Dissecting neuronal regulatory pathways of the cellular heat shock response to elevated temperatures and misfolded proteins

• Applicant: Dr. Carmen Krammer
• Subject Area: Cell Biology
• Term: from 2009 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 120237058

The heat shock response is an important cytoprotective mechanism to counteract the harmful effects of accumulated non-native proteins and is induced by a number of stressors. At the cellular level, it is triggered by the depletion of chaperones that are recruited to misfolded proteins. Several recent studies suggest that metazoans have an additional non-cell autonomous neuronal regulation of the heat shock response to integrate and coordinate the organismal response to stress. The laboratory of Dr. R. Morimoto demonstrated that the heat shock response in Caenorhabditis elegans is regulated by the thermosensory neurons AFD by a yet unidentified mechanism. This proposal aims to elucidate neuroendocrine pathways that regulate the expression of heat shock proteins in multicellular organisms upon elevated temperatures and expression of aggregation-prone proteins. The involvement of neuronal signaling in non-cell autonomous regulation of the heat shock response will be analyzed employing a genetic approach to identify the downstream molecules that regulate the somatic heat shock response. Furthermore, novel C. elegans transgenic model systems will be established to analyze if and how a heat shock response due to an imbalance in protein homeostasis is regulated by neuronal subsets. By studying the role of neuronal signaling pathways on chaperone expression and protein folding in different tissues, these studies will provide important insights into general mechanisms of a neuronal control of the stress response and protein homeostasis.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Richard I. Morimoto