Phos­MOrg

Project description:

Life of all organisms including ourselves critically depends on proteins and other biomolecules. Their modification by addition or removal of phosphates (phosphorylation/dephosphorylation) constitutes an important means for cells to regulate processes as vital as growth, division or morphogenesis (Fig. 1). Phosphomodifications are also crucial for synthesis of complex biominerals including highly ordered silicate skeletons of diatoms. Phosphorylation by dedicated enzymes (kinases) can alter the charge or conformation of the modified protein eventually, changing its biological activity. Therefore, kinases represent molecular ‘on/off’ switches that orchestrate chemical signals with proper cellular behaviour. Accordingly, improper phosphorylation due to kinase defects can lead to severe human diseases including cancer, neuropathies or chronic inflammation. To study phosphotransfer at the molecular level and better understand how phosphorylation controls biological output (intracellular signalling, morphogenesis of complex biological patterns, PhosMOrg has teamed-up CINSaT members with interdisciplinary expertise in kinase biology (Herberg, Müller, Schaffrath), nanochemistry (Fuhrmann-Lieker) and biomolecular modelling (Garcia). Using a unique combination of in vivo, in vitro and in silico methods, PhosMOrg aims to:

 

  • study phosphate transfer from the donor ATP to target molecules
  • determine the molecular mechanisms of protein kinase regulation
  • model how phosphorylation affects protein conformation and function
  • investigate how phosphorylation instructs cell shape and polarity
  • examine how phosphotransfer controls RNA modification and gene expression 
  • study how phosphorylation allows biomimetic design of nano-objects