Preferential ribophagy balances a trade-off between starvation survival and starvation recovery in C. elegans

Part 1: Animals change their rate of biosynthesis and autophagy according to environmental factors, such as food availability. Ad libitum feeding animals benefit from rapid growth and fast reproduction, whereas starving animals halt growth and increase autophagy to utilize pre-existing proteome resources for survival. Indeed, autophagy deficient C. elegans do not recover from starvation. In this project, I want to study how animals optimally adjust proteome turnover by autophagy to maximize starvation survival. Specifically, I hypothesise that optimal resource utilization during starvation relies on preferential autophagy of proteins that are not needed during starvation, such as ribosomes. I ask whether there is preferential and selective autophagy of certain proteins in C. elegans during starvation, and whether inhibition of autophagy prevents this degradation.

Part 2: If animals improve starvation survival by recycling proteomic resources that are not needed during starvation, they may revert to the normal proteome composition before resuming development when food returns. Indeed, starved C. elegans larvae display a delay in growth onset proportional to the duration of starvation when returned to food. I hypothesise that this lag phase is due to the time it takes to reverse starvation induced proteome changes, such as replenishing ribosomes that have been recycled during starvation. I test this hypothesis by asking whether upon resuming feeding animals resume normal growth only after the replenishment of ribosomes, and whether the lag phase duration can be adjusted by titrating the level of ribosomes.

Part 3: Growth signalling controls the balance between growth and autophagy. Optimizing the level of growth and autophagy based on nutrient availability is well understood on molecular and cellular levels, but not in multicellular eukaryotes. It is not clear how specific cellular changes are beneficial on the level of an entire multicellular animal, how these changes help the animals achieve an optimal physiological response when food runs out, and how this leads to maximizing population expansion and animal fitness. I hypothesise that animals under starvation find a fitness maximising balance between biosynthesis and autophagy by controlling the level of mTOR mediated growth signalling. I ask how changing the rate of growth and autophagy by titrating nutrient sensitive mTOR activator raga-1 changes starvation survival dynamics of C. elegans.