Transferring decade-old live worms frozen in liquid nitrogen with a U-Haul truck may seem a little strange, but it is all part of the research happening in a UCSB lab that may help scientists understand how cells work.
Joel Rothman, professor of molecular, cellular and developmental biology, published his lab’s findings concerning this particular worm in the May issue of Developmental Cell, an academic journal dedicated to the topic. His research shows that a rare mutant of this worm has a genetic misconfiguration that causes its cells to fuse together uncontrollably. Studying this defect is important because cancers in humans sometimes rely on the process of cell fusion to spread throughout the body, and the results of Rothman’s research may have implications in human cancer treatments sometime in the future. By combining his findings with other recent developments in the field, Rothman has discovered that a specific gene — previously thought to be unrelated to cell fusion — is responsible for keeping cells from merging too rapidly.
The worm that is the subject of Rothman’s study is a nematode known as C. elegans. Rothman said this organism is a good choice for cellular research because it is only about 1 millimeter long, easily obtainable, and reproduces very rapidly, making genetic testing easier. The results are significant for humans because the worms and humans share the same basic “genetic toolkit” that makes fundamental cell functions work, Rothman said.
“These worms have been very attractive models for lots of biomedical problems,” Rothman said. “The reason that they are such an attractive organism is that you can ask questions of much greater depth and breadth than you can in a human or even a mouse. Our ability to manipulate the genetics to discover how the genes control the normal process far exceeds what we can do with mammals.”
Rothman directed a research lab about 12 years ago at the Univ. of Wisconsin-Madison where one of his researchers, Ivan Moskowitz, discovered a nematode in the lab that had a naturally occurring genetic defect that caused its cells to merge together into larger cells. This is not healthy for the worm, Rothman said, but it interested researchers because cell fusion is not a very well understood topic, and knowing more about it may contribute to progress in fields such as cancer research.
“When you get down to the basics of how cells work, how they interact with one another, how they control their normal states, then studying these worms is immediately applicable to understanding how humans work,” Rothman said.
At the time, Rothman didn’t have enough basic information to study the genetically defective worm, so he froze it in liquid nitrogen, which is extremely cold and allows the animals to be stored in suspended animation for many years. Once the worm is carefully removed from the liquid, it thaws out and continues to live as if it were never frozen, Rothman said.
After Rothman moved his lab to UCSB in a U-Haul truck, he thawed his extraordinary worms.
“It was a rare mutant — we didn’t want to lose it,” Rothman said. “We were the only lab in the world that had it. It sat in the freezer until about three years ago. When [a specific gene] was discovered, we realized we had a way to analyze this mutant.”
That particular gene, called EFF1, causes cells to normally fuse together in animals, a process that occurs in muscles and bones and is not harmful. Problems arise when another gene, FUS1, does not do its job to regulate that cell fusion.
Rothman’s defective worms are missing this FUS1 restraint gene, so their cells fuse together unusually quickly. Kenji Kontani, a former researcher in Rothman’s lab, carried out experiments to verify the link between the gene and the rapid cell fusion. Some cancer cells are also known to fuse as they spread through the body, so this genetic research may soon prove useful to cancer researchers.
“The important part of cancer that makes it deadly is that the cancer can change from just being rapidly dividing to becoming metastatic, meaning that it can migrate throughout the body and populate various parts of the body,” Rothman said. “For tumors to become metastatic, there are lots of mechanisms: genetic changes in the tumor cell can cause it; fusion of the tumor cell with another cell that has the ability to move around can also lead to metastasis.”
By controlling these fusion-regulating genes, Rothman said it might be possible to formulate new cancer treatments in the future.