In 1999 he rejoined the Institute of Cancer Research to chair the new Section of Structural Biology (jointly with David Barford) at the Chester Beatty Laboratories in Chelsea.

In 2009 he was appointed Head of the new School of Life Sciences at the University of Sussex, relocating his laboratory to the MRC Genome Damage and Stability Centre, where he holds the position of Professor of Structural Biology.

His research focuses on understanding the structural basis for assembly, specificity and regulation of proteins and complexes involved in human diseases such as HIV/AIDS[14] and cancer.

[19] On arrival at Sussex he undertook the restructuring of the School of Life Sciences which resulted in nearly one third of the faculty accepting early retirement or leaving the university,[20] and rationalised the degree programs, stopping a number of poorly-recruiting Masters programmes.

[24] His nomination for the Royal Society reads Laurence Pearl has applied structural, biochemical and genetic techniques, to elucidate the molecular basis of function and specificity in systems of fundamental biomedical importance.