Sea Urchins as Models for Aging and Cancer Research
The oceans are home to many of the earth’s longest-lived animals with several marine vertebrates and invertebrates documented to live for centuries. A better understanding of the mechanisms by which these animals achieve their extraordinary life histories may reveal effective defenses against the destructive process of aging and suggest novel avenues to prevent or treat human age-related degenerative diseases. At GMGI, we are using sea urchins as models to unlock the genetic secrets of living a long and healthy life. Some species of sea urchins can live to extraordinary old ages (more than 100 years) with life-long growth and reproduction, no evidence of age-related decline, and no reported cases of cancer. Because sea urchins share a close genetic relationship with humans, they are ideal models to investigate the molecular and cellular pathways contributing to longevity and disease resistance with direct relevance to human health.
Our goal is to use a genomic approach to identify the key genes and cellular pathways involved in long-term maintenance of tissues and resistance to cancer, and to develop new genetic tools to test the functional roles of these pathways. Our approach is to compare the genomes of sea urchin species with different lifespans and evaluate age-related gene expression with a focus on the nervous system, immune system, and stem cells. Further, we are investigating the response of sea urchin cells to DNA damaging agents to identify cellular pathways that protect their cells from damage.
While sea urchins have been invaluable for numerous biological findings, the next generation of discoveries may be hindered by a lack of tools available for scientists to study these animals through all stages of development, from embryo to adult. At GMGI, we are working in collaboration with scientists at Brown University and the University of Alabama, Birmingham to develop tools to advance functional genomic studies in sea urchins using the variegated sea urchin (Lytechinus variegatus) as a model. With support from a grant from the National Science Foundation, the tools developed in this project involve establishing and distributing protocols for genetic modification of embryos, animal husbandry, and cell culture. At GMGI, we are focused on all aspects of cell culture including developing a molecular test to differentiate males and females, cryopreserving sperm, eggs, and embryos, and establishing cell culture methods and stem cell lines for sea urchins. Once these new tools and techniques are distributed to the scientific community, an entirely new suite of discoveries will be possible concerning how eggs and sperm interact at fertilization, embryo development, nerve cell generation, sex determination, molecular response to environmental stressors, and tissue regeneration.
Polinski, J.M., N. Kron, D.R. Smith, and A.G. Bodnar. (2020) Unique age-related transcriptional signature in the nervous system of the long-lived red sea urchin Mesocentrotus franciscanus. Scientific Reports. 10: 9182. doi:10.1038/s41598-020-66052-3 https://www.nature.com/articles/s41598-020-66052-3