Zebrafish atlas will help research community to model human disease

An inch-long tropical fish will enjoy improved global exposure thanks to a five-year, $2.7 million grant from the National Center for Research Resources-National Institutes of Health (NIH) awarded to Keith Cheng, M.D., Ph.D., associate professor of pathology, Penn State College of Medicine.

The grant will support the creation of a virtual zebrafish microanatomy atlas for the international research community. The computer-based atlas, which will be integrated into the Web site of the Zebrafish Information Network (ZFIN), will give researchers around the world access to thousands of high-resolution files that will show zebrafish microanatomy at magnifications determined by the user, and will provide three-dimensional images of body structures such as organs.

“There has been phenomenal growth in the zebrafish research community due to the zebrafish’s compelling experimental characteristics and its capacity to model human disease,” said Cheng, who is working with co-investigator Stephen Moorman, Ph.D., of the Robert Wood Johnson Foundation Medical School on the atlas. “This grant grew out of experiments in my laboratory a decade ago. The atlas will make it possible for us to share our detailed zebrafish anatomy, from any point in its lifespan, with researchers around the globe. This data-sharing will speed the pace of discovery for a number of human diseases.”

The atlas will allow scientists to access images of the anatomy of healthy zebrafish to compare to the zebrafish used in their studies of gene functions and disease. The comparisons to the images of healthy zebrafish will allow investigators to quickly detail the anatomical abnormalities associated with a variable manipulated in their experiments.

The zebrafish, a common home-aquarium fish, has proven to be a good model for a variety of human biological processes and diseases. Zebrafish have a rapidly developing, transparent embryo with females producing about 200 eggs per week, giving researchers the quantity of offspring and the short life cycle needed to efficiently study how genetic malfunctions can lead to disease. As vertebrates, zebrafish provide a closer model for humans than yeast or fruit flies, which are also commonly used for medical research. In the early 1990s, Cheng and his team became the first to develop the zebrafish as a medical research model to study the relationship between high rates of mutation and the development of cancer.

“Zebrafish are becoming an ideal research model to determine the functions of individual genes in vertebrates and the timing of gene expression during development in the context of a whole, living organism,” Cheng said. “Strong similarities between fish and mammalian development have led to the discovery of new insights that would have been difficult to obtain using other models.”

The atlas initiative started in 1999 when representatives of the international zebrafish community met at the NIH and assigned to the Cheng lab the task of creating a virtual atlas of normal microanatomy for the growing research community. Cheng has envisioned the field using the atlas infrastructure as the foundation for development of a new approach to understanding biology that will address the problem of information overload.

“We’re calling this new approach Systems Morphogenetics,” Cheng said. “This new, more integrated view of biology will focus on understanding how genes determine form and function during organisms’ life spans, across the spectrum of earthly life forms. Ultimately, I believe this integrated approach will give us a deeper understanding of life and disease.”

Cheng is the organizer of a Federation of American Societies for Experimental Biology symposium on Systems Morphogenetics, which will take place at the Experimental Biology 2005 scientific meeting in April.

The atlas and its progress can be followed at http://www.Zfatlas.psu.edu