- Dipl. degree, Johannes Gutenberg-University Mainz, Germany
- Dr. rer. nat., Johannes Gutenberg-University Mainz
- Dr. habil., University of Osnabrück, Germany
- Dr. habil., University of the Saarland, Germany
- Group leader, University of the Saarland, Institute of Biophysics, Germany
- Habilitation-Fellow, University of Osnabrück, Department Biology & Chemistry, Germany
- Research associate, University of Osnabrück, Department Biology & Chemistry, Germany
- Postdoctoral-Fellow (HFSP), University of Osnabrück, Department Biology & Chemistry, Germany
- Postdoctoral-Fellow (DAAD), University of Oregon, Institute of Molecular Biology, Eugene, USA
Structure and mechanism of molecular motors and sensors
ATP synthases are the smallest biological motors, which produce the molecule ATP (adenosine triphosphate), the common energy currency of cells. When biological cells require energy, they “spend” ATP. A typical 70 kg human with a relatively sedentary lifestyle will generate around 2.0 million kg in a 75-year lifespan. Therefore, it is of great interest whether the member of this ubiquitous protein superfamily have conserved pattern, making them efficient molecular machines. High efficient machines can be invented by inspiration of the amazing biomolecular motors in nanometer size. A motor requires specific interactions between its parts and a catalytic interaction with its fuel molecule. One way to design such machines might be to assemble new motors from the pre-existing “unit machines”- protein domains with known structure and behavior that can be combined without much change in their properties. As ATP is the metabolic currency, ATP synthases are associated directly or indirectly with various human diseases like Leigh syndrome, cancer, Alzheimer’s and Batten’s disease. Therefore, ATP synthases are a good molecular target for drugs in the treatment of various diseases like tuberculosis and the regulation of energy metabolism. Because of the significance of these biological motors to cell physiology, nanotechnology and medicine our laboratory is interested to understand the structural, mechanistic and regulatory elements of the two main energy producer A1AO ATP synthase and F1FO ATP synthase.
Whereas ATP synthases produce ATP, the enzyme class of ATPases consumes ATP and cleaves it to ADP and Pi, to transport ions or molecules like DNA and RNA and can be called as energy transducer. Vacuolar ATPases (V-ATPase) are nature’s most versatile pump as they participate in a wide variety of cellular processes including endocytosis, intracellular transport, membrane fusion, bone resorption, and renal acid-base balance. V-ATPases have crucial functions in many pathophysiological processes which indicate, that they are prime targets in the development of therapies for diseases such as osteoporosis and cancer. We are engaged to understand how vacuolar ATPases function and how they are controlled These informations will provide important clues for the development of such therapies.
The nucleotides ATP and ADP are also signal molecules in biological processes as in the invasion of the malaria parasite into the red blood cell. A sensor protein of the parasite sensors the level of nucleotides, followed by conformational alterations in the protein with the consequent interaction with a receptor of the red blood cell. Insight into the structural traits of the sensor will help to identify new compounds that directly interfere with the invasion process.