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Model Systems in Cancer Research: Fish

Course describing model organisms and examples of their use in cancer research

Zebrafish cancer model

Video of a live zebrafish with melanoma (Zon lab).

Zebrafish that express a mutated form of the human BRAF oncogene develop black-pigmented moles. When they were also made to be deficient for the p53 gene, the moles developed into invasive melanomas resembling human cancers.

Transparent zebrafish

Video of the Casper fish heart beating (Zon lab)

"Casper" is a new zebrafish model that will facilitate metastasis studies. It remains transparent as an adult allowing direct visualization of metastatic cancer cells as they spread.

Metastasis

A narrated 3D animation about the process of metastasis.

Activities in the fish lab

The class will go with Shibani to the Moens lab after the lecture from ~3-3.30pm. Based on topics discussed in the lecture, we will do the following: 

1. Distinguish between zebrafish embryos/larvae at different developmental stages, and discuss the impact of temperature on the rate of development.

2. Observe the heartbeat in the embryo and discuss the practical aspects of gridlock mutant and chemical genetics screen covered in the lecture.

3. Identify various characteristics of the embryos under the microscope, such as the developing eye, ear, heart, circulating blood cells, cerebellum, yolk sac, pigmentation patterns, notochord and twitching motion in the late stages.

Overall we will develop an appreciation of why the large, transparent embryos that develop external to the female are excellent models for both developmental and cancer biologists.

Lecture Slides and Papers

Zebrafish (Danio rerio)

Lecture videos are available for viewing in the left column. They will be used to illustrate points about the following:

  • Zebrafish cancer models
  • New 'Casper' zebrafish model is facilitating metastasis studies
  • The steps involved in tumor metastasis

 Required/Encouraged Reading

1. A great review covering history, pros/cons, techniques, general zebrafish disease models.

"Animal models of human disease: zebrafish swim into view" by Graham Lieschke and Peter Currie.

2. This review specifically and comprehensively deals with zebrafish models of cancer.

"Zebrafish as a Cancer model" by Harma Feitsma and Edwin Cuppen.

Additional Reading

1. Review covering the history of zebrafish research.

Headwaters of the zebrafish -- emergence of a new model vertebrate." by David Grunwald and Judith Eisen.

2. Review about cancer biology in zebrafish covers chemical screens and TILLING.

"Cancer genetics and drug discovery in the zebrafish" by Howard Stern and Leonard Zon".

3. Generating the transparent "Casper" fish. See Figure 4 for melanoma metastasis study.

"Transparent Adult Zebrafish as a Tool for In Vivo Transplantation Analysis" by White RM et al.

4. Metastasis study using a novel zebrafish xenograft model.

"High-resolution imaging of the dynamic tumor cell–vascular interface in transparent zebrafish" by Stoletov K et al.

Books in Library

These books are on course reserve in the first floor copy room of the Arnold Library, Weintraub building for two weeks after class. If you are interested in a more in depth view of the lecture topics take a look.

1. "Of fish, fly, worm, and man : lessons from developmental biology for human gene function and disease" by Nüsslein-Volhard, C. , Krätzschmar, J. Genetic research in worm, fly, fish, and rodent models reveals signaling pathways of biomedical significance . The book relevant to lectures 2-6 in this course.

2. “Zebrafish” by Christiane Nusslein-Volhard  and Ralf Dahm. A laboratory manual providing in depth information on most techniques used for zebrafish research.

3. "The Zebrafish: Biology" (eds) H. William Detrich,III, Monte Westerfield, Leonard Zon . A zebrafish sourcebook, with even more in-depth discussion of molecular biology and genetics of the zebrafish. Useful overview in 'Introduction' chapter.

On campus resources - FHCRC fish labs

FHCRC scientists working with fish model systems:

1. Cecilia Moens: Vertebrate brain regionalization during early development.

2. Mark Roth: Suspended animation and "metabolic hibernation".

3. Katie Peichel Mechanisms underlying evolutionary processes in the threespine stickleback fish.

Online resources

These are excellent resources for zebrafish information. 

1. An online database for collects, curates, and disseminates information about zebrafish biology.

http://zfin.org/

2.  A comprehensive free online guide for laboratory use of zebrafish (Danio rerio).

The Zebrafish Book

3. A resource center that acquire resources from the research community, maintains them, and redistributes them upon request for a nominal price

Zebrafish International Resource Center

4. Educational resource for zebrafish courses. See the fun "Virtual Experiments" section for movies of the beating hearts in casanova mutants and the developmental staging experiment.

Zebrafish in the Classroom