Sea Urchins as Models for Aging and Cancer Research

Team Members:

Dr. Riss Kell, Postdoctoral Scientist

Jennifer Polinski, Senior Research Scientist

Reanna McAtee, Laboratory Technician

Overview

The oceans are home to many of the earth’s longest-lived animals with several marine vertebrates and invertebrates documented to live for centuries without showing signs of aging. At GMGI our goal is to understand mechanisms of exceptional longevity in these animals and apply this knowledge to promote healthy aging and prevention of age-related degenerative disease and cancer in humans. To achieve this goal, we are using sea urchins as research models to study the molecular and cellular mechanisms that underlie long-term maintenance of tissue function and resistance to disease. 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.

Understanding Mechanisms of Longevity and Healthy Aging

Sea urchins represent excellent models for understanding molecular, cellular, and systemic mechanisms underlying longevity and healthy aging. There are about 1,000 extant sea urchin species that exhibit a wide range of lifespans, including species with exceptional longevity. The red sea urchin (Mesocentrotus franciscanus) is one of the earth’s longest living animals, reported to live more than 100 years with indeterminate growth and negligible aging. In contrast, other sea urchin species are reported to live for only a few years, providing a unique opportunity for comparative studies.

We are conducting comparative genomics between long- and short-lived sea urchin species to discover genes and pathways that regulate longevity and disease resistance. These studies have uncovered expanded gene families in long-lived species that play a role in innate immunity, sensory nervous system, and genome stability. We have also identified unique molecular signatures involved in genomic regulation, mRNA fidelity, protein homeostasis, and mitochondrial function that promote long-term maintenance of tissue homeostasis, disease resistance, and negligible aging.

We are using comparative transcriptomics to determine how gene expression changes with age in different tissues of sea urchins in order to understand how these animals maintain tissue function without accumulation of cellular damage over time. We have a particular focus on the role of the nervous system and the immune system, which provide widespread systemic benefits maintaining homeostasis in other tissues throughout the body.

Investigating Naturally Occurring Resistance to Cancer

Sea urchins are noted for the absence of cancer despite the fact that some species are very long-lived (living in excess of 100 years), possess high regenerative capacity, and lack an adaptive immune system. Using sea urchins as a cancer resistant animal model our goal is to investigate mechanisms of naturally occurring cancer prevention that could lead to effective new therapies for neoplastic disease.

We are investigating the role of the innate immune system in protecting sea urchins from cancer. Our goal is to identify novel interactions between the DNA damage response (DDR) and the innate immune system that enhance the immune system’s ability to recognize and remove damaged cells as a cancer prevention mechanism. The results of this work will provide new insights into antitumor immunity that may ultimately lead to novel therapeutic strategies to enhance the innate immune system’s ability to combat cancer.

The genomes of long-lived sea urchins have expanded repertoires of genes involved in genome maintenance including multiple copies of key DNA repair and tumor suppressor genes. We are investigating the role of these tumor suppressor genes in protecting sea urchins from cancer and developing a strategy to identify novel tumor suppressor mechanisms that could ultimately lead to new approaches for prevention or treatment of cancer.

Developing New Cell Culture Tools to Promote Functional Genomic Studies

For more than a century, sea urchins have served as important research models that have advanced our understanding of key biological processes including cell cycle regulation, the respiratory burst, the role of chromosomes in inheritance, and gene regulatory networks of early development. However, their full potential as research models has yet to be realized due to the limited tools available to test gene function. As part of a large collaborative effort within the echinoderm research community, our goal is to create the next generation of molecular and cell culture tools to enable new research questions across a broad range of disciplines (e.g. developmental biology, tissue regeneration, biomineralization, response to environmental stress, negligible aging, cancer resistance, neurobiology, innate immunity). This work will transform the ability to use sea urchins and other echinoderms as research models that promises to add a new era of discovery to their remarkable history and to transition these organisms into a mainstream model of discovery and translation.

