Professor Knowles undertook his preclinical training at Cambridge University and then moved to the London Hospital Medical College, qualifying in 1992. Prior to specialist training, he undertook research based at Barts & the London and, funded by the Royal College of Surgeons of England, leading to the degree of PhD at the University of London in 2000.
He entered the Specialist Register in 2005 as a general and colorectal surgeon. In 2006, he was appointed Senior Lecturer in Colorectal Surgery on the basis of a prestigious award from HEFCE. He holds an Honorary Consultant appointment at Barts Health NHS Trust.
Professor Knowles is a Fellow of the Royal College of Surgeons of England, Co-director of the National Centre for Bowel Research and Surgical Innovation, Chairman of the Whitechapel Society for Gastroenterological Research, Research lead of the Neurogastroenterology Section of the British Society of Gastroenterology, Deputy Clinical Director of the NHS Bowel Healthcare Technology Cooperative and Chair of the GI neuromuscular pathology international working group.