Gene Expression

1. Gene Expression Group Awesome (aka Team Water Spill) Geoduck Land Summer Institute, 2012 Group Members Amy Oakley Katie Clark Sharsti Sandall Jim Burnette Sarah Stockwell Krissi Hewitt Lori Kayes Steve Chordas

2. Background Information Students will already… • Have had a brief introduction into gene expression • Know how transcription and translation work • Know that there are technologies to measure gene expression, both genome-wide and for specific genes • Have been introduced to experimental design

3. Understand that gene expression regulates cell function Understand the flow of genetic information from DNA to phenotype Appreciate the relevance of gene expression to science and society Effectively work in groups to model the collaborative process of science Think critically about how experimental evidence answers a scientific question Unit Learning Goals Students will:

4. Describe how a change in gene expression can lead to changes in phenotype Analyze and interpret graphs and scientific images Synthesize data into a hypothesis to connect gene expression and phenotype Apply a similar hypothesis to a real situation Develop, articulate, and defend a position on the ethics of genetic testing Learning Outcomes for Teachable Tidbits Students will be able to:

5. Teachable Tidbit 1 You are a scientist wandering the Galapagos Islands, and you notice that finches have different beak sizes. You think this might be based on differences in gene expression. Upon returning to your island laboratory, you find that a gene called bone morphogenic protein 4 (Bmp4) varies across finch species.

6. A C Hypothesis to explain relationship between Beak Size (cm) Gene Expression Levels of Bmp4 Type of Finch Species Type of Finch Species B Abzhanov, A. et al. Science 2004 2 min!

7. Design an Experiment • Based on the class hypothesis, design an experiment with at least 1 control. • Predict the outcome. • Would this outcome support your hypothesis? 5 min!

8. Bmp4 The Bmp4 signal changes gene expression which changes phenotype

9. The Bmp4 signal changes gene expression which changes phenotype Bmp4

10. The Bmp4 signal changes gene expression which changes phenotype Bmp4 Transcription factors turn genes on or off

11. The Bmp4 signal changes gene expression which changes phenotype Bmp4 Transcription factors turn genes on or off The cell changes!

12. The Bmp4 signal changes gene expression which changes phenotype Bmp4 Cell changes can include: • Cell growth and division • Cell death • Pausing the cell cycle • Cell movement Transcription factors turn genes on or off The cell changes!

13. Teachable Tidbit 2 New York Times Article--for Tomorrow

14. Main Points of Article (for SI) • 2 classes of ocular melanoma: after treatment • Class 1 --> 100% survival • Class 2 --> 20% survival • Previously, the only way to determine prognosis was by tumor size…but this wasn’t very accurate • Researchers then compared gene expression between tumors • 12 signature genes can differentiate tumor class, thus predicting survival • Knowing tumor class does not change treatment or outcome • Doctors are split as to whether to offer this test

15. Clicker Questions 1. What is ocular melanoma?A) skin cancer of the earB) hyperpigmentation of the skinC) skin cancer of the eye D) sleeping disorder

16. Clicker Questions 2. Describe the new test that distinguishes between Class 1 and 2 ocular melanomaA) measure tumor sizeB) gene expression testC) DNA sequence testD) no test needed; there is no difference

17. How does the article relate to finches??? Small group discussion 5 min!

18. Onken et al J Mol Diagn. 2010 Onken M D et al. Cancer Res 2004

19. Teachable Tidbit 2Think-Pair-Share Onken et al J Mol Diagn. 2010

20. Ethical Implications for Genetic Testing • Doctors in New York Times article conflicted • Imagine you are a doctor. Individually reflect on whether you would offer this test to your patients. • First list the pros and cons… • Choose a position and be prepared to defend it. 5 min!

21. Discussion Students who would offer the test stand by the chalkboard Students who would NOT offer the test stand by the corkboard Write your reasons for your position on the board/paper Write your reasons for your position on the board/paper Come back as a group and discuss each position and reasons • 1 minute reflective paper • Indicate your original position on the top of the paper • Defend the opposite side

22. Summative Assessment (SI) Assuming that there are multiple classes of ovarian tumors, and some are treatable and some are not, what information would you need to know to design a test to determine whether a tumor is treatable or not? List and describe at least 3 (of the 5) critical components: Answer: 1. Gene expression levels of different classes of tumor 2. What genes are changing, which aren’t? 3. Tumor vs normal tissue samples 4. Long-term survivorship of patients 5. Genome-wide expression

23. Summative Assessment (SI) Assuming you find a good candidate gene to determine tumor class, draw a graph showing the difference in gene expression between the 2 tumor classes and a graph of survivorship by tumor class. If you had ovarian cancer, would you want your tumor tested? Why or why not?