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你认为如下电影，哪一部最烂？

Which is the worst movie? Take this quiz and choose between Night Banquet, The Promise, House of Flying Daggers, and Hero to find out!

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你认为如下电影，哪一部最烂？

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  1. 你认为如下电影，哪一部最烂？ 夜宴 无极 十面埋伏 英雄

  2. 小测验 signal response Gene A Signal signal response Gene A Signal Gene A has a loss-of-function mutation If Gene A is a positive factor, the mutation should enhance the signal response A: Yes. B: No Gene A has a gain-of-function (hyperactive) mutation If Gene A is a negative factor, the mutation should enhance the signal response A: Yes. B: No

  3. Gb (-): No mating response mating response Gb mating response A: Ga Gb C: not sure B: mating response Gb Ga More test The G protein complex plays a critical role in yeast mating response Ga (-): hyper response, always want to mate mating response Ga Ga(-) & Gb(-):No mating response

  4. Inductive signaling Lateral signaling A A B B Different Signaling strategies Asymmetric division A B Born to be different Between the brothers American way

  5. Asymmetric division A B Born to be different

  6. From Alberts et al. Molecular Biology of Cell

  7. Vegetal pole tissue induces animal pole tissue to produce mesodermal tissue. From Alberts et al. Molecular Biology of Cell

  8. Discovery of the Spemman organizer

  9. Spemann and Mangold

  10. Inductive signaling A B

  11. RTK/RAS/MPK pathway growth factor P RTK GRB2 Ras GAP GDP SOS Ras GTP -P Raf SUR-8 phosphatases +P + P Kinases -P MEK 14-3-3 KSR CNK HSP etc. -P +P MAPK +P Transcription factors A: This pathway is the same between human and the worms or flies. B: Some but not all genes are the conserved in these organisms. C: This pathway is very different between human and the worms or the flies.

  12. GF RTK GRB2 SOS RAS RAF MEK MPK TF About this pathway • Driven by cancer research and developmental genetics • One of the first signaling pathways extensively characterized by biochemists and geneticists • One of the first systems that demonstrated the extensive collaboration between biochemists and geneticists. Broke the boundaries between disciplines. • The discovery of the conservation of this pathway powerfully pushed the use of model organisms

  13. A Drosophila compound eye With ~800 ommatidium

  14. WT sevenless

  15. Brenner & Benzer’s exploratory vision in 1960s Sydney Brenner Seymour Benzer MRC Caltech C. elegans Drosophila

  16. The Sevenless story 1960s. Benzer decided to study behavior using Drosophila 1970s Benzer paid most attention to development of eye. 1970 Don Ready isolated the first sevenless mutation 1970s. Ready: all ommatidia have the same structure, but they do not have the same lineage origin 1976. Ready: retina = neurocrystalline. Previously formed ommatidia as templates for further patterning. 1980s. Tomlinson: sequential cycles of local cell-cell interactions 1987: Sevenless was cloned. First RTK in Development. By Hafen and Rubin. Cell; Banejee and Benzer. Cell. Landmark.

  17. How do they know it is a receptor or a signal? Sev Undifferentiated cell R7 photoreceptor cell 1. Mosaic analysis

  18. About mosaic analysis A genetic mosaic is an organism carrying cells of different genotypes Question: A somatic mutation in our body leads to a mosaic genotype regarding the gene containing the mutation. A: agree. B. disagree. C. not sure.

  19. About mosaic analysis Most of the classical geneticists have been doing germ-line mutagenesis. Therefore, all cells in a given animal have the same genotype (non-mosaic). A: agree. B. disagree. C. not sure.

  20. * * * * * * * * * * Somatic Recombination

  21. With recombination A B A B A B a b a b a b Mitotic recombination: generating mosaic in Drosophila No recombination A B a b A B a b A B a b 1. Rare. Occur in G2 2. Enhanced by x-ray radiation.

  22. Sevenless mosaic analysis From Hartwell et al. textbook A: Sev is a signal B: Sev is a receptor C: not sure

  23. Sev receptor ? Undifferentiated cell R7 photoreceptor cell Why Sev is a receptor? • Mosaic analysis determined that they act in R7 • Structurally similar to receptor tyrosine kinase • The protein is expressed in the R7 membrane

  24. Discovery of the Bride of Sevenless • 1988, BOSS was isolated by Larry Zipurski by the similar method - failure to response to UV. • It has exactly the same Sevenless phenotype Why was it called BOSS?

  25. Mosaic analysis of Boss X-ray W- boss- white boss- W- boss- W- boss- W- boss- W+ boss+ W+ boss+ red Boss+ W+ boss+ W+ boss+ Mitotic cross over Boss acts in A: R7 B: R1 C: R6 D: R8 E: not sure

  26. RT fate is induced by RTK activation Sev receptor Boss signal R8 Undifferentiated cell R7 photoreceptor cell Boss Sev R7 differentiation

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