In-vivo Drug Interaction of Cytochrome P450 probed by resonant enhanced Coherent anti-Stokes Raman Scattering (CARS) Microscopy

• Applicant: Dr. Marcel Günther Friedrich
• Subject Area: Biophysics
• Term: Funded in 2007
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 36624835

Cytochromes P450 are NAD(P)H dependent, 6-type heme containing monooxygenases that catalyse a variety of reactions in the human organism. They provide the primary defensive system against xenobiotics, they are involved in the metabolism of more than 80% of all currently used drugs and they are main target in current cancer therapies. The proposed work comprises the development of an in-vivo method to visualize the activity of Cytochrome P450 in living cells. Coherent anti-Stokes Raman scattering microscopy is a novel and powerful tool that overcomes the disadvantages of conventional vibration Spectroscopy. This nonlinear technique utilizes vibrational contrast, which permits rapid and non-invasive in vivo imaging with high chemical sensitivity and selectivity as well as a high threedimensional spatial resolution. The aim of this project is to extend this technique for the first time into the field of heme proteins in order to study pharmacological aspects with clinical relevance on a molecular level, such as the metabolism of drugs, drug interactions, enzyme-ligand interactions or processes occurring during cancer evolution. This will be investigated in detail as a function of different parameters, such as concentrations of different drugs or carcinogens, oxygen content and different cell types. Moreover, the investigation could yield a better understanding of processes related to the evolution of cancer for examples as a consequence of outer factors, such as drugs or chemicals compounds.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Xiaoliang Sunney Xie