生命科学概论(1) 导论
An introduction to basic life sciences (BLS)
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Biological approaches for fighting human diseases
KE, Yuehai
柯越海
Zhejiang University, School of Basic Medical Sciences (ZJBMS)
浙江大学基础医学院
Personal Profile
http://mypage.zju.edu.cn/yke
生命科学概论 (秋冬学期、开课代码 18122780) 责任主讲教师 (自2012- 迄今）
课件下载：教学进度（适用于16年秋冬学期）导论 、生命的细胞基础 、人类学
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Overviews
1. About life sciences
2. About this curriculum
3. History of life sciences: Biological approaches
for fighting human diseases
Basic properties for living organisms
1.
2.
3.
4.
5.
6.
7.
Order (form)
Regulation
Growth and development
Energy processing
Response to environment
Reproduction
Evolutionary adaption
From biology to life sciences
Biology: the study of living
organisms, including their structure,
function, growth, origin, evolution,
distribution, and taxonomy
Life sciences: is interdisciplinary
fields living organisms and how
they interact with their
environments, also involving
technological advances.
Living organisms interacting with their
environments
Ecosystem is a community of living organisms (plants, animals and microbes)
in conjunction with the nonliving components of their environment (things
like air, water and mineral soil), interacting as a system
Will man conquer nature? 人能胜天吗？
Biotechnological advances
bio—the use of biological processes; and
technology—make useful products and solve problems
Dolly Sheep
from biotechnology to bioindustry and
biobusiness
Our teaching scope and focuses for BLS
• Life sciences: is interdisciplinary fields living organisms and how
they interact with their environments, also involving technological
advances.
• Basic Life Sciences (BLS): A full overview of the basic principles of
life sciences, emphasizing the life hierarchy of organization at
levels, continuous evolutionary processes by which diverse
organisms develop.
Life’s hierarchy of organization:
from global to microscopic scale
−Biosphere
−Ecosystem
−Community
−Population
−Organism
−Organ
−Tissue
−Cell
−Organelle
−Molecule
Extended readings
Life’s hierarchy of continuous evolution
The hierarchy of life
classification
from virus to human
Three domains of life
•Archaea (古生菌界)
•Bacteria (细菌界)
•Eukaryote (真核界)
Evolution explains the unity and diversity of life
Subphylum Vertebrata （脊椎动物亚门）
1. Jawless Fishes （无颌纲鱼形动物）; Cartilage Fishes （软骨鱼
纲）; Bony Fishes （硬骨鱼纲）; 4. Amphibians （两栖纲）;
Reptiles （爬行纲）; Birds （鸟纲）; Mammals （哺乳纲）
哺乳纲灵长目人科人属现代智人种
Human Origins: multiregional vs. “Outof-Africa” origin
“Mitochondrial Eve" and "Y Chromosome Adam”
What is Anthropology?


Anthropology = Anthropos（人） + logos
（科学）
is the scientific study of humans, past and
present, that draws and builds upon
knowledge from the social sciences and life
sciences, as well as the humanities.
1948年，吴定良教授当选国民政府中央研
究院第一任院士，并受浙江大学校长竺可
桢教授的邀请调至浙江大学，在浙江大学
成立了人类学系和人类学研究所。
1950年，第一届中国人类学学会会员
在杭州西湖留影。
1.
About life sciences?
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Living organisms, Environments and biotechnology
Basic features of life
Life’s hierarchy: organization and evolution
2.
About this course
−
Lecturers
−
Syllabus
−
Textbook and Reference
−
Teaching website
3.
