9 June 2022

Thesis defense Wessel van Leeuwen: “Stress granules and Sec bodies, from Drosophila to mammalian cells”

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Wessel van Leeuwen – from the group of Catherine Rabouille – successfully defended his PhD thesis “Stress granules and Sec bodies, from Drosophila to mammalian cells” on the 9th of June 2022. He focused on cellular stress, a process that is initiated by harmful internal or external stimuli. Van Leeuwen delved deeper into the formation and content of stress assemblies that are meant to protect important molecules during periods of stress in the cell. He did so by studying two types of stress assemblies; stress granules and Sec bodies. Van Leeuwen identified various RNA molecules that are present in the stress granules. Furthermore, he was the first to confirm the formation of Sec bodies in mammalian cells. This information provides a foundation that researchers can use to further study and understand the function of stress assemblies during stress.

When cells are triggered by harmful circumstances, a stress response is initiated as an attempt for the cell to survive. Such a stress response results in a wide variety of molecular changes, amongst which the aggregation of large molecules in stress assemblies. These structures lack a membrane, whereas most other structures in the cell do have one to separate their content from the rest of the cell. Once the signals that induced the stress response have disappeared, the stress assemblies are quickly dissolved. The liberated molecules can be used again in the normal cellular processes. During his PhD, Van Leeuwen tried to get a better view on stress assemblies in Drosophila and mammalian cells. Using various strategies, he was able to identify several aspects of Sec bodies and stress granules: two specific types of stress assemblies.

TRIBE to study RNA content

The first step in Van Leeuwen’s research was the identification of RNA molecules, abundantly present in stress granules. For this purpose, he made use of TRIBE: an advanced technique that can be used to specifically label the RNA molecules within stress granules. A great benefit of this strategy was the possibility to study single cells and limited tissue, such as neurons. This gave a detailed insight into the RNA-content of stress granules. With these experiments, Van Leeuwen showed that TRIBE is a powerful tool for studying the RNA content of stress granules. This opens up the possibility to study the RNA content of other stress assemblies as well.

Sec bodies in mammalian cells

All previous research on Sec bodies was done in Drosophila cells. Van Leeuwen therefore questioned whether mammalian cells respond similarly to stress signals. In his thesis, he provides evidence that mammalian cells are able to form Sec bodies that have similar characteristics as those in Drosophila cells. This is the first time that Sec bodies have been found in mammalian cells.

“Believe in yourself”

Van Leeuwen describes his PhD as a mixture of both exciting moments and various setbacks. However, he emphasizes the good memories: “Overall, I learned a lot and I am proud of the obtained results. The biggest highlights of my trajectory were mostly before the COVID-situation; I always liked the PhD-retreat, masterclass and discussions about science with colleagues. I have met friendly people and had fun times with them!”

Although a PhD can be tough sometimes, Van Leeuwen gives other students the advice to keep your head up: “Believe in yourself and in your own ideas. Do not give up and push until you have tried everything.”

 

 

Wessel van Leeuwen is currently working as a Data Scientist for Global Factories in The Hague. His role is to process and analyze data from machines that are used for medication packaging and verification at pharmacies.