Systems biology of vertebrate development and disease

Patrick Müller

mueller Portrait 18
  • PhD at the MPI for Biophysical Chemistry, 2004-2007
  • Postdoctoral fellow and research associate at Harvard University, 2007-2013
  • Emmy-Noether research group leader, MPI for Developmental Biology, 2013
  • Max Planck research group leader at the FML since 2014

Research Interest

My group studies how the interplay between signaling molecules controls development and disease. We combine genetic, biophysical, and theoretical approaches to address these questions in vertebrate model systems (zebrafish, mouse embryonic stem cells, and patient-derived cancer cells). Our research focuses on four areas:

1) 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?

2) 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 do signaling systems concertedly coordinate proper patterning?

3) 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 to establish the correct tissue proportions in differently sized embryos?

4) Aberrant signaling in disease: Signaling pathways that control embryogenesis are frequently deregulated in human cancers. How do acquired mutations in signaling pathway components lead to disease onset, and how can treatment therapies be tailored to patients?

       

  • Mueller IMPRS webpage 2018
    click to enlarge

Nodal and BMP orchestrate the patterning of germ layers and the dorsal/ventral axis (Rogers and Müller, Dev Biol 2018). (a) Nodal induces mesendoderm, its own expression, and its inhibitor Lefty. BMP induces ventral fates and is repressed by its inhibitor Chordin. (b) Binding of Nodal and BMP to type I and type II serine/threonine kinase receptors induces phosphorylation of cytoplasmic Smad proteins, which translocate to the nucleus and associate with transcription factors to activate target gene expression. (c) During zebrafish embryogenesis, lefty and nodal are expressed in the embryonic margin, patterning mesendoderm. (d) bmp is expressed in a ventrally peaking gradient along the dorsal-ventral axis, and chordin is expressed dorsally.



 

 

Available PhD Projects

Analysis and control of signaling systems during early vertebrate development.

Selected Reading

1) Almuedo-Castillo M, Bläßle A, Mörsdorf D, Marcon L, Soh GH, et al. (2018). Scale-invariant patterning by size-dependent inhibition of Nodal signalling. Nature Cell Biology 20:1032-1042.

2) Pomreinke AP, Soh GH, Rogers KW, Bergmann JK, Bläßle AJ, Müller P (2017). Dynamics of BMP signaling and distribution during zebrafish dorsal-ventral patterning. eLife 6:e25861.

3) Marcon L, Diego X, Sharpe J, Müller P (2016). High-throughput mathematical analysis identifies Turing networks for patterning with equally diffusing signals. eLife 5:e14022.