CDB Seminar - Rebecca Taylor, University of East Anglia

Talk extract: To adapt and survive, organisms must be able to detect and respond to environmental changes. In animals, this is mediated by the sensory nervous system, which activates defensive responses upon identification of hazards, such as reduced oxygen availability, temperature increase or food shortage. In addition, the detection of stress within cells activates cellular stress responses, such as the unfolded protein response of the endoplasmic reticulum (UPRER), which respond to homeostatic imbalance by activating mechanisms that restore homeostasis. As animals age, they lose this ability to recognize and respond to stress, resulting in increased mortality and age-related disease. In particular, reduced activity of the IRE-1/XBP-1 signaling branch of the UPRER has been linked to brain aging and neurodegeneration, whereas genetic activation of XBP-1 can protect animals against proteotoxic insults. Recent evidence suggests that neurons can trigger the cell non-autonomous activation of cellular stress responses in peripheral tissues, leading to coordinated increases in organismal resilience and lifespan. My lab is interested in elucidating the connection between neuronal perception of environmental stress, the activation of the UPRER in downstream tissues via neuronal signalling, and improved lifespan and healthspan. In doing so, we aim to uncover molecular targets through which to promote resilience and healthy ageing.

Suggested references:

• Taylor, R. C. & Dillin, A. XBP-1 is a cell-nonautonomous regulator of stress resistance and longevity. Cell 153, 1435–1447 (2013).
• Imanikia, S., Özbey, N. P., Krueger, C., Casanueva, M. O. & Taylor, R. C. Neuronal XBP-1 activates intestinal lysosomes to improve proteostasis in C. elegans. Curr. Biol. 29, 2322–2338 (2019).
• Imanikia, S., Sheng, M , Castro, C., Griffin, J.L., Taylor, R.C. XBP-1 Remodels Lipid Metabolism to Extend Longevity. Cell Reports 28, 581-589 (2019).
• Özbey, N. P. et al. Tyramine acts downstream of neuronal XBP-1s to coordinate inter-tissue UPRER activation and behavior in C. elegans. Dev. Cell 55, 754–770 (2020).
• De-Souza, E.A., Thompson, M.A., Taylor, R.C. Olfactory chemosensation extends lifespan through TGF-β signaling and UPR activation. Nature Aging, 938–947 (2023).

Host: Arantza Barrios