Bio

Eric van Leen is a PhD student in the lab of Dr. Yohanns Bellaïche at the Curie Institute in Paris. There he investigates the role of spindle orientation during morphogenesis in the pupal notum. Before starting his PhD, Eric obtained a Bachelor’s and Master’s degree at Utrecht University where he focused on Molecular Life Sciences. To complete the necessary training for his Master’s degree, he worked in multiple labs.

His first research experience was in microtubule polarity in C. elegans neurons in the labs of Prof. Dr. Casper Hoogenraad and Prof. Dr. Sander van den Heuvel at Utrecht University. Then he performed his second internship in the group of Prof. Dr. Robert Langer at the Massachusetts Institute of Technology, where he investigated the molecular mechanisms of cell membrane repair after plasma membrane disruption. Lastly, he was a summer student in the lab of Dr. Andrew Carter at the Laboratory of Molecular Biology, where he looked at the interaction between cargo adapters and dynein-dynactin.

Project

The orientation of cell division along the interphase cell long axis, the century old Hertwig’s rule, has profound roles in tissue proliferation, morphogenesis, architecture and mechanics. In epithelial tissues, the shape of the interphase cell is influenced by cell adhesion, mechanical stress, neighbor topology, and planar polarity pathways. We have recently uncovered the mechanisms by which cells sense and memorize their interphase shape. We found that in Drosophila epithelia, tricellular junctions (TCJ) localize microtubule force generators, orienting cell division via the Dynein associated protein Mud (NuMa in vertebrates) independently of the classical Pins/Gai pathway. Moreover, as cells round up during mitosis, TCJs serve as spatial landmarks, encoding information about interphase cell shape anisotropy to orient division in the rounded mitotic cells. Finally, experimental and simulation data show that shape and mechanical strain sensing by the TCJ distribution emerge from a general geometric property of TCJ distribution in epithelial tissues. Our work reveals that, in addition to their function as epithelial barrier structures, TCJs serve as polarity cues promoting geometry and mechanical sensing in epithelial tissues (Bosveld et al., 2016). This work raised very important questions in the field of tissue morphogenesis and proliferation such as: How is Mud localized to the TCJ and what is the consequence of loss of Mud at TCJs on tissue dynamics and morphogenesis? The Ph.D. project aims to address these two fundamental questions using a combination of time-lapse microscopy, genetics and innovative quantitative tools. This work should provide a better understanding of the mechanisms underlying tissue development and homeostasis since spindle orientation plays a critical role in tissue dynamics and cell fate specification.