From Ilya Mechnikov discovering phagocytosis in starfish larvae to Hodgkin and Huxley defining the principles of nerve conduction in the giant axons of squid, aquatic animal models have influenced our understanding of human biology for over 100 years.
Yet the power of these marine models extends past the realm of basic biology and into the sphere of translational medicine, offering unique versatility for pathogenic exploration that cannot be found in other animal models.
This facet was on marked display at the “Aquatic Animal Models for Human Disease and Midwest Zebrafish” conference held at the University of Wisconsin-Milwaukee School of Freshwater Sciences in July.
Simplicity and a diversity of tools are the prominent advantages of aquatic models of human disease, according to developmental biologist Anthony De Tomaso, Ph.D., associate professor at the University of California, Santa Barbara.
Such is the case with his study of Botryllus schlosseri, a star-shaped invertebrate whose extracorporeal vasculature—coursing along the surface of its body—allows for direct examination of the interactions between immune cells.
“Basically it is a simplified model for understanding self/nonself recognition or allorecognition,” said Dr. De Tomaso. “Our [human] immune cells are running around inside of our bodies, while in Botryllus, the cells are outside the body. Thus you can touch them or watch them come into contact with each other, all within two sessile cell layers.”
Allorecognition enables genetically compatible Botryllus tunicates to form colonies, but also features in fusion-rejection pathways that functionally mimic how the human body accepts or rejects organ transplants.
In humans, allorecognition is governed by the major histocompatibility complexes, which are the most diverse gene family in vertebrates. In contrast, histocompatibility in Botryllus is governed by single locus—fuhc—that encodes two highly polymorphic genes. Dr. De Tomaso has uncovered that these two inputs let Botryllus’ cells “integrate multiple signaling events from the cell surface and make a decision on a response.”
These pathways have been highly conserved throughout metazoan evolution, suggesting that understanding chordate histocompatibility can provide clinically relevant information on immune processes such as tolerance and education, especially for natural killer cells, according to Dr. De Tomaso.
Another translational feature of Botryllus involves a fierce competition between the stem cells of two tunicates fusing into a new clonal chimera. In some incidents, circulating stem cells from one animal will try to hijack the germline or somatic cells of its new partner.
This cellular parasitism hearkens to the aggressive nature of malignant tumors and cancer stem cells.
“The Botryllus system has a natural situation where variation in stem cell properties—growth, migration, competition—provides a definite correlation to why one stem cell population is better than the next,” said Dr. De Tomaso. “This is the other biomedical aspect of our work. Botryllus could provide clues as to why some cancer stem cells are better at migrating or self-renewing.”