It is common knowledge that an ethernet connection is safer than a wireless connection, and cellular organelles share this approach. To communicate directly among each other, organelles are thought to use Membrane Contact Sites (MCS), the “optical fibers” at the intracellular level. Organelles are in a prime position to sense and communicate stress signals due to their tight integration into the cell’s metabolic networks. Inter-organelle communication is thus crucial to pass on the message to coordinate cellular stress responses and maintain homeostasis. I hypothesise that MCS allow fast and efficient communication of stress signals between intracellular organelles (e.g. mitochondria and ER) to coordinate the cellular stress responses. However, the organelle tethering proteins, the stimuli driving MCS formation and the signalling molecules mediated through these MCS remain elusive in plants. In INTERCOM, I will characterise ER-mitochondria communication in response to stress in Arabidopsis thaliana. For that, I will leverage the host lab’s previously established ER-mitochondria communication model system and establish a proteomic screening setup to identify novel proteins involved in ER-mitochondria MCS in plants. In addition, I will develop a high-throughput platform to study inter-organelle interactions in vivo and to identify stimuli driving MCS dynamics. Finally, I will employ genetically encoded biosensors to pinpoint ROS and calcium inter-organelle signalling events. To reach my goal, I will combine my expertise in intracellular signalling and bioimaging with cutting-edge interactomics, live-cell imaging and high-content technologies available at the host institute. This innovative and interdisciplinary approach will allow me to shed light on plant inter-organelle communication, a field still in its infancy in plant biology with the potential to pave the path for the biotechnological engineering of plants more resilient to harmful environmental conditions.