History of life sciences: Biological approaches for fighting human
diseases
BLS Lecturers
柯越海
教授、博导
程洪强
副教授、博导
蒋萍萍
张雪
副教授、博导
副教授、博导
浙江大学基础医学院
研究方向：分子医学
浙江大学基础医学院
研究方向：分子医学
浙江大学医学院
研究方向：遗传学
浙江大学基础医学院
研究方向：分子医学
联系方式：
Tel：88206607
13905719900
Email：[email protected]
联系方式：
Tel：88208583
Email：[email protected]
联系方式：
Tel： 88982356
联系方式：
Tel：88208583
Email：[email protected]
Email： [email protected]
基本教学理念
三个衔接(高中-大学、中文-英文、生物与医学）
课程教学与自学相结合，提高自我导向学习能力
引导式教学、启发式教学、建构式教学
举例：《生命科学基础.动物学》 比较解剖与系统进化
Heart Evolution
www.bms.zju.edu.cn
举例：《生命科学基础.呼吸系统》
举例：《生命科学基础.免疫》
NgAgo
CRISPR/Cas9
Assessment
Final mark (100%)
−Essay: 30%
−Final Exam (choices, reviewing questions) :70%
1.
About life sciences
−
−
−
Living organisms, Environments and biotechnology
Basic features of life
Life’s hierarchy: organization and evolution
2.
About this curriculum
−
Lecturers
−
Syllabus
−
Textbook and reference
−
Teaching website
3.
History of life sciences (1859- current) : Biological approaches for
fighting human diseases
History of life sciences
•
(1859-1953): Classic biology
•
(1953-2003)：Molecular biology
era
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•
Evolutionary biology
Zoology
Plant
Microbiology
Biochemistry
Genetics
Cell biology…
Molecular genetics
Molecular cell biology
Genomics…
(2003- Current)：PostGenomics/Omics era/New
biology/Big Data
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Variation and Regulation
System biology
Functional genomics
Bioinformatics
Biomedical sciences
Translational research…
“On the origin of Species” (1859)
He established that all species of life have descended over
time from common ancestors, and proposed the scientific
theory that this branching pattern of evolution resulted
from a process that he called natural selection.
Charles Darwin
(1809 – 1882)
“father of biology”
David Duncan Main
（1856-1934）
In modified form, Darwin's scientific discovery is the
unifying theory of the life sciences, explaining the
diversity of life.
Darwin as a medical student at University of Edinburgh
传承历史的浙大医学
浙江大学-求是书院 （1897）
林启
（1839 - 1900）
广济私立医学专科学校 （1881-1926）
梅藤更博士
仁医、仁术、仁心… ..
www.bms.zju.edu.cn
•
“On the origin of Species” (1859)
“father of genetics” (1865)
Mendel's first laws: the law of segregation (3:1)
Mendel's second laws: Law of Independent Assortment (9:3:3
Gregor Mendel
(1822 - 1884)
1) Alternative versions of genes account for variations in inherited
characteristics
2) For each characteristic, an organism inherits two alleles, one from each
parent.
3) The two alleles for each characteristic segregate during gamete production.
• One Gene-One enzyme (polypeptide) Hypothesis (1941)
• In 1941, George Beadle and Edward Tatum proposed the one gene-one
enzyme theory.
George Wells Beadle Edward Lawrie Tatum 1. Proteins are the products of genes.
2. Proteins catalyze biochemical reactions.
(1903-1989)
(1903-1975)
3. Such reactions produce phenotypes, either directly or
indirectly.
4. Different alleles produce different phenotypes
In 1959 Tatum revised as the one gene, one polypeptide chain hypothesis.
Some proteins are composed of different polypeptide chains encoded by separate genes,
so the hypothesis now holds that mutation in a gene encoding a specific polypeptide can
alter the ability of the encoded protein to function and thus produce an altered phenotype.
