Dynamic microvilli and nanometric cellular 3D printing

How shape is defined in nature is a fundamental question in biology. Cell-to-cell signalling and collective cellular behaviour explain how shapes are forming at the larger scale of tissues and embryos. Likewise, ultrastructural approaches reveal shapes at the minute scale of molecules and their complexes. Very little, however, is known about the question how shape is defined in the intermediate scale of individual cells. To bridge this knowledge gap, this research proposal aims to advance research into the question how individual cells generate shapes at the micro-to nanometric scale. The project takes advantage of a unique cell type in marine bristle worms that undergoes programmed changes in its cell surface to produce and sculpt chitinous bristles that are also referred to as chaetae. Earlier work in the lab has shown that these chitinous bristles are produced in a cellular process that seems to parallel modern 3D-printers: starting with the tip, the bristle is gradually produced by chitin polymerisation at the surface of the biosynthetic cell, while the surface itself changes its shape over time in a stereotypical manner. A central role in this process is thought to be played by cell protrusions that extend and retract while synthesising the chitin matrix. The reproducibility of bristle formation predicts that dedicated molecular factors are involved in the extension and retraction of cell protrusions. In this project, we will test this hypothesis by investigating a first molecular factor that our work indicates to be involved in modulating the growth of the involved cellular protrusions, and thus impact on shape formation on the cellular size scale. We will test this idea by modulating the function of this gene, and score the impact of these functional changes on the geometry of the resulting bristle. Our work will combine reverse genetic tools with advanced technologies such as live video imaging at the level of super-resolution microscopy. We expect that the results of our work will help to shed first light on the fundamental genetic programme of shape formation, and also provide possible links to similar cellular geometries, as they occur in vertebrate development and disease.