The systems biochemistry of polarized cytoskeletal morphogenesis

• Applicant: Dr. Peter Bieling
• Subject Area: Biochemistry ; Biophysics ; Cell Biology
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 399893760

Living cells organize their interior in a non-random, polarized manner to carry out specialized biological functions. Cell polarity arises from a complex interplay between the plasma membrane, associated proteins and cytoplasmic molecules. In eukaryotic cells, symmetry is in most cases initially broken at the level of membrane-bound molecules such as phosphatidylinositol lipids and Rho-type GTPases. These conserved signaling hubs synergistically control cell morphogenesis and movement through the actin cytoskeleton. While many of the components of these intimately linked systems have been defined, very little is known about the biochemical mechanisms underlying cell polarity and shape changes. Instead of studying intracellular pattern formation and actin assembly in the cellular environment, I want to establish the minimal requirements for polarized cell morphogenesis through bottom-up reconstitution from purified components. While this process is very complex and highly regulated in living cells, we have reached a point in the field where a number of select, pertinent questions can be addressed in such a manner. Specifically, I want to understand (i) how membrane-associated signaling systems self-organize into macroscopic spatial patterns and (ii) how membrane polarity can be harnessed by the actin cytoskeleton to construct distinct structures at opposing ends of the cell. To this aim, I will combine multiprotein reconstitution on artificial membranes with advanced fluorescence imaging techniques and employ synthetic biology methods. As a whole, this work has the potential to advance our understanding of the mechanistic foundations of cell polarity and morphogenesis at the systems biochemistry level.

• DFG Programme: Research Grants