Dr. Natalie Krahmer

Proteomics: an overview of a cell’s line-up of players

Contacts, position changes, interactions, interplay − when Dr. Natalie Krahmer talks about her research it sounds like a discussion about tactics in her favorite sport, soccer. Using proteomics, she analyzes what occurs inside cells. She is particularly interested in how the organization and composition of individual cell compartments changes and which signaling pathways are active during the development of metabolic diseases. Since January 2019, she has headed an Emmy Noether* junior research group at Helmholtz Zentrum München, for which she has been granted 1.8 million euros in funding over six years by the German Research Foundation (DFG).

 

Dr. Natalie Krahmer. © Helmholtz Zentrum München

Cellular organelles provide functionally separate compartments for various biochemical reactions and are highly dynamic structures. By altering their protein and lipid compositions, biochemical activities and their interactions with other organelles, they are able to adapt to changing environmental demands. However, an oversupply of nutrients over a protracted period causes cellular stress. The consequences are obesity and metabolic diseases such as diabetes.

Exploring the tactics of organelles

This is where Krahmer plans to start with the work of her junior research group: By combining proteomics** and cell biology, she wants to discover changes in subcellular organization during the development of metabolic diseases, specifically in non-alcoholic fatty liver (hepatic steatosis).

“We still don’t fully understand how the development of metabolic diseases affects the interaction between cell organelles, how they reorganize and how these processes are regulated by proteins and signaling pathways in different organs and tissues. We want to use proteomics to shed light on these processes and understand what happens in the cell when lipids accumulate or when insulin resistance or diabetes develops,” the scientist says, describing her goal.

What particularly fascinates her about proteomics is that it allows to observe all proteins in a cell at the same time. “That gives us a completely unbiased view into the cell and is yielding surprising new findings and can lead to the discovery of new therapeutic targets,” Krahmer says.

Together with her junior research group, she wants to build on previous findings, which showed that excessive cellular lipid accumulation, as occurs in fatty liver, alters the interaction between organelles and impairs the liver’s secretory pathways. Using mass spectrometry and innovative phosphoproteomic workflows, she also wants to identify still unknown proteins involved in the signaling pathway of the satiety hormone leptin and factors for the development of resistance to it.

Enthusiasm for the interaction of proteins and cell organelles

She chanced upon protein biochemistry during an internship when she was studying biology at the Technical University of Munich (TUM). It was in the laboratory of Professor Peter Walter at the University of California at San Francisco. “We looked at how proteins in the endoplasmic reticulum fold. I was immediately excited to be able to observe what’s happening inside a cell and how proteins and cell organelles interact,” Krahmer says. Such enthusiasm is reflected in further stages of her career. For example, during her doctoral thesis under Professor Tobias Walther of the Max Planck Institute of Biochemistry in Martinsried and the Yale School of Medicine, she addressed the question of how proteins bind to lipid droplets in cells and how the process is regulated.

As a postdoc in the Max Planck laboratory of Professor Matthias Mann, known the world over for his proteomics research, she achieved a special milestone: “By analyzing cell organelles of a fatty liver, we discovered that if too many lipids accumulate in the liver, the Golgi apparatus, which is important for secretion, fragments and binds to lipid droplets. That was a new finding, and it shows how strongly cell organelles are affected by external metabolic factors,” Krahmer says. “Previously, with microscopy, single proteins were studied separately in a cell. With proteomics, we can now detect all the proteins and their cellular localizations at the same time and under the same conditions. This enables us to identify such general effects more easily than by looking at individual proteins.”

Proteomics: the tactic for investigating metabolic processes

Krahmer’s junior research group is based at the Institute for Diabetes and Obesity (IDO) of Helmholtz Zentrum München. With her expertise in proteomics, she wants to investigate metabolic processes involved in the development of diabetes. “I have the feeling that relatively little in the way of proteomics is being applied in the field of diabetes research, and I think that that will open up whole new possibilities for us. I’m excited about what the field holds in store,” she says. Thanks to her proteomics knowhow, Krahmer is already a sought-after collaborator for other researchers at Helmholtz Zentrum München.

Krahmer showed herself to be open-minded and determined at an early age when she was the only girl on her neighbor’s soccer team. With her passion for soccer, as a teenager she even made it into the Bayernauswahl, a selection of top soccer talents from across Bavaria. Today, the mother of two still plays outdoor sports to counterbalance the mental work. She gets out and about as much as possible with her family to draw energy for the upcoming scientific challenges at Helmholtz Zentrum München.

* The Emmy Noether grant program of the German Research Foundation gives specially qualified junior scientists an opportunity to qualify for a university professorship over a period of six years by assuming responsibility for a junior research group. www.dfg.de

** Proteomics is the study of the proteome using biochemical methods. The proteome is the sum total of all proteins in a cell or a living animal at a defined time and under defined conditions. The proteome and the transcriptome are dynamic in that their qualitative and quantitative protein composition can change in response to shifting conditions (environmental factors, temperature, gene expression, drugs, etc.). Proteomics aims to catalog all the proteins in an organism and identify their functions.

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