The C. elegans locomotion nervous system: an integrated multi-disciplinary approach

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C. elegans is one of the simplest creatures of the animal kingdom. With a mapped genome and the only mapped neural circuitry, this organism offers a first tangible opportunity to understand an entire living, behaving and learning system bottom-up and top-down. As such, it offers great promise to systems biologists, neuroscientists and roboticists alike. Despite its relative simplicity, C. elegans possesses many of the functions that are attributed to higher level organisms, including feeding, mating, complex sensory abilities, memory and learning. Can we understand the underlying engineering designs that allow this tiny nematode to survive and flourish? What insight can we gain into universal principles that give rise to adaptive and robust life-forms or to the unique architecture of its nervous system? Meeting this challenge requires a large multi-disciplinary effort, combining insight and expertise from biology, physics, engineering and computer science.The proposed research focuses on achieving a step change in our understanding of the C. elegans locomotion system and its neural control. At the modelling level, current theoretical models of the locomotion subsystem of C. elegans rely on genomic data, the known neural circuitry, limited behavioural and electrophysiological experiments on C. elegans and knowledge from other related species. All in all the knowledge base for this modelling feat is very incomplete and hence all models to date make a large number of unconfirmed assumptions. Very fundamental questions, such as whether the locomotion system relies on endogenous control in the form of central pattern generation, have recently been debated. These questions can be addressed in mathematical and simulation models; however, the physical environment (pressure, friction, sensory inputs) may be too complex to incorporate reliably in a model. I propose to construct robotic models of the nematode, incorporating alternative predicted models of neuronal circuits and to test them under a variety of physical conditions, mimicking behavioural experiments on the biological worm. This project involves three levels of investigation: First, systematic behavioural studies of the locomotion of the worm; second, the construction, analysis and simulation of detailed neurocomputational models of the locomotion system; and third, the construction of robotic models and their testing.At the technological level, probing the activity of C. elegans neurons and muscles has eluded electrophysiogists due to the mechanical properties of the worm. Hence, despite some progress, it is remarkably difficult to confirm or further develop models of neuronal subsystems such as the locomotion subsystem. At the same time, C. elegans is transparent and hence amenable to fluorescence recordings. Efforts are underway to develop voltage-sensitive dyes for sensory neurons, but to date, C. elegans neurons or muscle cells have not been fluorescently recorded from. I propose to develop molecular voltage probes to directly record the voltage-activity of C. elegans locomotion muscles. This effort builds on my preliminary work in which quantum dots (semiconductor nanoparticles) have been embedded in biological membranes. The next steps involve obtaining a voltage-response from these probes and embedding them in cells of living animals. The ability to monitor the voltage activity in behaving animals should lead to a step change in our understanding of the locomotion system in particular and the C. elegans motor system in general. Furthermore, implementation of this technology should constitute a major advance that extends much beyond the study of C. elegans to a wide range of scientific and industrial applications in both biological and bioinspired engineering domains.