This paper presents an empirically grounded case-based analysis of quadruple helix innovation networks. On the basis of qualitative interviews with representatives of 16 heterogeneous networks, we investigate the functional network roles of 172 actors from the fields of academic research, business, government and society. In this article we focus on universities and research and technology organisations, which face the challenge of having to redefine their functional roles and unique value in the face of increased diversification of knowledge sources within current quadruple helix innovation systems. We delineate both existing and potential future roles for academic actors using a typology of functional roles, and present the challenges research establishments must meet in order to fulfil these roles successfully. Finally, we outline the implications of this analysis for the strategic positioning of research institutions, so as to ensure the future inclusion of their innovative capacity in collaborative innovation networks.