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Systems biology of development

Patrick Müller

Patrick Müller

  • Diplom studies in Göttingen, Berkeley, New York, 1999-2004
  • Ph.D. studies at the MPI for Biophysical Chemistry, 2004-2007
  • Postdoctoral fellow and research associate at Harvard University, 2007-2013
  • Emmy Noether independent research group leader at the MPI, since 2013

Research Interest

How do extracellular signaling molecules pattern developing embryos and tissues? We use zebrafish and flies as model systems and combine genetic, biophysical, and theoretical approaches to address this question. Our research focuses on three areas:

i) Biophysics of signal dispersal
Multiple signaling pathways need to be precisely coordinated in space and time to pattern the body plan. How are the appropriate distributions of signaling molecules achieved such that cells receive the right amount of signal at the right time? What factors regulate the diffusion and stability of signals?

ii) Self-organization of patterning
Systems of signals that diffuse and react with each other (reaction-diffusion systems) have been postulated to underlie complex self-organizing patterns. How might such systems function in living embryos? How do signaling systems concertedly coordinate proper patterning?

iii) Scale-invariant patterning
Individuals of the same species can vary considerably in size, but the proportions of their body plans are often constant. How is the spatial range of signaling molecules regulated during development to establish the correct tissue proportions in differently sized embryos?

Selected Reading

1) Müller P, Rogers KW, Jordan BM, Lee JS, Robson D, Ramanathan S, Schier AF (2012). Differential diffusivity of Nodal and Lefty underlies a reaction-diffusion patterning system. Science, 336: 721-4.

2) Müller P, Schier AF (2011). Extracellular movement of signaling molecules. Dev Cell, 21: 145-58.

3) Müller P, Kuttenkeuler D, Gesellchen V, Zeidler MP, Boutros M (2005). Identification of JAK/STAT signaling components by genome-wide RNA interference. Nature, 436: 871-5.
(click to enlarge)
Model of an in vivo reaction-diffusion system studied in our lab. Nodal signals (blue) act over short ranges, whereas Lefty signals (red) act over long ranges to block Nodal signaling. The interplay between these short- and long-range signals is crucial for proper development, but we know little about the mechanisms that regulate the distribution and reception of Nodal and Lefty or how this system allows robust patterning.

(click to enlarge)
Mathematical simulations of the beautiful self-organizing patterns that reaction-diffusion systems involving short-range activators and long-range inhibitors can generate. Short-range activators and long-range inhibitors are frequently utilized during development, but the biophysical properties of these signaling networks in living embryos are currently largely unknown.