Model organisms are widely used in biology research to understand how fundamental biological processes occur in all animals, including humans. The nematode C. elegans is one of the foremost model organisms, and has been used for groundbreaking insights in multiple areas of biology. C. elegans has many advantages as an experimental system, including powerful genetic approaches, but it lacks an essential tool: there are no C. elegans cell lines. Cell lines are cells that have been isolated from the animal and are able to continuously divide in a tissue culture system. C. elegans cell lines would allow for many experimental approaches that cannot be performed with the whole animal, including biochemical experiments with a homogeneous cell population, RNAi-based gene inactivation screens for cellular defects, and small molecule screens for bioactive compounds that modulate molecular pathways. The cell lines would be available for use by hundreds of laboratories to extend our knowledge of basic processes in a wide array of biological areas. This project seeks to isolate C. elegans cell lines from stem cells of the reproductive system.
Broader Impacts The project will enhance the research infrastructure by providing a powerful new tool (C. elegans cell lines) that can be used to probe many areas of biological research. Additionally, local K-12 science teachers will participate in summer internships where they will contribute to the research to create a C. elegans cell line. In addition to broadening their research experience, the teachers will learn how to work with C. elegans, which can be used in elementary and high school laboratory courses to effectively teach genetics. Finally, college students will also be involved in carrying out the research, which will contribute to the training of the next generation of scientists.
Scientific Merit The cells that produce reproductive eggs and sperm are germ stem cells. Understanding how the division of these cells is controlled is important for reproductive health. Germ stem cells divide in a specialized region called an adult stem cell niche. The adult stem cell niche provides signals that cause the germ stem cells to divide to create more germ stem cells rather than enter the process of meiosis, which will produce eggs and sperm. The division of germ stem cells is required to ensure that the germ stem cell population is maintained so that an adequate number of eggs and sperm can be produced. This study focused on the regulation of the division of germ stem cells in the small roundworm, Caenorhabditis elegans. C. elegans is one of the foremost genetic model systems for biomedical research, and it has been used to uncover many aspects of biology that impact human health. Our research identified two new pathways that regulate germ stem cell divisions in C. elegans. One of the new pathways is a hormone that inhibits germ cell divisions. The other pathway arises from the bacteria that the C. elegans eats. This bacterial signal defines a new type of signaling molecule that has the potential to be used as a signal in other animals as well. Our work has also defined experimental conditions that allow the maintenance of C. elegans germ cells as a pure population outside of the animal so that they can be studied independently of other tissues. The use of this experimental system will allow further advances in understanding the regulation of germ stem cell divisions and meiosis. Broader Impacts This project provided the opportunity to train three high school teachers in advanced genetics research. This training enhanced the teacherâ€™s understanding of genetics so that they can impart first-hand knowledge to their students on how genetics research is conducted. The project also provided the foundation for the dissertation of a dual Master's degree/Bachelor's degree student, and training for an undergraduate student and two graduate students.