Molecular mechanisms regulating adult intestinal stem cells

Throughout life, the human body undergoes repeated stress and damage due to multiple reasons: a natural wear and tear process, ageing, illnesses or injury. In order to maintain their functionality, our organs and tissues require a process of constant renewal. The tissues ability to self-repair is ensured by the presence of undifferentiated cells, termed stem cells. Whenever necessary, tissue-specific stem cells divide, producing numerous cells that acquire specialised characteristics (a process known as differentiation) and replenish the damaged areas of the tissue they belong to. The mammalian intestine is a unique system to study stem cell biology: in the mouse it is estimated that the entire intestine self-renews every 3-5 days. Intestinal stem cells actively divide to replace damaged or dead cells, so that the intestine can maintain its important absorptive functions. What are the mechanisms that regulate stem cell activity? Numerous studies have shown that the presence of certain signals will determine if stem cells can activate and divide, or remain quiescent. Importantly, cells also adopt safety mechanisms that prevent unrestricted proliferation. Serious diseases, like cancer, arise when these mechanisms fail to work. While many of the genetic mechanisms governing stem cells are known, there is still much to learn. With this project, I aim to study the biochemical language that stem cells adopt to communicate to each other, and which regulate their activity. During my study, I will use novel biochemical and proteomic methods that allow to identify an entire network of proteins involved in a specific process. Findings from this research will be tested using mini-gut organoids, which are special stem- cell derived 3D structures that mimic the actual intestinal tissue. This work would not be possible without the generous funding by the FWF Lise Meitner Program, and will benefit from the experience of a leader in the stem cell field, Dr Bon-Kyoung Koo, as well as a top research institute, such as the Institute of Molecular Biotechnology (IMBA) in Vienna.

No additional funding sources recorded.