Analysis of neuronal remodeling during transitions between reproductive live cycle and dauer stage in C. elegans

• Applicants: Professor Dr. Thomas Dandekar; Professor Dr. Philip Kollmannsberger; Professor Dr. Christian Stigloher
• Subject Area: Developmental Biology ; Bioinformatics and Theoretical Biology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 495531075

To understand how changes in neuronal signaling affect behavior, the molecular details of neuronal communication must be combined with neuronal connectivity. An ideal model organism to study how wiring and function are connected is the nematode C. elegans. Its nervous system is much simpler compared to vertebrates or insects, but still complex enough to exhibit a range of interesting and functionally distinct motor behavior. On top of that, nematodes can undergo a unique and reversible developmental transition to the dauer stage that involves radical changes in morphology and behavior. We aim to address the question how neuronal remodeling during developmental transitions in nematodes affects function. Solving this challenge requires i) high-resolution ultrastructural imaging to identify differences in the neuronal system between dauer and adult stages, ii) a detailed functional network model of the neuronal system on the cellular and systems level, and iii) quantitative behavioral experiments to validate the predicted network output and to test different hypotheses. We acquired a full FIB-SEM (Focused Ion Beam – Scanning Electron Microscopy) dataset of the central nervous system and anterior sensory organs of C. elegans dauer in collaboration with the Schwab group at EMBL Heidelberg. We then manually traced and annotated the connectome in collaboration with the group of Dr. Mei Zhen at the University of Toronto. In further preparator work for the project, we developed automated image analysis tools to quantify the synaptic vesicle pool in electron tomograms, and trained artificial neural networks to predict cell boundaries and nuclei in FIB-SEM data. We will refine and combine these tools with algorithms to quantify cell and network morphology based on work by P. Kollmannsberger and will then apply them to newly acquired image datasets. We will then adapt and use network modeling tools developed by the Dandekar group to quantitatively predict differences in motor behavior between dauer larvae and stages of the reproductive life cycle based on these datasets. Finally, we will explore the model predictions experimentally using a behavioral video-microscopy setup. Understanding how the nematode nervous system changes during the rapid transition between normal and dauer stages might answer many unsolved questions of neuronal development and plasticity and could lead to a better understanding of biological strategies to survive adverse environmental conditions in general.

• DFG Programme: Research Grants