The recovery of renewable energy or production of bio-chemicals from waste streams is a key aspect of the sustainable bio-economy. Large volumes of wastewater are generated by bio-refineries, which require adequate valorisation. Anaerobic microbial technologies that rely on the ability of micro-organisms to grow in spherical granules have been used for decades to treat such waste streams, yet, the main mechanisms that underline anaerobic granulation remain unclear. The aim of this research project is to unravel the key physical, chemical and/or microbiological factors that determine granulation to better steer anaerobic granular processes. First, the factors that determine microbial co-aggregation between different partners that can metabolically benefit from each other will be investigated, which will be linked to the impact of environmental conditions and the importance of interspecies communication. Next, synthetic granules will be constructed, based on a novel approach to investigate microbial and ecological aspects, such as the importance of 3-dimensional organisation, the specificity of the interaction and the potential contribution of conductive elements. Finally, the long-term stability and performance of tailored synthetic granules will be compared with their “natural” counterparts in terms of resistance to disturbances and invasion. The knowledge generated here will allow to move beyond the current limits of anaerobic technologies towards novel applications.