The Cytoplasmic Heat Shock Response in Health and Disease

The cytosol of the cell has its own dedicated stress response to regulate protein homeostasis, known as the heat shock response (HSR). As organisms age, the HSR declines in function, suggesting that this decline may be responsible for accumulation of protein damage and toxicity. Previous work from our lab has demonstrated that the nervous system has a unique ability to coordinate the HSR across tissues, and that the main effector of this response, HSF-1, feeds into diverse signaling pathways to help rescue cellular health under stress (1-2). Our current work focuses on elucidating mechanisms of protection by cell-cell communication of the HSR and examining tissue-specificity of this response. Further, we are interested in how HSR activation can ameliorate cytosolic protein misfolding disease phenotypes.

 

(1) Baird NA, Douglas P, et al.

HSF-1-mediated cytoskeletal integrity determines thermotolerance and life span.

Science. 2014.   PMID 25324391

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(2) Douglas, P, Baird NA, et al.

Heterotypic Signals from Neural HSF-1 Separate Thermotolerance from Longevity. 

Cell Reports 2015.   PMID 26257177