Why C. elegans?
Caenorhabditis elegans is a 1 mm roundworm that has become an ideal model organism for studying the molecular mechanisms of learning and memory.
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Practical Advantages: Its small size, short life cycle (<3 days), and ease of cultivation make it highly suitable for laboratory research. Reproduction through self-fertilizing hermaphrodites supports both inbreeding and crossing with males.
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Genetic Tools: The genome has been fully mapped and sequenced, with thousands of mutants and RNAi constructs readily available.
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Biological Simplicity: The adult hermaphrodite consists of 959 cells (Sulston & Horvitz 1977; Sulston et al. 1983), including 302 neurons with a fully mapped connectome (White et al. 1986).
Despite this simplicity, C. elegans demonstrates short- and long-term non-associative learning, associative learning, and imprinting. Worms can habituate to mechanical and chemical stimuli and learn predictive cues such as odors, tastes, temperatures, and oxygen levels. In many cases, the underlying neural circuits have been at least partially described, and genetic tools are used to uncover the molecular and cellular mechanisms.
Overall Research Goals
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Uncover the mechanisms of learning and memory at the genetic, synaptic, neural circuit, and behavioural levels.
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Understand how genes and genetic variants linked to neuropsychiatric diseases, including Autism Spectrum Disorder, Parkinson’s disease, and Alzheimer’s, affect neuronal function and pathology.
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Explore how early life experiences, such as ethanol exposure (a model of Fetal Alcohol Spectrum Disorder), influence adult behaviour and morphology.
Primary Research Techniques
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Automated morphological and behavioural (phenomic) characterization of C. elegans using the Multi-worm Tracker (Sw et al., Nat. Methods)
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Conditional genetic knock-out, targeted rescue, and development of “humanized” C. elegans models with CRISPR genome editing
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Confocal and fluorescence microscopy of neurons and synapses
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Optogenetic manipulation of neural activity
Focus on Habituation
The Rankin Lab was the first to investigate learning and memory mechanisms in C. elegans, focusing on habituation, a simple but fundamental form of learning.
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What is habituation? Organisms cannot process every sensory input equally and must filter repetitive or irrelevant stimuli. Habituation is this filtering process (for review see Bozorgmehr et al., Front. Physiol.).
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Why does it matter? Habituation is found in all organisms, from paramecia to humans, and abnormalities are associated with multiple disorders such as ASD, schizophrenia, and Parkinson’s disease. Despite its simplicity and importance, the mechanisms remain poorly understood.
Broader Implications
While C. elegans is a simple organism, the molecular and neural processes uncovered in our lab have direct relevance to human health. The transparency, sequenced genome, and mapped connectome of C. elegans allow us to dissect learning and memory with unparalleled precision, and its short life cycle makes it an efficient system for modeling developmental experiences.
Importantly, many of the genes and pathways that regulate C. elegans behaviour are highly conserved in mammals, meaning discoveries in worms often reveal principles that translate directly to higher organisms, including humans. By identifying the genetic and neural mechanisms underlying behavioural plasticity, our research provides insights into the biological foundations of learning, memory, and neuropsychiatric disorders. This work lays the groundwork for understanding how genetic variants contribute to disease and may ultimately guide therapeutic strategies.
Current Directions
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Build a comprehensive understanding of habituation and its effects on ongoing behavior.
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Compare habituation with other forms of non-associative learning such as sensitization and dishabituation.
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Characterize the roles of genes and genetic variants implicated in Autism Spectrum Disorder, Parkinson’s disease, and Alzheimer’s to better understand their pathology.