Systems Biology of Nodal Signaling

• Applicant: Professor Dr. Patrick Müller
• Subject Area: Developmental Biology
• Term: from 2013 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 230581876

My goal is to study how the interplay between the signaling molecules Nodal and Lefty leads to patterning in embryos using zebrafish as a model system. Nodal signals and feedback-induced Lefty antagonists are essential for germ layer patterning in all vertebrates. Misregulation of the Nodal pathway is frequently associated with birth defects and malignancies in humans. While genetic and embryological studies have shown that Nodal and Lefty have different activity ranges, the mechanistic basis for these differences has been elusive. I recently developed techniques to measure the biophysical parameters influencing the dispersal of fluorescently tagged Nodals and Leftys. I found that differential diffusivity, rather than stability, is the major determinant of the differences between the signaling ranges of Nodals (short- to medium-range) and Leftys (long-range). However, two major questions remain: 1) What factors account for the differential diffusivity of Nodal and Lefty? 2) How do Nodal and Lefty interact to proportionately pattern differently sized embryos? By addressing these questions, I will discover molecular mechanisms required for Nodal signaling, develop innovative quantitative approaches and test novel hypotheses addressing how the interplay between secreted signals and their antagonists patterns the embryo. My studies on the systems biology of Nodal signaling may also help to provide the necessary context for future therapeutic approaches.

• DFG Programme: Independent Junior Research Groups
• Major Instrumentation: Stereomicroscope with fluorescence
• Instrumentation Group: 5000 Labormikroskope