Many of the world’s most precious artworks are made of stone and their irreversible disappearing due to biological attack is a worldwide concern. Cyanobacteria colonize outdoor surfaces and develop biofilms, which, in turn, causes aesthetic, chemical and physical decay. The fragile character of the stone heritage material is further exacerbated by the unpredictable nature of environmental changes impacts, posing challenges for conservation management. Although there have been EU projects and scientific papers on cyanobacteria, the role and behavior of these microorganisms within the biofilm matrix and their complex interactions with the external environment is still unknown. ESENCYA provides an innovative, interdisciplinary and multidisciplinary research to investigate perception of environmental changing in cyanobacteria within the biofilm matrix for sorting out time-spatial relationships and to elucidate microorganism-matrix, inter-organism, biofilm-atmosphere and biofilm-stone interactions.The project spans sophisticated microscopic techniques, biofilm matrix and gene expression analysis, damage assessment and data modeling techniques in world leading research institutions in microbial biofilm in USA and in cultural heritage microbiology in Italy. The research will be approached from two complementary angles: i) Lab-scale study to examine the sensory machinery of cyanobacterial biofilms by analyzing the cell’s capacity to sense different chemical and physical properties of the biofilm matrix, to integrate the incoming signals and to respond to them, triggering specific biodecay activities; ii) real heritage case studies to investigate the ecological landscape of cyanobacteria within subaerial biofilms.The outcomes will generate valuable new knowledge to model and predict surface biodeterioration in the face of environmental changes. This project represents an opportunity for Europe to keep its world leadership in research and conservation of cultural heritage.