[
International Worm Meeting,
2021]
Starvation of C. elegans upon hatching causes developmental arrest. Arrested animals can survive for more than to 2 weeks in the absence of food and restart growth when nutrition improves. However, upon re-feeding animals resume growth with a delay that increases proportionally with the duration of starvation. Survival during starvation requires autophagy, and the starvation response is under tight control by metabolic signaling. For example, we found that mutants with constitutively active mTOR signaling die within 1 week of starvation. The goal of this project is to characterize the dynamics of proteome turnover during starvation and during recovery, and to ask if specific proteins are preferentially degraded during starvation to maintain survival. We hypothesize that under extended periods of starvation proteins needed for growth and biosynthesis, such as ribosomes and mitochondria, are preferentially turned over, as compared to structural proteins that are essential for survival, such as collagens or histones. Resuming growth upon feeding would consequently require re-synthesis of the biosynthesis proteins, and thereby delay onset of growth in proportion to the duration of starvation. To test this hypothesis, we established an assay for protein quantification based on HiBit technology. HiBit relies on a split luciferase and allows for detection of specific proteins at high accuracy and sensitivity in a microplate-based readout. Using this assay, we find that indeed ribosomal proteins declined continuously during L1 arrest. We will now test if this decline relies on autophagy, and if the turnover rate of ribosomes can explain how survival is affected in mutants with perturbed autophagy and growth signalling. Finally, we will use proteomics to assess how the proteome composition globally changes during L1 arrest on a time scale of weeks.