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Model Systems in Cancer Research: Fly

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

Cell division in fly embryo

Wound healing in fly embryo

wound healing

Click on image to view video.

Visualizing actin with GFP in fly embryo. Embryo was laser ablated and wound repair response followed by time lapse microscopy. Upon ablation, the wound expands then initiates closure. Actin does not accumulate at the wound edge, rather the actin cap associated with each nucleus is disrupted. (Parkhurst lab, FHCRC).

Online resources

1. A virtual library containing comprehensive list of links to fly information and resources.

http://www.ceolas.org/fly/ 

2.  A key internet resource for fly researchers.

http://flybase.org/

3. A fun online exhibit of mutant flies.

http://www.exploratorium.edu/exhibits/mutant_flies/mutant_flies.html

4. Great images, movies and interactive features to explain fly development.

 http://flymove.uni-muenster.de/

5. Encyclopedia of fly genes and development.

http://www.sdbonline.org/fly/aimain/1aahome.htm 

6. Where do the fly folks get the weird names for their genes? Not comprehensive but a fun website explaining the origins of fly nomenclature.

http://www.flynome.com/cgi-bin/search?source=recent 

 

Activities in the fly lab

The class will go with Laura to the Edgar lab after the lecture from ~3-3.30pm. Based on topics discussed in the lecture, we will get to see/do the following:

1. Separate male and female flies to set up a cross - a skill that is essential for any genetic experiment.

2. Screen for flies with gene mutations that cause tissue overgrowth - how awesome! You will get a hands-on feel for a screen involving tissue overgrowth in the fly eye.

3. Look at how the Gal4/UAS system works to turn on genes like GFP. We can observe cool segmentation patterns in the tissue of living fly larvae.

Overall, we will get a sense of the entire fly lab set up.

Lecture Slides and Papers

Fly (Drosophila melanogaster)

Lecture videos

 are available for viewing in the left column. View them before class to understand points about the following:

  • Cell division in fly embryo
  • Wound healing in the fly

Required/Encouraged Reading

1. A excellent short review about the advantages of the fly model and some cancer lessons it has taught us.

"What’s All the Buzz? Fruit Flies Provide Unique Model for Cancer Research" by David Tenenbaum

 2. Another great review on the importance of multicellular models like the fly in studying malignant changes in tissue size, migration and tumor microenvironment. Also, covers how discoveries in flies can guide human therapeutics.

"Drosophila models for cancer research" by Marcos Vidal and Ross L Cagan

3. An important article demonstrating how studies on a pathway controlling organ size in the fly lead to the identification of a homologous pathway in mammal, which when dysregulated caused tumorigenesis.

Additional Reading
1. An article showing how the fly model has provided insight into how cell polarity disruption contributes to tumor progression.
2. An article where the fly model is used to demonstrate that the oncogenic background of tissues makes a distinct contribution toward metastatic development.
3. An article on a robust cell-type-specific Drosophila cancer model in which malignant cells are created by mutations in genetic pathways thought to be driving forces in a homologous human cancer.

Books in Library

The following books are on course reserve in copy room of the the Arnold Library in the Weintraub building for two weeks.If you are interested in a more in depth view of Drosophila genetics and techniques take a look at books 2-4.

1. "Of fish, fly, worm, and man : lessons from developmental biology for human gene function and disease" by C. Nüsslein-Volhard, and J. Krätzschmar. 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. "Fly pushing : the theory and practice of Drosophila genetics" by Ralph Greenspan.


3. "Lords of the fly : Drosophila genetics and the experimental life"by Robert Kohler.


4. "The making of a fly : the genetics of animal design" by Peter Lawrence.

On campus resources - FHCRC fly labs

FHCRC scientists working with the fly model system:

1. Bruce Edgar: Cell cycle and cell growth in fly wing, eye, and intestinal stem cells

2. Robert Eisenman: Regulation of cell proliferation, growth and differentiation by transcription factors (Myc-Mad-Max)

3. Steven Henikoff: Epigenetic inheritance and chromatin structure

4. Harmit Malik: Evolutionary studies of genetic conflict

5. Susan Parkhurst: Fly development, wound healing, cytoskeletal dynamics, transcription repression

6. Suzanne Rutherford: Evolution, genetic variation