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2004 Nobel Prize in Medicine or Physiology

2004 Nobel Prize in Medicine or Physiology. The discovery of odorant receptors and the organization of the olfactory system. 2004 Nobel Prizes Winner in Physiology or Medicine. Linda B. Buck. Richard Alex. Three assumptions. Odorant Receptor. Signal. Location. GPCR 的研究.

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2004 Nobel Prize in Medicine or Physiology

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  1. 2004 Nobel Prize in Medicine or Physiology The discovery of odorant receptors and the organization of the olfactory system

  2. 2004 Nobel Prizes Winner in Physiology or Medicine Linda B. Buck Richard Alex

  3. Three assumptions Odorant Receptor Signal Location

  4. GPCR的研究 • GTP dependent increases in adenylyl cyclase activity in the cilia of olfactory sensory neurons • cAMP could alter membrane potential

  5. 實驗方法 找出所有GPCR基因所有的共同基因片段 插入引子 PCR出大量樣品 樣品進行電泳 使用限制酶切割 進行電泳分析

  6. 利用特殊引子PCR

  7. 電泳分析 純化

  8. 電泳分析 限制酶切割 Sample 1 Sample 2

  9. 比對

  10. Linda B. Buck在2003年發表的論文The human olfactory receptor gene family 339種嗅覺受器的基因（intact OR genes） 297種的偽嗅覺基因（OR pseudogenes） 分布在人類21條染色體的51個位置 172種的次家族（Subfamilies）

  11. 嗅覺受器基因在染色體中的分佈

  12. 受器

  13. Generic Structure of an Odorant Receptor

  14. G Protein 作用機制 化學物質 GPCR Adennylyl Cyclase GPCR cAMP

  15. 僧帽細胞 嗅球 嗅小球 篩骨 嗅覺受器

  16. Olfactory pathway • Odorant molecules • Olfactory receptor cell • Axon • Filaments of olfactory nerve • Olfactory bulb • Brain

  17. Olfactory bulb

  18. 嗅覺產生

  19. 嗅覺系統 • “Just like letters of the alphabet are used in different combinations to form different words,…..”Linda B. Buck • 解構→傳送→合成→??(未來發展) • 個體內信息的差異大 ↓ 個體間信息的差異小 • 受器辨識化學結構上的特性 • 大略示意圖

  20. OC ODORANTS OR&OB O F O L A C T R Y

  21. 氣味分子的混合

  22. 嗅覺和味覺的比較

  23. Sensory system • Visual perception ── light • Somatosensory ─ pressure,temperature • Hearing ── pressure • Taste ── molecules • Olfaction ── molecules

  24. Olfactory receptor Olfactory cilia Supporting cells Basal cells (stem cells) Taste bud Gustatory cells Supporting cells Basal cells (stem cells) Receptors

  25. Olfactory pathway • Molecules • Olfactory receptor (dendrites) • G-protein → c-AMP → Na+ Ca+ channels → Action potential • Axon • Olfactory bulb

  26. Gustatory pathway • Chemical molecules - dissolved in saliva • Gustatory cells • Neurotransmitter • Action potential • Taste fibers • brain

  27. G-protein, transduction • Sweet： G protein-coupled receptors • Bitter ： G protein-coupled receptors • Salt ： Na+ transduction (depolarization) • Sour ： H+ permeate channels Inhibit the K+ channel

  28. Taste transduction depolarizes the receptor cells: →neurotransmitter releasing • Neurotransmitter • → cells (cell to cell communication) • → synapse → nerves → brain

  29. Olfactory Receptor → dendrites Odorant molecules over 1000 kinds Gustatory Receptor → cells neurotransmitter Four tastes Bitterness Saltiness Sweetness Sourness Comparison

  30. Summary • GPCR • 路徑(◎未經視丘) • 基因無內插子 • 嗅覺產生

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