ABSTRACT Through editorials such as Bob Root-Bernstein’s ArtScience “manifesto” in Leonardo Vol. 44, No. 3 (2011), Leonardo has long encouraged a broader and more inclusive understanding of the subtle interplay between science and art, and the belief that as individuals and cultural agents we all blend both aspects in our respective fields of endeavor. However, discourse and collaboration across the arts, sciences and humanities is not yet a mature and fully effective process. The authors contribute to this debate by drawing on elements of their Project Dialogue research program, set alongside published accounts of experiences at earlier U.K. art-science programs, to sketch out a theoretical framework that could inform ArtScience through a re-formulated cultural model of knowledge encompassing art and science.