Magdalena Paolino

Project summary

Ubiquitination and intestinal stem cells

Magdalena Paolino studies ubiquitination, a process that regulates many important events within the cell. She is particularly interested in its role in intestinal stem cells. The findings from the project may help us understand how the intestinal lining is continuously renewed, as well as how intestinal cancer develops.

 

Ubiquitin is a small regulatory protein found in most of our cells. It performs its function by attaching to other proteins, a process known as ubiquitination, thereby regulating several fundamental cellular processes. The effect of ubiquitination on a protein depends both on how ubiquitin is attached and on the number of ubiquitin molecules added to the protein. Since a range of diseases originate from defective ubiquitination, it is important to gain a better understanding of the molecular and cellular processes regulated by ubiquitin. In particular, we still do not know how the different types of ubiquitin chains found in cells function. The less common linkages, known as atypical ubiquitin chains, have remained largely unexplored.

 

The project aims to identify new functions and mechanisms of atypical ubiquitin chains. Preliminary data indicate that the cellular processes regulating intestinal stem cells are altered when atypical ubiquitination is disrupted. Changes in intestinal stem cells not only affect the continuous renewal of the outermost cell layer of the intestine but may also lead to intestinal cancer. The project aims to provide mechanistic insights into how intestinal stem cells function, using state-of-the-art genetic, cellular and molecular methods. The ultimate goal is to establish the biological relevance of atypical ubiquitin chains, which may also open up new approaches to regenerative medicine and the treatment of intestinal cancer.