Author: Andoni Mujika Amunarriz

Directors: Gorka Epelde Unanue (Vicomtech) Miguel Otaduy (University)

University: Universidad Rey Juan Carlos (URJC)

Date: 13.07.2018

Place: Madrid

Caenorhabditis elegans (C. elegans) is a roundworm that, thanks to its combination of biological simplicity and behavioural richness, offers an excellent opportunity for initial experimentation of many human diseases. To help researchers that work with this nematode, in this PhD thesis we implement several tools that enable the design of in silico experiments.   First we present two locomotion models for C. elegans. In the fi rst one, the contraction of the muscles is guided by the signals that come from the motor neurons. In the second model, the key is a simple locomotion control strategy that activates selected natural vibration modes of the worm. Together with force compensation for momentum conservation and an anisotropic friction model, we achieve locomotions that match qualitatively those of real-world worms.   Apart from the simulation of C. elegans itself, we model the stimuli that are applied within behavioural experiments and the stimuli that are generated in the interaction of the C. elegans with the environment. We model a wide range of different stimuli including the most common stimuli involved in behavioural assays: mechanosensation, thermosensation, chemosensation, galvanosensation, photosensation and proprioception.   For the de finition and visualisation of in silico behavioural experiments we present a suite of uni ed web-based Graphical User Interfaces (GUIs). The user-friendly features of these tools enable users to graphically interact with the system without requiring knowledge of domain-speci fic computer-science tools. Moreover, we present a novel XML-based behavioural experiment defi nition encoding format that facilitates exporting models, experiment de finitions and results, thereby facilitating reproducible and cross-platform execution of in silico C. elegans experiments
in other simulation environments. User survey data con rms the platform usability and functionality, and provides insights into future directions for web-based simulation GUIs of C. elegans and other living organisms.   Finally, a closed loop involving stimuli generation, a neuronal network (not a contribution of this PhD thesis) and the muscular simulation of the worm are presented. In this concluding test, C. elegans responds to chemical stimulus moving its head towards the attractant. When a Central Pattern Generator (CPG) is added, the worm crawls towards the source of the received stimuli.


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