Most people have heard of the abbreviation “mRNA” – which stands for “messenger ribonucleic acid” – simply because of its importance in developing the latest Covid-19 vaccines. But what is it actually? Sutapa Chakrabarti who is a biochemist and studies mRNA in her research explains, “mRNA molecules transfer the ‘blueprints’ for proteins that are stored in the cell nucleus from our genetic material – in other words, our DNA – to ribosomes, the protein factories of the cell. Essential proteins are produced here according to those instructions. Without them, the human body simply wouldn’t function.”

mRNA molecules and the role they play in organisms have been an important topic of study since they were first discovered in 1961. Chakrabarti, together with her working group, is investigating how mRNA disappears from eukaryotic cells (which are found in plants, fungi, animals, and humans) when the proteins are no longer needed. Since 2022, she has been funded by the German Research Foundation’s Heisenberg Program, which paves the way for a professorship without having to undertake an additional qualification to teach at a German university.

mRNA Assemblies under the Cryo Electron Microscope

“The easiest way to stop protein production is for the mRNA – which has these blueprints – to disappear from the cell,” she continues. But what are the enzymes needed for this? And how do they receive the signals from cells to break down the mRNA? In order to understand the process, Chakrabarti observes and reconstructs the architecture of the molecules involved in the individual stages.

X-ray crystallography was her primary method of analysis up until a few years ago, but recently cryo electron microscopy has advanced so much that the progress in structural biology is astounding. In order to capture these flexible molecular arrangements without damaging them, they have to be frozen extremely quickly using a method known as “flash freezing.” Then electrons are fired at frozen samples. The resulting images allow researchers to then calculate three-dimensional structures at different stages.

Chakrabarti is currently researching a process that is responsible for controlling the levels of cytokines, among other proteins. These proteins alert cells in our immune system when foreign substances enter our bodies. However, only a small amount of these proteins needs to be produced and that needs to happen over a limited period of time– basically only for as long as it takes for the immune cells to do what they need to do. Chronic inflammation and autoimmune diseases can develop if cytokine production isn’t stopped, so there needs to be a rapid switch from protein production to degradation of the mRNA.

Experimentation Requires Keeping All the Plates Spinning

“I’m mostly interested in how this switch happens,” says Chakrabarti. “A remarkably simple mRNA component is actually responsible for this process, but just like everything else in biochemistry, it’s all much more complex than you initially assume.” While this makes the subject all the more fascinating, it can also lead to frustration. Chakrabarti adds, “Nothing in biochemistry is exact or precise. The more we investigate, the more complicated it gets. Models are very popular in science – but it’s important not to confuse them with reality. That was an important lesson for me to learn.”

Scientific breakthroughs make her profession incredibly rewarding, but she also has a lot of fun working with young people. “I love meeting enthusiastic bachelor’s students who can hardly wait to get into the lab.” Yet once they get there, they may soon find that it can take months for an experiment to actually work. Chakrabarti sometimes has to jump in and give her mentees a pep talk. She explains that this is a totally normal part of the process and that they shouldn’t take it personally. Their best bet is often to get back to work, go through the relevant literature, and wait to see how things turn out. Keeping all the plates spinning is a crucial aspect of experimentation: “You have to keep an eye on every single detail, while subconsciously processing what exactly is going on in the experiment at the same time.”

Delhi, Mumbai, San Diego, Martinsried...

Chakrabarti actually wanted to be a physician like her parents when she was little. She later developed an interest in literature, but it was common at the time for children with good grades to go into the sciences. She was also very interested in chemistry, and so decided to pursue it at Delhi University. She then went on to do a master’s degree in biotechnology in Mumbai and later moved to San Diego for her PhD at the University of California San Diego.

“My parents encouraged me to go abroad, but they also gave me the space to decide for myself. That is still rather unusual for some families in India,” she adds. Her PhD supervisor expected quite a lot from her, but also gave her plenty of support when it came to planning her career. She started off with a postdoc position at the Max Planck Institute of Biochemistry in Martinsried on the outskirts of Munich, before becoming a junior professor at the Institute of Chemistry and Biochemistry at Freie Universität Berlin in 2014.

...And Now at Home in Berlin

Chakrabarti will stay put for the time being; Berlin has become home and her daughter goes to kindergarten here. While she enjoys hopping from city to city and working in different places, having a little bit more stability has done her the world of good. “Right now, my doctoral students don’t have to worry that one day I’ll just pack up and leave for somewhere else,” she says. This allows her to think, plan, and set up collaborative projects in the long term.

What she likes about Berlin is that it’s highly diverse, cosmopolitan, and a little bit eccentric. Chakrabarti is particularly impressed by the history of this once-divided city; the peaceful reunification process gives her hope that other conflicts across the world can be resolved in the future. In the little free time she has, she enjoys reading and taking walks in nature. “I don’t have to go very far to experience natural beauty. Sometimes I just get off the bus a few stops earlier and walk through Dahlem.”

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This article originally appeared in German on September 6, 2022, in campus.leben, the online magazine of Freie Universität Berlin.