13 April

Thesis defence Angelica Aguilera Gomez

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Today Angelica Aguilera Gomez from the Rabouille group will defend her PhD thesis, entitled “survival lessons from stress assemblies.”

In her thesis Aguilera Gomez studied the stress response to amino-acid starvation using Drosophila S2 cells. Amino-acids are the protein building blocks, and starvation occurs when they are not available in the medium. She noticed that this starvation resulted in major changes of the cellular architecture. First, there was a dramatic remodeling of the ERES, which is the exit site of the endoplasmic reticulum (part of the secretory pathway), and the ERES components are reshaped into novel non-membrane bound cytoplasmic stress assemblies with liquid droplets properties, called the ‘Sec body’. Amino-acid starvation also leads to the simultaneous formation of another stress assembly, the ‘stress granule’ and she has found that their formation is coordinated via the major ERES component Sec16. Sec bodies depends on the direct modification of Sec16 by PARP16, and stress granules depends on Sec16 binding to, and stabilizing the RNA binding protein Rasputin.

A big question is whether these stress assemblies are good or noxious. On one hand, Sec bodies preserve of ERES components and ensures that the secretory pathway can resume its function once the stress is relieved so that cell growth and proliferation continues. This is also the case for stress granules. However, stress assemblies can become dysfunctional as they become irreversible and therefore toxic for the cell, leading to pathologies such as many neurodegenerative diseases including ALS.

Taken together, Aguilera Gomez has unraveled novel mechanisms required for the formation of stress assemblies upon amino-acid starvation. She has unveiled similarities but also critical differences in the formation of these assemblies depending of their content and the given stress.