Deciphering the role of actomyosin remodeling and mechanotransduction in sea urchin skeletogenesis

• Applicant: Professorin Yael Politi, Ph.D.
• Subject Area: Biophysics
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 524590563

Organisms across metazoans uptake minerals and build intricate structures that support and protect them; these biominerals constitute most of the fossil record of life on earth. Biominerals often have structural properties that are beyond the state of the art of manmade materials, which inspires the fabrication of biomimetic mineral structures. For all these reasons, how cells control mineral shape and properties is fascinating for developmental, cell and evolutionary biologists as well as for material scientists, yet, the molecular mechanisms that regulate biomineralization are far from clear. Multiple indications points to the actomyosin network's involvement in biomineralization in Eukaryotes, from calcifying and silicifying unicellular organisms to vertebrate bone and teeth development. The actomyosin network is an essential part of mechanosensing and mechanotransduction, the ability of cells to sense and respond to the mechanical properties of the extracellular environment. However, it is yet unknown which aspects of biomineralization require mechanosensing and mechanotransduction and which effector proteins participate in this process. The overall goal of this proposal is to decipher the roles of actomyosin remodeling and adhesion proteins in controlling mineral growth and shaping mineral morphology using sea urchin embryos and skeletogenic cell cultures as a model. We had already identified actomyosin remodeling and adhesion proteins that are key to sea urchin skeletogenesis and participate in bone formation and homeostasis, e.g. RhoA associated coil-coil Kinade (ROCK), CDC42 and Focal adhesion kinase (FAK). We will first identify the proteins regulated by ROCK, CDC42, FAK using proteomic and phospho-proteomic analyses and we will investigate their function in live sea urchin embryos. We will then utilize sea urchin skeletogenic cell cultures to conduct high spatio-temporal studies using advanced light and electron microscopy. We will study skeletal growth, morphology and molecular markers in control and under the perturbations of the abovementioned proteins to gain insight into the molecular control of biomineral deposition and growth. The complementary approaches and expertise of the three PIs will allow us to reveal the interactions between the actomyosin remodeling network and adhesion proteins, and how these interactions control the growth and the shape of the forming biomineral.

• DFG Programme: Research Grants
• International Connection: Israel
• International Co-Applicants: Professorin Smadar Ben-Tabou de-Leon, Ph.D.; Professor Haguy Wolfenson, Ph.D.