When cells lose their bookmarks
Returning to the book analogy, this is kind of like scrambling an entire, carefully organized system of bookmarks. One might expect cells to lose track of which “chapters” they are supposed to read, severely disrupting normal tissue function or even promoting cancer. Surprisingly, that was not what happened. Many tissues continued to function remarkably normally, even when microRNA activity was blocked. The importance of those “bookmarks” became apparent when tissues were challenged and needed to regenerate. Under these conditions, microRNAs suddenly became essential.
Do microRNAs work on demand?
This suggested something intriguing: perhaps cells do not rely as heavily on microRNAs as previously assumed. Instead, we may need to reconsider their role, not as a system that continuously fine-tunes gene expression, but as a molecular switch that cells can turn on when they need to rapidly adapt to change, such as during wound healing. This observation informed a fundamental question that fascinated me: Could microRNAs be particularly important not for maintaining a cell’s identity as previously thought - but instead for actually suppressing it, allowing it to change its behavior or even adopt a new identity when needed?
Wound healing provides a great system to investigate this idea. Following an injury, regenerative cells in the skin must rapidly adapt to changing conditions. They multiply, migrate into the wound, and can even alter aspects of their identity to repair damaged tissue.
Advances in methodology
To investigate the role of microRNAs in this process, I developed a new mouse model that allows microRNA activity to be temporarily switched off specifically in the regenerative cells of the skin. The Erwin Schrödinger Fellowship was instrumental in making this research possible. Moving to Memorial Sloan Kettering Cancer Center gave me the opportunity not only to pursue these questions in one of the world’s leading cancer research environments, but also to learn new experimental techniques. For example, I was trained in genetically manipulating mouse embryonic stem cells and use them to generate genetically engineered mouse models.
A Mouse Model crosses the Atlantic
What makes the Erwin Schrödinger Fellowship particularly special is that it enables researchers not only to acquire new knowledge and skills abroad, but also to bring them back to Austria. In my case, this transfer was quite literal: the genetically engineered mice I developed in New York made the journey across the Atlantic to Vienna.
Today, I am using this mouse model in the Ogrodnik Laboratory at the Ludwig Boltzmann Institute for Traumatology to investigate a deceptively simple question: Which cellular processes in the skin actually depend on microRNA activity, and why?
By better understanding when and how cells rely on this molecular machinery, I hope to uncover fundamental principles of how cells adapt to change, with potential implications for our understanding of tissue regeneration, aging and cancer.
