Composition stoichiometry of CD95/Fas complexes as a switch between life and death

• Applicant: Professorin Dr. Inna Lavrik
• Subject Area: Cell Biology
• Term: since 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 260615047

Programmed cell death is a highly regulated process which is essential for all multicellular organisms. The deregulation of cell death leads to a number of diseases such as cancer, neurodegenerative and autoimmune diseases. There are two major types of programmed cell death: apoptosis and necroptosis that could be initiated upon ligation of death receptors (DR). CD95/Fas/APO-1 is one of the best-studied members of the DR family. Stimulation of CD95 has been reported to result not only in the cell death but also in the induction of a number of survival/proliferation pathways such as NF-kB. The induction of a particular CD95 pathway is crucially dependent on the formation of the corresponding signaling platform or multiprotein complex. The proposal will be devoted to the analysis composition stoichiometry, posttranslational modifications (PTMs) and search for new molecules of CD95 molecular platforms regulating the switch between apoptosis, necroptosis and NF-kB. We will use highly innovative approaches in our work: from the contemporary Mass Spectrometry analysis to the single cell measurements. The isolation of the complexes will be followed to the established state of the art in the field and would involve high molecular weight fractionation. Our studies should provide a new information on molecular mechanisms of the CD95 network regulation and shed the light on the question how these signaling platforms could potentially be targeted in the context of disease.

• DFG Programme: Research Grants