Abstract

Detecting and responding to environmental stress is crucial to the survival of organisms. My lab studies the ways in which stress detection by the nervous system leads to the activation of organism-wide defence mechanisms that can slow down the ageing process. In particular, we are interested in the unfolded protein response of the endoplasmic reticulum (UPRER), and its activation in downstream tissues following signalling by neurons. Through studying the transcriptome of different cell types in C. elegans following genetic activation of the UPRER , we have uncovered mechanisms by which UPRER activation in the nervous system triggers the sending of UPRER -activating signals to the intestinal cells of the animal, and have also revealed the ability of neuronal stress response activation to alter the behavior of the worm in ways that are appropriate to stressful environments. In addition, we have identified a novel ability of intestinal UPRER activation to enhance the acidity and activity of lysosomes, leading to improved protein and metabolic homeostasis and resulting in delayed ageing and extended longevity. Finally, we have pinpointed specific environmental cues that trigger UPRER -activating neuronal signalling. Our analyses have therefore revealed novel mechanisms by which multicellular organisms orchestrate resilience in the face of stress, utilizing neuronal signaling systems to coordinate multiple responses across different tissues of the animal.