Forskning ved Københavns Universitet - Københavns Universitet

Michael Lund Nielsen
Michael Lund Nielsen

professor, gruppeleder

An emerging concept of modern biology relates to the systematic understanding of cellular networks co-regulated via post-translational modifications (PTMs). The research focus of the Nielsen group is to develop novel proteomics methods and technologies for studying underexplored PTMs on a systems-level approach. Such developments allows the Nielsen group to elucidate hitherto uncharacterized PTMs and provide a better understanding of their biological implications in human cells, while uncovering the functional impact they exert in cellular phenotypes and diseases. Key achievement in this field is the development of proteomic strategies for analysis of endogenous SUMOylation, arginine methylation and ADP-ribosylation in a systems-wide manner. These methods has allowed the Nielsen group to investigate these emerging PTMs at an endogenous level, thus positions the group with unique analytical capabilities for studying the modifications in a range of cellular and biological conditions. Most recently, the Nielsen group has focused on exploring the cellular extent of ADP-ribosylation catalyzed via the nuclear ADP-ribosyltransferase PARP1. As PARP1 is associated with the occurrence and progression of various diseases, PARP inhibitors aimed at interfering with ADP-ribosylation catalyzed by PARP1 are commonly used for medical interventions. While the enzymatic function and cellular implications of PARP inhibitors remains elusive, the Nielsen group now utilizes its leading technology to pinpoint the protein targets of PARP1. Following this, the group established that serine residues are the preferred acceptor site of PARP1 on a proteome-wide scale, exemplifying the analytical advantages of generating powerful data resources for elucidation of uncharacterized PTMs using high-resolution mass spectrometry.

ID: 13143239