Project Details
Projekt
Role of sensory perception in cell non-autonomous proteostasis signaling
Applicant
Professor Dr. Thorsten Hoppe, Ph.D.
Subject Area
Cell Biology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 531902955
The accumulation of damaged and aggregated proteins is associated with cellular toxicity and loss of physiological integrity. Degradation of damaged proteins is mediated by the 26S proteasome upon attachment of ubiquitin proteins (ubiquitination). Despite progress in the characterization of proteolytic degradation pathways at the cellular level, cell non-autonomous mechanisms that coordinate the organism-wide activity of the ubiquitin-proteasome system (UPS) in response to environmental changes remain largely unexplored. The nematode Caenorhabditis elegans has a sophisticated chemosensory system involved in the regulation of development, mating, noxious avoidance, and food intake. Chemosensory preferences can be modified by sensory adaptation, allowing the integration of experience into behavior and physiology. We have identified changes in ubiquitin-dependent degradation rates and proteostasis upon feeding worms with different bacterial food sources. Our recent data indicate that these dietary changes in proteostasis are coordinated by a single pair of chemosensory neurons. The microRNA miR-71 functions as a regulatory node to induce cell non-autonomous coordination between olfactory neurons and intestinal cells. The central goal of the proposed research is to understand how olfactory perception and neuronal stimulation are translated into organismal adaptation of proteostasis networks. The proposed project will address brain-gut communication and systematically analyze neuronal response mechanisms induced by olfactory stimulation and proteotoxic stress conditions (Aim 1), regulation of cell non-autonomous signaling between olfactory neurons and intestinal cells (Aim 2), and tissue-specific adaptation of proteostasis pathways (Aim 3). To this end, single-cell transcriptomic/proteomic analyses, chemicalgenetic/optogenetic control of neuronal signaling, CRISPR/Cas9 gene editing, and large-scale genetic screenings will be performed.
DFG Programme
Research Units
