302: A Very Significant Number

Assistant Professor of Biology Gal Haspel

Gaining New Neural Knowledge From a Tiny Creature

Caenorhabditis elegans, or “C. elegans” to close friends like Assistant Professor of Biology Gal Haspel, is not very big in size. This common worm grows to a maximum of one millimeter in length as an adult and, incidentally, lives for about two weeks. But C. elegans is hugely significant when it comes to gaining new biological knowledge — information that could help with recovery from neurological damage in humans, including spinal cord injuries.

Haspel, who bills his laboratory as NJIT’s “worm lab,” joined the Federated Department of Biological Sciences in 2013. His background includes work with C. elegans at Harvard Medical School and the National Institutes of Health. On the first day of introducing C. elegans to his

Caenorhabditis elegans

Just one millimeter in length when fully grown, the tiny worm Caenorhabditis elegans is providing neurological information that could help humans recover from spinal cord injuries.

NJIT students in class, he says that he writes the number “302” on the board to emphasize its significance. It is the total number of neurons that C. elegans has, and this diminutive member of the nematode family is the only creature whose neuron structure has been so precisely quantified, and precisely labeled.

Interest in C. elegans is not new. Research that has yielded basic genetic insights and thus far three Nobel Prizes was under way in the 1960s. But as Haspel explains, it has only been since the turn of the 21st century that he and other investigators have had the tools to determine the relationship between specific neurons and particular movements in living tissue. These tools include optogenetics to both record and control the activity of neurons using light, and serial block-face scanning electron microscopy to generate high-resolution three-dimensional images from minute biological samples.

Haspel recently co-authored an article for Bioscience titled “Neurobiology of Caenorhabditis elegans Locomotion: Where Do We Stand?” In addition to his NJIT faculty affiliation, the article identifies Haspel as a neuroethologist — a scientist who investigates how neural systems underlie natural behavior. And the behavior that Haspel is studying in his lab at NJIT with the help of C. elegans encompasses the neural basis of locomotion, and the underlying connectivity, activity and recovery from injury.

Taking a hard look

While the Bioscience article summarizes the considerable amount of information that is on record regarding movement, particularly forward- and backward-directed motion during crawling and swimming, the main conclusion is that much remains to be discovered. “We took a hard look at what has been learned to date, and the bottom line is that there are significant gaps in our knowledge,” Haspel says.

“We’re knowledgeable about many details, about all the different parts in the creature’s locomotion system. But how these parts cooperate to produce movement is still not clear.”

Researchers do have what Haspel calls a working anatomical “wiring diagram” for C. elegans. However, it is not a comprehensive map of functionality. There are important questions to be answered about how certain neurons are connected, and how they function with respect to their role in specific movements.

Current C. elegans knowledge also has a “variability gap.” Is the current connectivity model really typical of the organism? It’s a question that Haspel intends to investigate in the course of his research.

A bigger picture

The understanding to be gained from experimentation with the simple neural structure of C. elegans has implications for expanding our neurophysiological knowledge of creatures that are much more complex, up to the level of humans. One investigative avenue that Haspel is following involves the idea that the imperative to recover from injury has been a key factor in the evolution of the vertebrate nervous system, that survival has required an innate capacity to move as effectively as possible after an injury.

Haspel is investigating this concept with the support of a $200,000 exploratory grant from the New Jersey Commission on Spinal Cord Research. The simplicity of the C. elegans nervous system allows research in this area to be conducted through the manipulation of individual neurons and associated muscle tissue.

The nervous system will “try to do something” to regain the ability to support movement following injury, Haspel says. Although it may not be sufficient, and the damage may even be fatal, there will be a natural attempt at recovery. The unknowns in this process include ascertaining what happens when neural impulses are “rerouted” during recovery.

After healing, when a connection that has been lost is restored, it may be that the rerouted connection becomes the primary channel and that the former one is not needed. Or the system may revert to its original state and any new connections become inoperative. Another possibility is that something will happen that’s “in between,” with a conflict between the old and new neural routes that slows or prevents recovery. Increasing our understanding of these neural possibilities with the help of C. elegans could provide new insights into our potential to heal from neurological injuries and help to improve treatment and therapy.

The best place to be

Commenting on his decision to join the Federated Department of Biological Sciences, Haspel says that it’s “the best place to be” for someone in his field. “It’s the best biology department I’ve seen,” he adds without reservation.

Haspel cites the complementary interests of many of his NJIT colleagues in animal behavior at all levels, from the cellular research that he’s pursuing to swarm activity and the ecology of animal populations in their respective environments. But in addition to the benefits of being part of the 11-member, very collegial NJIT contingent in the department, Haspel emphasizes the advantages of being affiliated with Rutgers, which gives students access to opportunities for study across a broad biological spectrum. “It’s a great program, and there’s a lot of good science being done in Newark.”