"Understanding the role of autophagy in the control of RNA trafficking, triage and translation"

In times of stress, cells re-prioritize their gene expression programs and metabolic pathways in order to limit damage and survive until the stress is resolved. These cellular stress responses are complex and poorly understood, but accumulating evidence indicates that they play important roles in limiting the damage of infection, and monitoring aberrant cellular behaviour that might lead to cancer. One example of such a cellular stress response is autophagy, which literally means 'self-eating'. Autophagy is an evolutionarily conserved process that permits cells to survive the stress of starvation by promoting the degradation and recycling of a variety of cellular structures, thereby providing essential cellular building blocks and energy for survival. Interestingly, stress has also been shown to impact gene expression by influencing global messenger RNA (mRNA) turnover and translation. A central feature of the stress response is rapid and reversible inhibition of translation, which prevents the accumulation of aberrant proteins and facilitates the production of key stress response proteins. Translationally inactive mRNA-protein complexes nucleate the formation of large cytoplasmic aggregates known as stress granules (SGs). SGs play a central role in controlling the translation machinery during stress, serving as sites where translationally-inactive transcripts are triaged and routed to sites of re-initiation or degradation (e.g. processing-bodies). Despite their important and perhaps complementary roles in controlling gene expression and maintaining cellular homeostasis, the relationship between autophagy and SGs/p-bodies has not been explored to date. The current proposal is aimed at elucidating the relationship between these complex homeostatic mechanisms, using a suite of molecular tools and high-resolution imaging techniques. This work will provide new insights into the fundamental cellular processes that control gene expression during times of stress.