Dr. Michael Lammers

Principal Investigator – Junior Research Group Leader, Institute for Genetics

Dr. Michael Lammers
Principal Investigator – Junior Research Group Leader, Institute for Genetics
Tel.  +49 221 478 84308

CECAD Cologne
CECAD Forschungszentrum
Joseph-Stelzmann-Str. 26
50931 Köln
Profile Page

Michael Lammers

Dr. Michael Lammers and his team explore the regulation of protein function by post-translational acetylation of lysine side chains. The group’s focus is on the regulation of the cytoskeleton. They have successfully incorporated acetyl-lysine site-specifically into different proteins. In the future, using this strategy might allow the working group to develop novel therapeutic approaches including the design of deacetylase inhibitors with fewer side effects compared to known compounds.

Our research: Dr. Lammers and his team explore how lysine-acetylation regulates protein function. Acetylation of lysine side chains is one of the most abundant post-translational modifications comparable in number to phosphorylation. It is dynamically regulated by lysine-acetyltransferases and lysine-deacetylases. The focus of Dr. Lammers and his team is how the cytoskeleton is regulated by lysine-acetylation. The cytoskeleton is involved in many processes essential to the cells’ survival. A dysregulation thereof can have drastic consequences for the cellular fate supporting processes such as tumor formation and neurodegenerative cellular disorders.

Our successes: Dr. Lammers and his researchers have observed that these post-translational modifications regulate protein function in a range of different ways. Lysine-acetylation can confer a loss-of- as well as a gain-of-protein function by recruiting bromodomain-containing proteins. Thereby, these processes can lead to modulations of cellular signal transduction pathways.

Our goals: Dr. Lammers long-term goal is to therapeutically tackle the molecular lysine-acetylation machinery. Deacetylase inhibitors have been subject of intensive basic research but they are also in clinical trials in pharmaceutical industry for several years now. However, these compounds often have a low level of target specificity and they show a broad range of unwanted off-target effects. His group focuses on developing more specific therapeutic agents with less side-effects. Mechanistic inhibitors based on non-cleavable acetyl-lysine analogs, such as thioacetyl-lysine, could be used to synthesize highly effective lysine-deacetylase inhibitors.

Our methods/techniques: A range of different biochemical and biophysical methods are used in the lab, including isothermal titration calorimetry, stopped flow, microscale thermophoresis and X-ray crystallography.

Figure 1
Figure 2

Figure 1: Structural and functional studies of the effect of lysine-acetylation on cytoskeletal protein function.
(A) We study the influence of lysine-acetylation on the thermodynamics and kinetics of protein-protein interactions and on the protein-structure (B). (C) We study the impact of lysine-acetylation in eukaryotic cells (D) and want to understand how lysine-acetylation is regulated by KDACs, KATs and targeted by  BRD-containing proteins.

Figure 2: The genetic-code expansion concept. (A) We use a synthetically evolved acetyl-lysyl-tRNA-synthetase/tRNACUA pair from Methanosarcina bakeri to site-specifically incorporate N-(ε)-acetyl-L-lysine into proteins. (B) Acetylation is a highly dynamic post-translational modification.

EXTERNAL Cooperations
  • Prof. Dr. U. Baumann, Institute for Biochemistry, University of Cologne, DE
  • Dr. J. Chin, MRC/LMB Cambridge, UK
  • Dr. L. James, MRC/LMB Cambridge, UK
  • Prof. Dr. I. Neundorf, Institute for Biochemistry, University of Cologne, DE
  • Prof. Dr. T. Outeiro, University Medical Center, Göttingen, DE
  • Dr. G. Praefcke, Paul-Ehrlich-Institute, Langen, DE
  • Em. Prof. Dr. A. Wittinghofer, MPI of molecular Physiology, Dortmund, DE