One Gene-One enzyme (polypeptide) Hypothesis
Neurospora crassa： Nutritional mutation experiments
One Gene-One enzyme (polypeptide) Hypothesis
One Gene-One enzyme (polypeptide) Hypothesis
• First identification DNA as genetic materials
(1944)
Fred Griffith
(1897-1941)
(1928) Fred Griffith worked with 2 strains of Pneumonia causing bacteria Smooth strain
(Virulent S) slime capsule (not seen by immune system and kills mice) and Rough strain
(Nonvirulent R) no capsule (easily killed)
He found that R strain could become VIRULENT when it took in DNA from heat-killed S strain
His Study suggested that DNA was probably the genetic material
Posthumous Identification of Griffith's Transforming Principle (1944)
• Structure of DNA (1953)
 (1951) Rosalind Franklin took diffraction x-ray
photographs of DNA crystals
 In the 1950’s, Watson & Crick built the first model
of DNA using Franklin’s x-rays
James Watson
(1928- )
& Francis Crick
(1916-2004)
Eagle Pub, Cambridge
History before 1953
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(1859)“On the origin of Species”
(1860) Gregor Mendel Mendel’s law, and was rediscovered in 1900
(1869) First isolation of DNA
(1903) Sir Archibald Garrod, First suggest a genetic cause for enzymatic
errors of metabolism
(1928) Fred Griffith, First identification DNA as genetic materials, was
rediscovered 1944
(1933) Thomas Hunt Morgan Law Linkage and Crossing Over Between
Genes.
(1941) George Beadle and Edward Tatum proposed the one gene-one
enzyme theory
(1953) James Watson & Francis Crick, Double helix of DNA
Molecular biology begins...
 (1958) Francis Crick proposed central dogma of molecular Biology
 (1958) F. Sanger & colleagues, first protein sequence (1958 Nobel prize)
 (1966) R. Holly，H. G. Khorana & M. Nirenberg discovered genetic codon (1968 Nobel
prize). They demonstrated that a sequence of three nucleotide bases (a codon)
determines each of 20 amino acids.
 (1970) W. Arber, D. Nathans, & H. O. Smith, Restriction endonucleases discovered (1978
Nobel prize)
 (1972) Paul Berg created the first recombinant DNA molecule. (1980 Nobel prize) . Paul
Berg isolated and employed a restriction enzyme to cut DNA. Berg used ligase to paste
two DNA strands together to form a hybrid circular molecule. This was the first
recombinant DNA molecule.
 (1977) Fred Sanger (UK) independently develop methods for sequencing DNA. (1980
Nobel prize)
 (1985) Kary B Mullis developed PCR methods (1993 Nobel prize)
 (1990) Human Genome Project begins
 (1997) Clone sheep (1997)
 (2003) HGP was complete，Post-genomics (-omics, signal regulation, translational
medicine)
Central dogma of molecular biology （1958）
Francis Crick
(1916-2004)
Central dogma of biology : from genotype to phenotype
Central dogma of Molecular Biology
Basic Concepts of Genetics
•One center: Central dogma
(from genotypic variation to phenotypic
variation)
•Two basic elements: genetic and environmental effects
•Three levels: cell, individual and population
1. About this course
2. History （Before 1953）
3. The era of molecular biology: current trends
I. Central dogma (1958)
II. Genomics and HGP (1990-2003)
III. Post-genomics (2003- )/ New Biology (2012- )
Human Genome Project (1990)
Goals of the Human Genome Project (HGP) were to:
 Construct maps of the genome (genetic and physical)
 Identify all the genes (now known to be about 30,000)
 Determine the entire DNA sequence (3,000,000,000 bp)
 Technology development
 Model organism genome projects (E. coli, yeast, mouse, fruit fly, C.
elegans)
 Ethical, legal and societal implications (ELSI)
Francis Collins
(1950- )
Craig Venter
(1946- )
Progress made by Human Genome Project
 identify all the approximately 25,000-30,000 genes in human DNA,
 determine the sequences of the 3 billion chemical base pairs that make up
human DNA,
 store this information in databases,
 improve tools for data analysis,
 transfer related technologies to the private sector
 address the ethical, legal, and social issues (ELSI) that may arise from the
project.
 the total number of genes is estimated at around 30,000--much lower than
previous estimates of 80,000 to 140,000.
 almost all (99.9%) nucleotide bases are exactly the same in all people.
