EU scientific training program in Japan‭ I returned to Cambridge in 1990 as a Zeneca Fellow at the MRC‭‭ ‬Centre for Protein Engineering to work on protein folding, ‬classification and design. I co-founded SCOP‭ (‬the Structural Classification of Proteins database‭)‬ and developed algorithms to make protein structure predictions and assess their accuracy and to calibrate the reliability of sequence alignment methods.‭ ‬I was one of the most successful participants in the first CASP‭ (‬Critical Assessment of Structure Prediction‭) ‬competition in‭ ‬1994‭ ‬and a co-organiser of subsequent CASP competitions‭ (‬CASP2-CASP7‭) ‬until‭ ‬2007. In‭ ‬1997‭ ‬I joined the Wellcome Trust Sanger Institute to become Head of Human Genome Analysis, where I was one of the organisers of the sequencing of the human genome. In 1999 I co-founded the Ensembl project to analysis, organise and provide access to the human genome. From 2007 I led the GENCODE project to annotate the structure of all human genes, initially as part of the ENCODE project. I‭ was the Sanger Institute PI of the Genome Reference Consortium,‭ ‬which is responsible for reference genome sequences of human,‭ ‬mouse and zebrafish. I become Head of the Informatics division from‭ ‬2007. After the announcement of the 100,000 genomes project 2012 ‬I was seconded part time as specialist advisor for genomics to NHS England leading up to the creation of Genomics England. In October 2013 I was appointed Professor of Bioinformatics and Head of the Department of Medical & Molecular Genetics at King's College London and Director of Bioinformatics for King's Health Partners with a part time secondment as Head of Genome Analysis at Genomics England. In 2018 I was also appointed Associate Director (King's) for the Health Data Research UK (HDRUK) London Site.

Genomics & Bioinformatics, particularly around gene and regulatory annotation and predictive modelling; Human phenotype data, particularly around clinical data capture, organisation and research access; Genome Medicine, particularly the mainstreaming of whole genome sequencing into health systems for rare disease and cancer diagnostics, as well as enabling real time decision support for personalisation of treatment.