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諾貝爾報告 --2008 年諾貝爾生醫獎 -- 發現 HPV 和 HIV PowerPoint Presentation
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諾貝爾報告 --2008 年諾貝爾生醫獎 -- 發現 HPV 和 HIV. 組別 : 第五組. 組員 : 吳佩璇 B9702025 沈孟暵 B9702025 林威佑 B9702032 何宜軒 B9702006 沈玉華 B9702024 林琬錤 B9702036 林栢生 B9702038 吳東霖 B9702012. 目錄. HPV: 科學家簡介 HPV 簡介 How did he find the HPV ?

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諾貝爾報告 --2008 年諾貝爾生醫獎 -- 發現 HPV 和 HIV


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slide1

諾貝爾報告

--2008年諾貝爾生醫獎

--發現HPV和HIV

組別:第五組

組員:吳佩璇B9702025

沈孟暵B9702025

林威佑B9702032

何宜軒B9702006

沈玉華B9702024

林琬錤B9702036

林栢生B9702038

吳東霖B9702012

slide2

目錄

  • HPV:
  • 科學家簡介
  • HPV簡介
  • How did he find the HPV ?
  • HPV病毒E6,E7基因致癌機制
  • HPV疫苗
  • 2. HIV:
  • 研究者簡介
  • HIV簡介
  • 感染機制
  • HIV疫苗及其發展
slide3

報告人:吳佩璇

學號:B9702025

主題:科學家簡介

harald zur hausen
Harald zur Hausen哈拉爾德 楚爾 郝森
  • 德國人
  • 德國海德堡癌症研究中心的榮譽教授、前主任和科學主管
  • 畢生研究乳頭狀瘤病毒
  • 獲得2008年生理醫學諾貝爾獎
slide5

貢獻

  • 發現致瘤人類乳頭狀瘤病毒(HPV)導致子宮頸癌在子宮頸癌切片發現了可致癌的HPV16、18型病毒
  • 發現致瘤人類乳頭狀瘤病毒屬於一個異種病毒家族
slide6

報告人:沈孟暵

學號:B9702025

主題:HPV簡介

slide7
HPV簡介
  • 至少有70多型
  • 感染人類的皮膚及黏膜
slide8
感染方式
  • 直接接觸皮膚及黏膜的小傷口感染
  • 性接觸
  • 新生兒經產道感染
  • 摳弄疣
slide9
HPV結構
  • 種類:DNA病毒
  • 大小:45至50nm間
  • 病毒體不具套膜為二十面體的殼體
  • DNA為雙股環狀
slide10
HPV的基因

(A)The early region:E1-8

1.Transcription

2.transformation

(B)The late region : L1,L2

1.major (L1) and

minor (L2) capsid

proteins

slide11
HPV的基因

Transforming protein,

interacts with growth factor receptors

Initiation of DNA replication

binds to pRB

Transcriptionalregulation/DNA replication

binds to p53

nuclear acid hybridization1
Nuclear Acid Hybridization
  • combining

(1)complementary

(2)single‐stranded nucleic acids

into a single molecule

– a new “hybridized” DNA molecule.

ProbeDNA

Gene ofinterest

Single-strandedDNA from cell

slide19

Southern Blotting

= Nucleic acid hybridization

+

Gel electrophoresis

slide20

Southerrn Blotting

Heavyweight

I II III

Restrictionfragments

Nitrocellulosemembrane (blot)

DNA + restriction enzyme

Gel

Sponge

Papertowels

Alkalinesolution

2

1

3

Preparation of restriction fragments

DNA transfer (blotting)

Gel electrophoresis

Radioactively labeledprobe

Probe base-pairswith fragments

I II III

I II III

Fragment

Film overblot

Fragment

Nitrocellulose blot

4

5

Probe detection

Hybridization with radioactive probe

problems
Problems
  • Originally, he attempted to find HPV DNA in cervix carcinoma(子宮頸癌) by hybridizing tumor DNA with cRNA from planta wart(足部疣) HPV DNA
  • But the result is “negative”
  • He suspected “genetic heterogeneity(異質性)”among HPV DNA type
after problems
After problems
  • He than hybridized samples at *reduced stringency

*Reduced stringency: screen for “related” but not “identical(the same)” HPV types

  • He really found other types of HPV DNA after that
illustrate how was the research done
Illustrate-how was the research done?

Reduced stringency

= with cervical cancer

= healthy

after problems1
After problems
  • He once found a type called HPV11
  • 2 samples from invasive cervix carcinoma showed weak but persistent cross hybridization
  • This typed was then named HPV16
  • Later, HPV18 was also found
  • HPV16 & HPV18 present in 82% of the patients with invasive cervical cancer
illustrate blot hybridizaition with labeled hpv16 dna probe
Illustrate-Blot hybridizaition with labeled HPV16 DNA probe

(positive)

Low stringency

High stringency

1.invasively growing cervical carcinomas -(lanes 2, 4, 5, 7, 9),

2.one dysplasia(發育障礙) (lane 6),

3.two carcinomas in situ of the cervix (lanes1 and 5)

4.one vulval(外陰) carcinoma (lane 3)

