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
- prof. Mgr. Vítězslav Bryja, Ph.D.
- Mgr. Jakub Harnoš, Ph.D.
- Mgr. Marek Kravec, Ph.D.
- Other MU Faculty/Unit
-
Central European Institute of Technology
- prof. RNDr. Robert Vácha, PhD.
- Tereza Gerguri
- Mgr. Alžběta Türková
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
2021
2020
-
Effect of membrane composition on DivIVA-membrane interaction.
BBA Biomembranes, year: 2020, volume: 1862, edition: 8, DOI
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Magainin 2 and PGLa in Bacterial Membrane Mimics II: Membrane Fusion and Sponge Phase Formation.
Biophysical Journal, year: 2020, volume: 118, edition: 3, DOI
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Yeast Spt6 Reads Multiple Phosphorylation Patterns of RNA Polymerase II C-Terminal Domain In Vitro
Journal of Molecular Biology, year: 2020, volume: 432, edition: 14, DOI
2019
2018
2017
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The connections of Wnt pathway components with cell cycle and centrosome: side effects or a hidden logic?
Critical Reviews in Biochemistry and Molecular Biology, year: 2017, volume: 52, edition: 6, DOI
-
The N-Terminal Part of the Dishevelled DEP Domain Is Required for Wnt/beta-Catenin Signaling in Mammalian Cells
Molecular and cellular biology, year: 2017, volume: 37, edition: 18, DOI