Thesis defense Chujun Zhang “Stress assemblies: Defining pathways leading to their formation and identifying their components”

All cells consist of several organelles, each with a specific function. All of these structures are separated from the rest of the cellular content by a membrane. However, researchers have found that assemblies of molecules without a membrane are present in the cell as well. Some of these are formed as a response to cellular stress. This stress response is a consequence of intra- or extracellular triggers, which may cause harm to the cells. The subsequent formation of stress assemblies serves as an attempt to preserve large molecules during a period of stress.

Sec bodies and stress granules

In her thesis, Zhang mainly focuses on the formation and contents of two specific types of stress assemblies in Drosophila cells: Sec bodies and stress granules. Sec bodies on the one hand, develop from the coalescence of molecules in the outer parts of the endoplasmic reticulum One of the specialized structures in cells. The endoplasmic reticulum produces, among others, proteins. These proteins are activated in a different organelle: the Golgi apparatus.. On the other hand, stress granules arise from aggregation of RNA molecules and RNA-binding proteins. Both structures are reversible, which enables the cell to use the aggregated molecules again when the stressors have disappeared. Previous research had shown that both types of assemblies are formed when cells are deprived of amino acids, the building blocks of proteins. However, the underlying processes remained unknown. To get a better view on these molecular mechanisms, Zhang delved deeper in the signaling cascades leading to the formation of stress assemblies.

Characterizing stress assemblies

The first part of Zhang’s research is dedicated to the identification of signaling routes which cause the formation of Sec bodies. As such, she found out that amino acid deprivation and high levels of salt together lead to the activation of several enzymes A protein that accelerates a specific chemical reaction, for example the breakdown of a molecule. The enzyme itself remains intact in such a reaction, which enables the molecule to exert its function over and over again. Enzymes are present both in- and outside the cell. involved in the stress response of the cell. Eventually, the subsequent signaling cascade causes the formation of Sec bodies. In addition, Zhang describes how the absence of amino acids and presence of high levels of salt can induce the formation of stress granules. Interestingly, this is mediated by the activation factors that are different from the ones involved in the formation of Sec bodies.

Lastly, Zhang studied the content of Sec bodies to get an idea of which molecules are taken up in the stress assemblies. By using various techniques, she was able to identify 52 different proteins. A large proportion of these proteins originated from the endoplasmic reticulum or Golgi apparatus

Looking back

Zhang advises other PhD students to learn something from negative results, rather than only focusing on the result itself. She tells about her own trajectory: “It is always stressful and challenging to do a PhD. The most challenging thing for me was to make the work publishable: from experiment results to publication is a long way to go. Besides that, I also had a lot of exciting moments. Overall, I learned a lot and improved a lot over the past years.”

To celebrate obtaining her doctorate, Zhang will go on a short hiking trip in North Italy with her boyfriend. She adds: “Furthermore, I will go back to China to hug my family!”.