Principal Investigator, Institute for Biochemistry I
Prof. Dr. Noegel’s research group focuses on the cytoskeleton, a component of the cell responsible for mechanical stability and signal transmission inside the cell. A group of proteins, which are anchored in the nuclear envelope, bind the actin filaments of the cytoskeleton. The destruction of these links can cause diseases such as laminopathies. Deficiencies of another protein-group, which are found in the M-band of myofilaments, can result in muscle damage, which can trigger cardiomyopathies and other diseases. The group’s second research focus is on genetic defects of the centrosome.
Our research: In eukaryotic cells, the nuclear envelope separates the chromosomes from the cytoplasm. Proteins, such as the Nesprins found in the nucleus, fulfill key cell functions. They link the cytoskeleton and the centrosome to the nucleus, thus stabilizing the nucleus. They also modulate signal transduction, and thus are involved in processes of aging. Dysfunctions trigger aging-associated diseases, such as delayed wound healing and muscle damage in the form of cardiomyopathies.
Our successes: One breakthrough by Prof. Noegel’s group was the description of Nesprin-1 and -2 as new components of the nuclear envelope, which connect the nucleus to the cytoplasm and cytoskeleton.
Another exciting result was the portrayal of the link between the SUN proteins, inner nuclear membrane proteins, and the Nesprins (proteins in the outer nuclear membrane) which together form the LINC complex. Furthermore,in a successful collaborative project with Prof. Nürnberg, mutations of centromere components were identified as the cause of microcephalies, a failure in cerebral cortex growth.
Our goals: Prof. Noegel’s working group explores the principles of cytoskeleton and centrosome regulation. Their research centers on the role of the proteins and the illnesses associated with dysfunctions.
Our methods/techniques: Prof. Noegel’s team uses biochemical experimental methods to investigate interactions at the protein level. The biological relevance of the findings is then tested in mouse models.
Figure 1: Structure of the D. discoideum coronin CRIB domain. The 3D structure of D discoideum coronin was predicted using SWISS-MODEL program using murine coronin 1 (PDB code 2AQ5) as a template. The top view of the modeled D. discoideum coronin is shown.
The CRIB domain is highlighted in red and the corresponding strands are labeled. The figure was generated using Jmol (Jmol: anopen-source Java viewer for chemical structures in 3D. www.jmol.org) (taken from Swaminathan et al., 2014).