This paper describes how design research has been deployed to stimulate and facilitate two cross-sector collaborations between industry and academia. Two research projects conducted by the School of Design at the Royal College of Art illustrate how the engagement of more than 200 cross-sector experts fostered the development of a design led strategy to prevent and mitigate future global risks through a new culture of safety. This is a strategy designed upon the synergies of collaboration that value people and their resilient capability of bouncing back through adaptation and creativity. These research projects evidence the need for creative methods that use culture, knowledge and experience as assets to construct a human-centred safety approach. With the ambition to rethink how humanity reconciles the fundamental nature of machines (reliable repetitious function) and people (divergent variable behaviours) these two projects find that people and their behaviour can be the driving intelligence capable of tackling complex future, global, challenges in dynamic situations.