Systems biology of vertebrate development and disease

Patrick Müller

Portrait Patrick Mueller flipped
  • 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 question 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? What factors regulate the diffusion and stability of signals?

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 might such systems function in living embryos? 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 during development 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 molecules, signal transducers, and transcription factors lead to disease onset, and how can treatment therapies be tailored to patients?

 

  • Fig1 Patrick Mueller
    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.

  • Fig2 Patrick Mueller
    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.



 

 

Available PhD Projects

Project 1: Analysis and control of multicellular self-organization.

Project 2: Modeling tumorigenesis in zebrafish to identify novel cancer therapies.

Selected Reading

1) 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.

2) Donovan P, Dubey OA, Kallioinen S, Rogers KW, Muehlethaler K, Müller P, Rimoldi D, Constam DB (2017). Paracrine Activin-A signaling promotes melanoma growth and metastasis through immune evasion. J Invest Dermatol 137:2578-87.

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.