New work from Dr. Karl Kadler's lab utilized CHPs to see how BiP influences the circadian rhythm of cells. They saw that BiP overexpression resulted in a more robust circadian rhythm but that it led to retention of procollagen in the ER as non-helical collagen and reduced the assembly of collagen fibers. They were able to visualize this by using F-CHPs. Great work and interesting findings!

Abstract: ER stress and dysregulation of collagen synthesis are associated with progression of disease in cancer and fibrosis. Collagen synthesis is co-ordinated by the circadian clock,and in cancer cells, ER stress induces a phase shift in circadian oscillations. We hypothesised that an interplay exists between circadian rhythm, collagen synthesis and ER stress in normal cells. Here we show that fibroblasts with ER stress cannot respond to circadian cues. Conversely, overexpression of BiP or treatment with chemical chaperones strengthen circadian rhythms. The significance of these findings was explored in tendon.We showed that BiP expression is ramped pre-emptively prior to a surge in collagen synthesis at night, thereby preventing protein misfolding and ER stress. In turn, we propose, this forestalls activation of the unfolded protein response in order for circadian rhythms to be maintained. Thus, targeting ER stress could be used to modulate circadian rhythm and restore collagen homeostasis in disease.

Check out the full article FULL ARTICLE HERE

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