About this role
PhD Position: Structural Analysis of Adherens Junctions in Drosophila by Cryo-Electron Microscopy Institute: Buchmann Institute for Molecular Life Sciences (BMLS), Frankfurt Funding: DFG Research Training Group iMOL (GRK 2566) Position: E13 TV-G-U, 65 %, 36 months PI: Prof. Dr. Achilleas Frangakis Professor for Electron Microscopy and Tomography · Spokesperson iMOL Research Training Group Scientific Background Adherens junctions (AJs) are cell-cell adhesion structures fundamental to tissue integrity and morphogenesis.They couple neighbouring cells mechanically through cadherin-based extracellular interactions and link intracellularly to the actin and microtubule cytoskeleton. Despite their central role in development and disease, the molecular architecture of AJs in their native cellular context remains poorly understood. In this project, we exploit a unique opportunity offered by Drosophila melanogaster dorsal closure (DC) - one of the best-characterised morphogenetic processes in animal development. During DC, the spatial dimension along the closing front can be directly equated to the temporal dimension, converting otherwise static structural techniques into a four-dimensional (4D) analytical platform. This allows us to study the build-up, remodelling, and turnover of AJs across developmental time using volume electron microscopy (vEM) and cryo-ET. Figure 1. Correlative approach for studying adherens junctions during dorsal closure. (a) Pre-freezing light microscopy time-lapse (scale bar 20 µm). (b) Serial TEM 3D reconstruction showing amnioserosa cells (green), leading-edge cells (brown), and filopodia/TNT-like structures (orange arrows) at the junctional interface. The candidate will use CLEM, serial section volume EM, and cryo-ET to resolve the molecular architecture of adherens junctions during dorsal closure, across five specific objectives: Visualise and resolve the extracellular and intracellular architecture of AJs during dorsal closure by serial section TEM and FIB-SEM Investigate cytoskeletal interactions with AJs, focusing on the mechanism by which depolymerising microtubule plus-ends attach to cell-cell junctions Study structural modifications in AJ-deficient zebra mutant embryos and elucidate the mechanism of developmental rescue Develop algorithms for MD simulations based on low-resolution cryo-ET maps, extending beyond traditional flexible fitting methods Estimate biophysical properties of the junctions and compare them with macroscale measurements such as laser cutting Required Excellent MSc in molecular biology, biochemistry, structural biology, biophysics, or related discipline Strong interest in electron and/or light microscopy Experience with cell biological, biochemical, or biophysical methods Very good written and spoken English Motivation for interdisciplinary work Advantageous Experience with cryo-ET, FIB-SEM, or volume electron microscopy Background in structural biology or molecular dynamics simulations Familiarity with Drosophila genetics and embryo handling Programming skills (Python, MATLAB) Experience with image segmentation or quantitative analysis Motivated candidates are encouraged to familiarise themselves with recent work from the Frangakis group. A good entry point is Moser et al. (Nature Communications 2025) and Birtasu et al. (Kidney International 2025), which use the same cryo-FIB-milling and cryo-ET toolkit applied in this project. The position is embedded in the DFG Research Training Group iMOL (GRK 2566), providing a structured PhD programme including lectures, workshops, retreats, and an annual Winter School. You will have access to state-of-the-art cryo-electron microscopes and FIB-SEM at FCAM and FCEM Frankfurt. The position is funded at E13 TV-G-U, 65 %, for 36 months.