Established process models for knowledge discovery see the domain expert in a customer-like, supervising role. In the field of bio-medical research, it is necessary for the domain experts to move into the center of this process with far-reaching consequences for their research work but also for the process itself. We revise the established process models for knowledge discovery and propose a new process model for domain-expert driven knowledge discovery. Furthermore, we present a research infrastructure which is adapted to this new process model and show how the domain expert can be deeply integrated even into the highly complex data mining and machine learning tasks.