The nematode C. elegans

The roundworm Caenorhabditis elegans is an organism that is used to systematically understand neural circuits and behavior. C. elegans has been used to discover different sensory pathways and study axon regeneration at a single neuron level. C. elegans have a comprehensive connectivity map containing around 302 neurons and 7000 synapses.

C. elegans are an exceptional model for studying biological processes due to several reasons. Firstly, they have a three-day lifecycle which is useful for studying aging as they pass through distinct phases of life that can be observed both physiologically and genetically. Secondly, C. elegans are transparent which enables microscopy and use of laser surgery as all 959 cells in their body are accessible. Thirdly, they are genetically and molecularly tractable with multiple distinct techniques available for examining and altering their biology.

Some interesting facts about C. elegans are they hold the distinction of being the first multicellular organism to have its entire genome sequenced. Additionally, C. elegans are a type of non-parasitic free-living nematode that can be found everywhere, and they are approximately 1 mm long. They are abundant in microbe-rich environments, such as decomposing fruits and stems. Another fun fact is C. elegans have been sent into space multiple times to study the impact of microgravity on aging and muscle degeneration.

There are databases that display the anatomical features of C. elegans and their cells. Visit wormbase, wormatlas, or wormwiring for more information about C. elegans

Neuroregeneration

The absence of an effective cure for central nervous system injuries and neurodegenerative diseases is an outstanding and costly deficiency in modern medicine. A fundamental barrier to recovering function is weak central axon regeneration, which is also strongly impeded by scarring at the injury site. One exciting discovery with profound neurotherapeutic implications is a robust regeneration by mammalian central axons following a “conditioning” lesion. Identifying critical components of lesion conditioning pathways would represent a key step toward successfully treating nervous system injuries and multiple neurodegenerative diseases, improving the quality of life for many people. Unfortunately, lesion conditioning has been studied in vertebrates for over 30 years without a comprehensive understanding.

We developed a model for axon regeneration in C. elegans that exhibits a lesion conditioning effect (Chung, et al. PNAS 2016). There are many genetic and phenotypic similarities with mammalian lesion-conditioned regeneration, indicating that they are mediated by conserved regeneration pathways and cellular mechanisms. Our form of regeneration is a novel model for mammalian lesion-conditioned regeneration, allowing us to leverage many of the worm’s advantages to rapidly study lesion conditioning

Cooling stage for easy and strong worm immobilization

We developed a cooling device that can easily immobilize large populations of C. elegans on their original plates with minimal user effort. You simply place your plate on the stage and all worms on the plate are cooled and immobilized. We quantified worm movement at different temperatures. Surprisingly, we found that warmer temperatures, like 6℃, can immobilize worms much better than colder temperatures near freezing. With 6℃ cooling, we were able to strongly immobilize worms for imaging.

We measured time spent on an imaging experiment, using either chemical or cooling immobilization. Chemical methods involve a lot of time processing animals and slides. Cooling saves at least 98% of that time. Cooling also allows us to manipulate worms on the plate while they are immobilized, which could be very useful for screening.

Optics

Improved imaging of C. elegans is crucial to fully understanding the complex structure of neurons. We focus on improving the quality of our microscope images by decreasing stray light. Often this light comes from the bright cell body and obscures thinner and dimmer neurites nearby. We can improve imaging through several routes, including improvements in hardware, feedback-mediated image acquisition, and image postprocessing. Techniques include targeted illumination microscopy, scanning illumination microscopy, and modeling of the stray light distribution.