(All above were cleaved by BamHl. )

slide27

報告人:何宜軒

學號:B9702006

主題:HPV病毒E6,E7基因致癌機制

slide31

報告人:吳佩璇

學號:B9702025

主題:HPV疫苗

slide32
子宮頸癌疫苗
  • 藍圖

人工培養HPV病毒,減低其毒性或讓其失

去複製的能力,就可當成疫苗注射進人體,

使人體免疫系統記住這個病毒

  • 困境

HPV病毒只能存活於活的皮膚或黏膜組織

上,沒辦法人工培養

slide33
子宮頸癌疫苗
  • 1984年,德國科學家季斯曼已成功複製出HPV的DNA
  • 1988年選出一段L1基因到細菌中表現,合成L1蛋白
  • 此L1蛋白無法用來組裝HPV殼蛋白

slide34
子宮頸癌疫苗
  • 利用聚合酶連鎖反應自行複製子宮頸癌病患檢體DNA並從中找出L1基因,然後嵌入酵母菌DNA中,讓酵母菌合成L1蛋白
  • 利用比較基因學組學合成出來的L1蛋白可以組裝成HPV的殼蛋白
  • 酵母菌合成的L1蛋白就會自行聚合,組成類病毒微粒,為最佳的疫苗材料
slide35

報告人:沈玉華

學號:B9702024

主題:研究者簡介

slide36

研究者

Luc Montagnier

Françoise Barré-Sinoussi

luc montagnier
Luc Montagnier
  • 簡介
    • 法國病毒學家
    • 巴黎巴斯德研究所
  • 研究動機
fran oise barr sinoussi
Françoise Barré-Sinoussi
  • 簡介
    • 法國病毒學家
    • 主要研究寄主本身對AIDS的自主防禦能力
  • 研究動機
slide40
發現病毒過程
  • 早期被誤認為是男同性戀病
  • 開始被關注
    • 累積流行病學數據→有傳染性致因
    • 非同性戀的病例越來越多
  • 調查傳染性病原
    • 發現新的逆轉錄病毒─IDAV
      • 觀察到CD4+ T細胞迅速消失
    • 1986年統一命名「人類免疫缺陷病毒」(Human Immunodeficiency Virus, HIV
slide41
發現一個新病毒

找到了 壞病毒

lav idav htlv
辨識LAV/IDAV和HTLV
  • 實驗:
  • 一對有血友病的兄弟 一個有卡波     西氏肉瘤一個沒有
  • 現象:有愛滋病病症的─IDAV
  •    沒有愛滋病的─HTLV
  • 差別:特別的p24蛋白質

HIV病毒

slide43

報告人:林琬錤

學號:B9702036

主題:HIV簡介

slide45
演變
  • From SIV(Samian Immunodeficiency Virus)
  • Chimpanzees
retroviruses
Retroviruses
  • Oncornavirinae致癌病毒亞科(HTLV)
  • Lentivirinae慢性病毒亞科(HIV)
  • Spumavirinae泡沫病毒亞科
lentivirus
Lentivirus
  • enti-, Latin for "slow“
  • 和神經及免疫抑制性疾病有關
  • deliver a significant amount of genetic information into the DNA of the host cell
hiv human immunodeficiency virus
HIV(Human Immunodeficiency Virus)$
  • 0.1 microns
  • 72 little spikes proteins gp120 and gp41
  • RNAvirus
retrovirus gene
Retrovirus gene
  • 9 genes
    • Gag(group specific antigen)殼體蛋白
    • Pol(polymerase)聚合酶、蛋白酶、整合酶
    • Env(envelope)醣蛋白
retrovirus gene1
Retrovirus gene
  • tat
  • Rev
  • Nef
  • Vif
  • Vpr
  • vpu

control the ability of HIV to infect a cell, produce new copies of virus, or cause disease.

slide51
影片
  • http://www.youtube.com/watch?v=v5LGqi-8eZg
slide53

報告人:林栢生

學號:B9702038

主題:感染機制

t cd4
人類免疫缺陷病毒感染包括輔助T細胞與巨噬細胞等在表面表達CD4分子的細胞人類免疫缺陷病毒感染包括輔助T細胞與巨噬細胞等在表面表達CD4分子的細胞

http://pathmicro.med.sc.edu/flash/hiv2000.html

slide58

報告人:吳東霖

學號:B9702012

主題:HIV疫苗及其發展

development of antiretroviral drugs
Development of antiretroviral drugs
  • 抗reverse transcriptase 藥物
  • 新突變產生
  • 雞尾酒療法
slide60

藥物

Fusion inhibitors

Integrase inhibitors

CCR5 receptor antagonists

development of antiretroviral drugs1
Development of antiretroviral drugs

影響

  • Reduction of the virus load with a concomitant reduction in virus spread
  • A cessation of T cell death
  • Re-emergence of a functional immune system

結果

  • Although antiretroviral drugs are suppressive, they can’t cure infection with HIV
investigating how protection from infection is maintain ed
Investigating how protection from infection is maintained
  • APOBE(蛋白質)會在HIV進行反轉錄成cDNA的階段時,造成其cDNA上鹼基的突變,使得HIV的感染力下降
    • APOBEC (apolipoprotein B mRNA-editing catalytic polypeptide)
  • Vif gene enable HIV-1 to inactive APOBEC.
investigating how protection from infection is maintained
Investigating how protection from infection is maintained
  • TRIM5-α(monkey)gene blocks virus capsid uncoating
    • TRIM5-α: the tripartite motif–containing 5-α gene
  • 人類體內也有類似蛋白質但效果不彰
investigating how protection from infection is maintained1
Investigating how protection from infection is maintained
  • Cellular miRNA can also interfere with HIV replication
  • However, HIV-1 can modify miRNA expression profiles in the infected cell
investigating how protection from infection is maintained2
Investigating how protection from infection is maintained
  • Medical attempts to induce protection include male circumcision(割包皮), and randomized, controlled clinical trials have demonstrated the efficacy of this in reducing female-to-male transmission of HIV-1 by 50%–60%