What a small, wiggling worm can teach us about cancer | The Queen’s Journal

Queens biologists study the genetics behind cell proliferation and what it can tell us about tumor formation and metastases.

Caenorhabditis elegans
Caenorhabditis elegans is a roundworm used to study developmental biology and neurobiology.

One would think that a transparent, tiny – about a millimeter long – organism could have a hard time catching anyone’s attention. The roundworm Caenorhabditis elegans (C. elegans), however, has been in the spotlight of biological research for decades. Researchers first proposed the worm as a model for studying evolutionary biology and neurobiology in the 1960s. In 1998 C. elegans became the first animal to have its genome fully sequenced, and even today, hundreds of laboratories dedicate time and resources to finding out more about the worm and how it can help us answer some of biology’s basic questions.

How does a single cell become a multicellular organism? What genes control cell division and cell movement? Ian Chin-Sang, a developmental biologist, has dedicated his career to asking these and similar questions. In his laboratory at the Department of Biology at Queen’s, he combines genetics, molecular biology, biochemistry and video microscopy techniques to study C. elegans and understand how animals – including humans – evolve.

C. elegans and humans share about 40 percent of the same genetic makeup – meaning that 40 percent of human genes are homologous or similar in structure to the worm’s DNA. On the other hand, roundworms are much simpler organisms with only about 1,000 cells, and their transparent bodies make it easy to observe them in detail, even at the single cell level.

Over the last few years, Dr. Chin-Sang and his team studied C. elegans to study cancer genes – those that can promote cell division in tumors and metastases. They have also studied tumor suppressor genes that prevent cells from multiplying. Mutations and genetic predispositions that block tumor suppressor genes can lead to cancer.

“We study how the worm evolves and apply this knowledge to understand what goes wrong during cell division that causes cancer,” explains Dr. Chin-Sang. “We are also interested in the mechanisms behind how tumor cells invade surrounding tissues and move to other sites and create new tumors. If we can block this mechanism, we can prevent metastases.”

Tapeworms do not develop cancer like humans. But they have tumor suppressor genes and are a good model for understanding what exactly happens when these genes are knocked out. In worms, as in humans, mutations in a tumor suppressor gene can lead to inappropriate cell division and movement, leading to premature death.

Dr. Chin-Sang’s team is particularly interested in the worm’s genetic correspondent for PTEN, a gene whose loss is involved in about 70 percent of prostate cancers and other types of tumors. Although humans and roundworms have obvious differences, what happens inside the cells of each organism is comparable.

“We think of the cell as a molecular machine that has to work properly. What happens if you change the components of the machine? That’s what we model in the laboratory. How that machine works in the worm is probably the same as it does in human cells, ”says Dr. Chin-Sang.

Scientists can manipulate C. elegansnuisances in all possible ways. Researchers can also use the worm to test drug candidates and see if they are effective in slowing cell division or cell movement. These experiments can ultimately guide scientists on which substances to test in more complex biological models and ultimately in humans.

Caenorhabditis elegans
The transparent body of one C. elegans is made of about 1,000 cells.

Current programs

In addition to studying cell division and its links to cancer, Dr. Chin-Sang’s team the cellular insulin signaling pathway. While insulin is best known for regulating blood sugar levels, worsening insulin signaling can lead to tumor development. Though C. elegans do not produce insulin, they have insulin-like molecules, and the molecular machinery that regulates them is very similar to the insulin signaling pathway found in human cells. The worm also has genes that can block such signaling, providing insight into what is happening to humans.

“This can be very important in designing new drugs,” says Dr. Chin-Sang. This research program is funded by the Canadian Institutes of Health Research (CIHR).

Another ongoing program is funded by the Natural Sciences and Engineering Research Council of Canada (NSERC) and aims to clarify how embryonic cells change their shape and move to fold into three-dimensional shapes. This process is called “morphogenesis”, and it is an important aspect of development, as it is necessary to give organs and tissues their three-dimensional shapes. The team is working to identify and characterize genes and proteins that regulate this process.

As a developmental biologist, Dr. strives Chin-Sang after answering basic scientific questions and is not always sure, especially not in the early stages of a research project, of the possible applications of the knowledge that is being built. But being open to the unexpected pays off – who would have thought that a small roundworm could teach us so much about our own health?

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