Publications

Click here to see publications

Polinski, J.M, Castellano, K.R., Buckley, K.M, and Bodnar, A.G. (2024) Genomic signatures of exceptional longevity and negligible aging in the long-lived red sea urchin. Cell Reports 43(4) 114021. DOI: https://doi.org/10.1016/j.celrep.2024.114021

Polinski, J.M., Zimin, A.V., Clark, K.F., Kohn, A.B., Sadowski, N., Timp, W., Ptitsyn, A., Khanna, P., Romanova, D.Y., Williams, P., Greenwood, S.J., Moroz, L.L., Walt, D.R. and Bodnar, A.G. (2021) The American lobster genome reveals insights on longevity, neural, and immune adaptations. Science Advances Vol. 7, no. 26, eabe8290 DOI: 10.1126/sciadv.abe8290 https://advances.sciencemag.org/content/7/26/eabe8290

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

Emerson, C.E., Reinardy, H.C., Bates, N.R. and Bodnar, A.G. (2017) Ocean acidification impacts spine integrity but not regenerative capacity of spines and tube feet in adult sea urchins. Royal Society Open Science 4: 170140. http://dx.doi.org/10.1098/rsos.170140

Bodnar, A.G. and Coffman, J.A. (2016) Maintenance of somatic regenerative capacity with age in short- and long-lived species of sea urchins. Aging Cell 15, 778–787 doi: 10.1111/acel.12487. https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12487

Reinardy, H.C., Chapman, J. and Bodnar, A.G. (2016) Induction of innate immune gene expression following methyl methanesulfonate-induced DNA damage in sea urchins. Biology Letters 12: 20151057. https://royalsocietypublishing.org/doi/full/10.1098/rsbl.2015.1057

Bodnar, A.G. (2016) Lessons from the sea: Marine animals provide models for biomedical research. Environment: Science and Policy for Sustainable Development, 58:2, 16-25. https://www.tandfonline.com/doi/abs/10.1080/00139157.2016.1134020?journalCode=venv20

Reinardy, H.C. and Bodnar, A.G. (2015)  Profiling DNA damage and repair capacity in sea urchin larvae and coelomocytes. Mutagenesis 30, 829-839. doi:10.1093/mutage/gev052. https://academic.oup.com/mutage/article/30/6/829/2622772

Reinardy, H.C., Emerson, C.E, Manley, J.M. and Bodnar, A.G. (2015) Tissue regeneration and biomineralization in sea urchins: role of Notch signaling and presence of stem cell markers. PLoS ONE 10(8): e0133860. doi:10.1371/journal.pone.0133860. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534296/

Bodnar, A.G. (2015) Cellular and molecular mechanisms of negligible senescence: insight from the sea urchin. Invertebrate Reproduction & Development, 59:sup1, 23-27. https://www.tandfonline.com/doi/full/10.1080/07924259.2014.938195

El-Bibany, A.H., Bodnar, A.G. and Reinardy, H.C. (2014) Comparative DNA damage and repair in echinoderm coelomocytes exposed to genotoxicants. PLoS ONE 9(9): e107815. doi:10.1371/journal.pone.0107815

Du, C., Anderson, A., Lortie, M., Parsons, R. and Bodnar, A. (2013) Oxidative damage and cellular defense mechanisms in sea urchin models of aging. Free Radical Biology and Medicine 63, 254-263.

Bodnar, A. (2013)  Proteomic profiles reveal age-related changes in coelomic fluid of sea urchin species with different life spans. Experimental Gerontology 48, 525-530.

Talbert, E., Bodnar, A., Morré, D.M. and Morré, D.J. (2013)  Age-related NADH oxidase (arNOX) activity is significantly reduced in coelomic fluid of long-lived sea urchins. International Aquatic Research 5:2.

Loram, J. and Bodnar, A. (2012) Age-related changes in gene expression in tissues of the sea urchin Strongylocentrotus purpuratus. Mechanisms of Ageing and Development 133, 338-347.

Loram, J., Raudonis, R., Chapman, J., Lortie, M. and Bodnar, A. (2012)  Sea urchin coelomocytes are resistant to a variety of DNA damaging agents. Aquatic Toxicology 124-125, 133-138.

McCaughey, C. and Bodnar, A. (2012) Investigating the sea urchin immune system: Implications for disease resistance and aging. Journal of Young Investigators 23(6), 25-33.

Bodnar, A.G. (2009) Marine invertebrates as models for aging research. Experimental Gerontology 44, 477-484.

Ebert, T.A., Russell, M.P., Gamba, G. and Bodnar, A. (2008)  Growth, survival, and longevity estimates for the rock-boring sea urchin Echinometra lucunter lucunter (Echinodermata, Echinoidea) in Bermuda. Bulletin of Marine Science 82, 381-403.

Francis, N., Gregg, T., Owen, R., Ebert, T. and Bodnar, A. (2006)  Lack of age-associated telomere shortening in long- and short-lived species of sea urchins. FEBS Letters 580, 4713-4717.