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Project information
Computational chemistry for Wnt signaling pathway

Project Identification
MUNI/G/1100/2016
Project Period
3/2017 - 12/2019
Investor / Pogramme / Project type
Masaryk University
  • Grant Agency of Masaryk University
  • INTERDISCIPLINARY - Interdisciplinary research projects
MU Faculty or unit
Faculty of Science
Other MU Faculty/Unit
Central European Institute of Technology

Wnt signaling pathway is a one of the most important signaling routes required for the communication among cells, which is crucial for tissue homeostasis. Despite the clear (patho-)physiological relevance of Wnt signaling pathway, the molecular mechanisms regulating the pathway are poorly known. The proposed project will address several long standing questions related to the molecular regulation of Wnt signal transduction in the cytoplasm. We will focus on the key cytoplasmic protein regulator – Dishevelled (DVL) – which is heavily phosphorylated in response to Wnt stimuli and which, by unknown mechanisms, regulates strength and direction of downstream signaling. Specifically, we will use the combination of experimental data and computational modelling to get insight into the molecular mechanisms, which control cell membrane recruitment of human DVL, and which regulate DVL conformation. Experiments from Bryja´s group focused on identification of the post-translational modifications (mainly phosphorylations) and intermolecular interactions of DVL in various functional states will create a basis for in silico modelling. Computer simulations from Vacha’s team will complement the experiment with molecular details on stability and mechanism of individual conformations. The in silico results will then in turn guide further experiments, which will confirm/not confirm the computer predictions. We believe that the combined approach will overcome the current limits of the individual methods and together we will provide the mechanism how DVL performs its multiple functions.

Publications

Total number of publications: 8

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2017

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