Upon completing postgraduate work at the Medical Research Council’s Clinical Research Centre in Harrow, Simon “emigrated” to the USA to take up a postdoctoral position at New York University School of Medicine, and then at Yale University as a Howard Hughes Fellow in the Immunobiology Group at Yale University. While at Yale he gained an interest in gamma-delta (γδ) T cells working closely with Adrian Hayday on molecular genetics and then with Professor Peter Doherty to establish their role in (viral) infectious disease.

After Yale Simon took up a faculty position at the University of Pennsylvania in Philadelphia where he developed a research interest in mucosal and GI-tract immunology, performing studies in germfree mice with Professor John Cebra that helped establish the role of gut microbes in the aetiology of inflammatory bowel disease (IBD).

After 15 years in the USA, he returned to the UK to take up the Chair in Molecular Immunology at the University of Leeds where he established a new research programme on commensal gut bacteria and Bacteroides genetics leading to the development of a Bacteroides drug delivery platform that is being used for developing new interventions for IBD and for mucosal vaccination.

In 2008 he was recruited by UEA and IFR to develop a gut research programme, taking up the Chair of Mucosal Immunology at UEA-MED and the position of Head of the Gut Biology Research Programme at IFR, which later became part of the Gut Health and Food Safety (GHFS) Programme. GHFS research covers a broad area of gut biology including epithelial cell physiology, mucus and glycobiology, mucosal immunology, commensal microbiology, foodborne bacterial pathogens, and mathematical modelling and bioinformatics. The success of this programme has led to the establishment of the Gut Microbes and Health research programme that is integral to the research agenda of The Quadram Institute.