Simple roundworm may hold the key to understanding cell death processes

A biologist at The University of Texas at Arlington hopes that a simple roundworm might hold the key to understanding novel cell death processes. Such knowledge could lead to improved therapies to treat a variety of conditions in humans, including cancer and neurological injuries.

Piya Ghose, assistant professor of biology, recently received a five-year grant from the National Institutes of Health to study which genes contribute to the death of complex cells. The grant is a Maximizing Investigator's Research Award Outstanding Investigator Grant from the National Institutes of Health's (NIH) National Institute of General Medical Sciences. The project is titled "In Vivo Genetic Analysis of Compartmentalized Cell Elimination."

"Sometimes cells have to die, and this takes place through killing programs dictated by our genes," Ghose said. "This programmed cell death is critical for our normal function, getting rid of cells that are harmful and making sure we have just the right number of cells we need."

Many cells have highly complicated structures, with long projections or extensions. One example is brain nerve cells, which have long extensions from their main body to help relay information. Scientists do not presently entirely understand how these cells with complicated structures die.

"When we are born, we have way more nerve cells in the brain than we need, and in fact half of them are killed off," Ghose said. "As the brain develops and functions, nerve cell connections are made, but also lost through trimming or pruning of the extensions. Aside from when we grow and develop, cell death occurs under pathological neurodegenerative conditions as well as following injury."

Ghose is working with nematodes, a type of roundworm, because many of the genes found in the nematode C. elegans have similar counterparts in humans, making them useful models to study human disease. The worm holds a wealth of information on how cells with complicated shapes like neurons die.

"Once I started working with the nematode, I sort of fell in love with it and appreciated it as a great system to use to study different questions," Ghose said. "Worms are one of the easier systems to work with. I've been a worm enthusiast for many, many years."

During her postdoctoral work, Ghose discovered a cell-killing phenomenon in C. elegans, first observed in the worm's tail, that had never been described before. In two types of cells with complicated structures, one being a neuron, she observed that the dying cell segmented into three compartments, each dying in a very distinct way. Ghose named this novel form of cell death "Compartmentalized Cell Elimination," or CCE.

"Since we see CCE in two different cell types in the worm and because many of the genes we've identified as important for CCE have human counterparts, there is a high probability that CCE occurs in humans as well," Ghose said. "The long-term hope is to develop targeted therapies for neurodevelopmental and neurodegenerative disorders and injury as well as cancer."

With the NIH grant, Ghose and her team will aim to unravel how these genes play a role in CCE and how CCE takes place, thus learning more about how complex cells die.

"If we can better understand what genes are involved in this novel program of cell death, we'll have a better take genetically on how complex cells in general die," she said. "Long-term, that could allow us to develop targeted therapies to treat these conditions by turning on and off certain genes."

Clay Clark, professor and chair of the UTA Department of Biology, said that Ghose's project "has exciting possibilities for advancing our ability to better understand cancer and disease, and for finding more effective ways to treat them."

"Dr. Ghose and her team are making great contributions to UTA's mission to be a leader in cancer research," Clark said. "This NIH award is the latest testimony of the excellence of her work and highlights the outstanding quality of the research being conducted in the Department of Biology."

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