Stress Granules, Fjords and Kanelboller - a Research Internship in Norway

Written by Emily Locke

Hardly any other field of work thrives as much on international exchange as research. Networking and collaboration between researchers from all over the world are essential for scientific progress. Young, aspiring scientists in particular should therefore be encouraged to embark on research stays abroad - not only can they build important relationships for their future careers, but they also have the opportunity to explore a foreign country and get to know its culture and people.

Our student employee Emily seized such an opportunity in the summer of 2023 and traveled to Norway for an exciting research internship. There, she was part of a group at the University of Bergen that is investigating the cellular response to stress in the context of ageing and age-related diseases. Her three-month stay was supported by the RISE Worldwide program of the German Academic Exchange Service (DAAD). In this blog article, Emily reports on her research project as well as her travels and experiences in the "Land of the Fjords".

Arrival in Bergen - First Impressions

With around 270,000 inhabitants, Bergen is the second largest city in Norway after the capital Oslo - and in my opinion also one of the most beautiful! It is situated in an idyllic location on the west coast of the country and is rightly known as the "Gateway to the Fjords" (Fig. 1). The natural harbor with the fish market and Bryggen form the heart of the city. Bryggen (Norwegian for landing stage) is a district consisting of old Hanseatic trading establishments. It was declared a UNESCO World Heritage Site in 1979 as an example of Hanseatic architecture in Norway. In addition to the harbor district, the surrounding mountains characterize the cityscape and are ideal for hiking or - in the case of the athletic Norwegians - rather for trail running.

Bergen is also known as Syvfjellsbyen, the "city of the seven hills", although the exact number is debatable. During my stay, I climbed each of the seven mountains that are also hiked as part of the 7-fjellsturen (7-hill tour) organized annually by the Norwegian Hiking Association. These include Ulriken, which is the highest of the seven mountains at a proud 643 meters. But Bergen doesn't just offer impressive nature, a stroll through the small streets of the town can also be highly recommended. There are cute cafés on many corners where you can take a break - in typical Norwegian style with a filter coffee and a freshly baked Kanelboller, of course!

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Figure 1: Bergen from above. Beware, these pictures might be deceiving! The nice weather you see here is a rare occurrence in Bergen: with around 240 rainy days a year, the Norwegian city is the rainiest city in Europe. But when the sun does come out for a change, it's all the more beautiful!

Cells under Stress: the Importance of Stress Granules

But enough about the beauty of Bergen - after all, I was there to do research! I had the great opportunity to work in Prof. Sushma-Nagaraja Grellscheid's group at the Department of Biological Sciences at the University of Bergen. Prof. Grellscheid and her team are interested in biomolecular condensates and their biophysical properties in particular. Biomolecular condensates are organelles that are devoid of lipid membranes. A well-known example is the nucleolus, a specific area in the cell nucleus that serves as the site of ribosomal biogenesis. The membraneless organelles consist of biomolecules such as proteins and nucleic acids and are considered to be liquid-like droplets that coexist with the cytoplasm. They are formed by a process known as liquid-liquid phase separation, or LLPS for short. LLPS is caused by multivalent interactions between proteins and RNA, which promote the transition of a protein into another phase with altered physiochemical properties.

My project focused on a specific type of biomolecular condensates, referred to as stress granules. They are formed by the cell in response to external stress stimuli (e.g. heat, nutrient shortage, toxins or viral infection) and consist of mRNA and a large number of different proteins. The sequestration of mRNA into stress granules reduces protein biosynthesis, thereby saving resources. Although the condensates are essential for the normal functioning of the cell and for its survival of suboptimal environmental conditions, recent studies suggest that persistent stress granules resulting from chronic stress play an important role in aging and age-related diseases. These include neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), as well as cancer. Therefore, researchers are interested in better understanding the molecular mechanisms of stress granule formation and their biophysical properties.

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Figure 2: Research project on stress granules. Left: Fluorescence microscopy image of U-2 OS cells treated with sodium arsenite. The stress granules are clearly visible due to the GFP labeling. Right: My daily outfit in the cell culture room.

This is also the aim of Prof. Grellscheid's group. My project focused on investigating how metabolic pathways change with age and how this affects stress granule formation. I worked with a U-2 OS cell line that contains a GFP-tagged G3BP1 protein. G3BP1 is one of the proteins that are essential for the assembly of stress granules. Fluorescence labeling makes it possible to track the formation and shape of the granules with a fluorescence microscope (Fig. 2). In order to be able to interpret our findings in the context of age-related diseases, we used senescence as a model of ageing in addition to young, proliferating cells. For my experiments, I treated the cells with sodium arsenite, an inorganic compound that triggers oxidative stress and thus initiates stress granule assembly (Fig. 2). My results reveal differences in the metabolic regulation of stress granules in senescent cells.

Stressed Cells, but no stressed Scientists - Research in Norway

Academic research in Germany often has the reputation of involving a lot of overtime, poor pay and work on the weekend. Norway showed me that things can be different: there is very little overtime, even as a PhD student you get a decent salary and weekends are free (as they should be). This may not apply to all positions, but overall, I had the impression that working conditions as a researcher in the Nordic country are much better than in Germany.

In addition, you can spend your free time relaxing in the great outdoors. Norway really has more than enough to offer - so if you like outdoor activities of any kind, the Scandinavian country is a great place to be! Since I love hiking, Norway was a paradise for me: After work, I was able to climb one of the local mountains in Bergen and on the weekends, I went on longer hikes in the surrounding national parks (Fig. 3). Huge glaciers, steep mountains and deep blue fjords - the wild landscape is really impressive!  In winter, with a bit of luck, you can even see the Northern Lights in Bergen. Unfortunately, I missed this impressive natural spectacle - one more reason to come back to Norway soon!

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Figure 3: The beauty of Norway. Top left: One of the most famous photo spots in the country: Trolltunga, the Troll Tongue. Top right: Fjord view from Preikestolen. Bottom left: The Jostedalsbreen glacier. Bottom right: The skyline of Oslo, Norway's capital.

Tags: Biomol