浙江大学医学院：《医学分子生物学 Molecular Cell Biology Gene》课程教学资源（PPT课件讲稿）导论（主讲：许正平）

Molecular Biology in Medicine 医学分子生物学 许正平 zpxu@zju.edu.cn

Molecular Biology in Medicine 医学分子生物学 许正平 zpxu@zju.edu.cn

BRAIN EYES HEART Nerve signals warn the rest The pupils Adrenalin and noradrenalin of the body. The brain als expand The increase the heart rate releases hormones that person gets activate the adrenal gland tunnel vision LUNGS The bronchi relax and ADRENAL MEDULLA more air can flow into the produces and lungs. Respiration rate secretes adrenalin and noradrenalin ADRENAL CORTEX produces and secretes MUSCLE TISSUE cortisol The blood flow to the muscles increases adrenal and they contract medulla cortisol renal LIVER noradrenalin produces sugar that is released adrenal into the They STOMACH AND INTESTINES FAT CELLS The blood flow to the digestive release fatty system is decreased acids into the http://www.nobelprize.org/nobelprizes/chemistry/laureates/2012/ bloodstream popular-chemistryprize2012. pdf

http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2012/ popular-chemistryprize2012.pdf

导论

一、导论

医学分子生物学 定义: 从分子水平研究人体在正常和疾病状态下生命活动 及其规律的一门科学 重点: 人体生物大分子和大分子体系的结构、功能、相互 作用及其同疾病发生、发展的关系 分子医学 Molecular medicine

定义： 从分子水平研究人体在正常和疾病状态下生命活动 及其规律的一门科学 重点： 人体生物大分子和大分子体系的结构、功能、相互 作用及其同疾病发生、发展的关系 医学分子生物学 分子医学 Molecular Medicine

The greatest intellectual revolution of the last 40 years may have taken place in biology Can anyone be considered educated today who does not understand a little about molecular biology? -F. H. Westheimer(Harvard University)

The greatest intellectual revolution of the last 40 years may have taken place in biology. Can anyone be considered educated today who does not understand a little about molecular biology? ─F. H. Westheimer (Harvard University)

Molecular medicine Molecular medicine is a broad field, where physical, chemical, biological and medical techniques are used to describe molecular structures and mechanisms, identify fundamental molecular and genetic errors of disease, and to develop molecular interventions to correct them

Molecular medicine is a broad field, where physical, chemical, biological and medical techniques are used to describe molecular structures and mechanisms, identify fundamental molecular and genetic errors of disease, and to develop molecular interventions to correct them. Molecular Medicine

The Nobel Prize in Physiology or Medicine 2007 for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells photo: Tim Roberts/PR photo: The p Newswire, HHMI Association Limited Photo: Scanpix/Dan Sears Mario R capecchi Sir Martin J, Evans Oliver smithies ①1/3 of the prize ①1/3 of the prize ①1/3 of the prize USA United Kingdom USA University of Utah Cardiff University University of North Salt Lake City, UT, USA: Cardiff, United Kingdom Carolina at Chapel Hill Howard Hughes Medical Chapel Hill, NC, USA Institute

General strategy for gene targeting in mice Step 1 Gene targeting in ES cells r Inserted DNA- Vector neo/ HSV-tk 1. ES cell culture Homologous DNA DNA Embryonic stem (ES) Blastocyst 2. Construction of targeting vector cells are cultivated The vector contains pieces of DNA that are homolo from mouse pre- gous to the target gene, as well as inserted DNA which plantation embryos changes the target gene and allows for positive- blastocysts negat ES cells Transfection Ne selection 3. ES cell transfection The cellular machinery for homologous recombination allows the targeting vector enables the target vector to find and recombine with the target gene Vector ned/ HSV-tk Rare cell carrying Target gene Targ Positive-negative selection 4. Proliferation Homologous recombination of targeted Es cell Selection for presence of neo/ and absence of HSV-tk enriches targeted Pure population of ES cells ES cells carrying targeted gene Targeted gene

Step 2 From gene targeted Es cells to gene targeted mice 5. Injection of Es cells into blastocysts The targeted ES celis where they mix and form a mosaic The injected blastocysts are implanted are injected with the cells of the inner cell mass into a surrogate mother where they into blastocysts. from which the embryo develops, develop into mosaic embryos. Mosaic inner ell mass 6. Birth and breeding Born mosaic mice of mosaic mice The mosaic mice mate with normal mice to produce both gene targeted and nomal offspring Mosaic mouse d rmal mous ♀ 9 Gene targeted mice-called"knockout Normal mice mice when the targeted gene is inactivated c The Nobel Committee tor Physiolog or Medcine Hbstratom: Anka Rol

The Nobel Prize in Physiology ol Medicine 2008 for his discovery of for their discovery of human human papilloma immunodeficiency virus viruses causin g cervical cancer Klaus Ruschho仟f Springer Medizin Verla photo: Sakutin/SCANPIX photo: Magunia/SCANPIX Harald zur Hausen Francoise Barre Luc Montagnier senoussi ①1/2 of the O 1/4 of the O 1/4 of the France France German Cancer Regulation of Retroviral World Foundation for department, Instit Prevention Pasteur Paris, france