This chapter aims to explore the organisation and reorganisation of knowledge and ‘spaces of knowledge’, and the interaction and tension of different institutions and actors in shaping and distinguishing different forms of knowledge and knowledge production. It analyses some aspects of the complex reorganisation of the city as a consequence of the establishment of the university there in 1537. The chapter also aims to analyse the different sources related to the personal trajectory and career of Andre de Avelar, professor of the chair of mathematics at the University of Coimbra, who was brought before the Inquisition accused of practising Judaism in 1620 and again in 1621. It considers the configuration and reconfiguration of urban spaces and the social milieu that are crucial to a better understanding of the development of knowledge as a social and historical process, deeply rooted in the political, cultural and institutional dynamics.