例题分析：思考题
有研究显示人类基因数量可能比虫还少，在20世纪60年代时，科学家就预测人类
基因组至少含有200万个编码蛋白质的DNA序列。不过随着科学的发展，这个预
测的数字越来越小，最新的一份研究报告表明人类基因组里只有不到1.9万编码蛋
白的基因，这一数字甚至比线虫还要小。此前的一系列的研究已经证明并不是越
复杂的生物体拥有越多的基因。据报道，某类水蚤有3.1万基因，是动物界之最。
但它还不是最多的，日本一种开花植物衣笠草（Paris japonica）是最多基因记
录的保持者，大致1490亿个碱基对。请根据本学期学习的基因组遗传与变异
相关知识，如何理解这个生物学现象？
Post-genomics: Variation and Regulation
HapMap project (Haplotype Map)
officially started 2002
• In the first phase genotyped
1.1 million SNPs in 269
individuals from four ethnic
origins.
• Second phase will genotype
another 4.6 million SNPs.
HapMap
Chart genetic variation
within the human genome
• Goal was to find most SNPs
that occur with frequencies
of at least 5% in the human
population.
Omics era began…
Post-genomics: Variation and Regulation
Typical intracellular communication
(pathway/cascade/molecular events/networking/activities)
First messagers->Receptors->Secondary messagers->Responses
Chemical modification of signal protein
•
•
•
•
•
•
Phosphorylation
Methylation
Ubiquitination
Sumoylation
Glycosylation
Acetylation
A ubiquitous regulatory mechanism in
control of molecular events
Signal regulation and networking
A power tool for understanding human diseases
1. Biomarkers for Diagnosis and Prognosis
2. Targets for Therapy and Interference
Translational medicine (转化医学)
 To translate Biomedical discoveries into promising new diagnostic tests,
therapies and medications.
 To accelerate the process which leads from evidence-based medicine to
sustainable solutions for public health problems
Bench
Bedside
Community
Seeking a new solutions to accelerate the Bench to Bedside (B-2-B)
and Bench to Community translations (B-2-C).
2003 Science
Elias Zerhouni
Director of NIH
To improve human health, scientific discoveries
must be translated into practical applications. Such
discoveries typically begin at “the bench” with
basic research — in which scientists study disease
at a molecular or cellular level — then progress to
the clinical level, or the patient's “bedside.”
Molecular approaches for translational medicines
Omics and Systems Biology
Systems genetics seeks to understand this complexity by integrating the
questions and methods of systems biology with those of genetics to solve the
fundamental problem of interrelating genotype and phenotype in complex
traits and disease.
A broad discipline of science and
engineering for analyzing the
interactions of biological
information objects in various omics.
• Mapping information objects
such as DNA, RNA and Proteins;
• Finding interaction
relationships among the objects;
• Engineering the networks and
objects to understand and
manipulate the regulatory
mechanisms;
Evolving System Biology
Systems Biology and Precision Medicine
Promise of personalized omics to precision medicine
Summary
Thank you for your time
 About life sciences
−Basic features of living organisms
−Living organisms, environments and biotechnology
−Life’s hierarchy: organization and evolution
 About this curriculum
−Lecturers, Syllabus, Textbook and Reference, Teaching website, Assessment
 History of life sciences: Biological approaches for fighting human diseases
−History （Before 1953）:
Gregor Mendel, Hunter Morgan, C.C. Tan,
George Beadle and Edward , Fred Griffith,
James Watson & Francis Crick
−The era of molecular biology: current trends
−Central dogma (1958)
−Genomics and HGP (1990-2003)
−Post-genomics (2003- )/ New Biology (2012- )
−Genomic diversity and -Omics
−Signal regulation and networking
−Translational medicine
−System biology and Big Data/New Biology
− Promise of personalized omics to precision medicine