Nils Krietenstein

Project title

BASICS-3D: Biogenesis And Structure of Induced Compartments in Senescence in 3D

What is your project about?

Our genetic material, DNA, is identical across all the various cells in the human body. What differentiates a skin cell from a brain cell is the specific gene activity characteristic to each cell type. The processes that determine when and where genes are expressed are referred to as epigenetics. A significant aspect of epigenetic gene regulation is how our 2 meters of DNA are folded in three-dimensional space. Here, we focus on the senescent cell state induced by oncogene overexpression. This serves as a protective mechanism against cancer; however, over time, senescent cells can accumulate and contribute to aging and age-related diseases. A major reorganization of genome folding marks the transition into senescence. We will explore the relationship between three-dimensional genome organization and gene expression to understand how different cell types are established.

How did you become interested in your particular field of research?

How cell-types are established and maintained has fascinated me since my doctoral work. Our DNA must be accessible and dynamic to allow the expression of genes. At the same time, this structure must persist for a very long time to maintain a specific cell state. The profound impact of structural changes in tiny molecules on the function of cells – and, consequently, on the health of a human being – has always intrigued me. In particular, how the structure of genomes coordinates gene expression, in some cases over a human lifespan. Our work is at a fascinating junction between biochemistry, biophysics, and molecular medicine.

What are the scientific challenges and perspectives in your project?

Cell type-specific transcription programs are defined by many simultaneously acting epigenetic mechanisms. Understanding the impact of individual aspects is very important but challenging. The senescent cell model we are using in this project is ideal because many cells transition into the senescent state very homogeneously, which allows us to dissect the changes in epigenome reorganization in a time-resolved manner. Our cutting-edge technologies and the expertise of our collaborators will enable us to gain important insights into the question of how the topological structure of our heritable material shapes the identity of cells.

What is your estimate of the impact, which your project may have to society in the long term?

The ability of cells to senesce is an essential protection against cancer. Cells can transition into this non-functional state in response to the overexpression of an oncogene, rather than becoming cancerous. However, the accumulation of senescent cells in the human body is thought to be a major contributor to aging, as an excessive buildup of dysfunctional cells leads to organ dysfunction. Understanding and differentiating between how the senescence cell state is established and maintained is an important step toward clinical strategies to deplete these harmful cells and prevent aging.

Which impact do you expect the Sapere Aude programme will have on your career as a researcher?

The award of the Sapere Aude Starting grant will help to establish the Krietenstein lab in the Danish research landscape. We envision that our cutting-edge genomics technologies will be essential to local and global efforts to understand how cell types are established and maintained in health and disease.  
I believe that “blue sky” research is necessary. This project aims to understand basic molecular processes, which are essential for understanding how cells function. It enables us to connect detailed knowledge of how cells function with a broader goal: discovering insights that could ultimately contribute to improved medical treatments. This grant will play a key role in shaping the future of our research.

Background and personal life

I have always been passionate about science and traveling, and I feel fortunate that my career has taken me around the globe. I’ve had the opportunity to study and work in dynamic international environments in Germany, the USA, and Australia. In 2021, my partner and I moved to Denmark, where I established my research group. Since then, I’ve been surrounded by wonderful colleagues – young, enthusiastic, and collaborative. Copenhagen has truly become my home. I love the openness and warmth of the people here, and the city offers a great balance between professional ambition and personal well-being. Now, as a parent to my six-month-old daughter, I feel especially grateful to be raising her in a place that supports both family life and excellent science.