《Molecular cell Biology》课程教学大纲

一、课程基本信息

二、课程目标

（一）总体目标：

（以三维目标即知识与技能、过程与方法、情感态度与价值观的形式反映核心素养观念和内容，其中核心素养不仅关注学生“当下发展”，更关注学生“未来发展”所需要的正确价值观念、必备品格和关键能力，即把知识、技能和过程、方法提炼为能力，把情感态度、价值观提炼为品格）（五号宋体）

This course is designed for the sophomore in college of Pharmaceutical Sciences, Soochow University. Students are encouraged to take General Chemistry, Organic Chemistry, and Biochemistry courses before taking this course.

This course will teach a variety of topics including cell structures and functions, the central dogma of biology, techniques in molecular biology, transportation of materials through biomembrane, protein trafficking, vesicle transport, cell signaling, cell differentiation and cell death, etc.

The objective of the course is to help students to understand the advanced principles in molecular biology, cell biology, and cell signaling. After taking this course, the students should be able to know the major principles and techniques in the above fields. They should also be able to use these techniques for their thesis work.

（二）课程目标：

（课程目标规定某一阶段的学生通过课程学习以后，在发展德、智、体、美、劳等方面期望实现的程度，它是确定课程内容、教学目标和教学方法的基础。）（五号宋体）

课程目标1：

1.1 To learn the cell structures and functions, the central dogma of biology, and techniques in molecular biology

1.2 To understand the different ways and models for the transportation of materials through biomembrane, protein trafficking, and vesicle transport.

1.3 To know the major signaling pathways in cell signaling, cell differentiation and cell death.

课程目标2：

2.1 To improve reading, listening, writing in English.

2.2 To learn course materials in English.

2.3 To improve the communication skills in English.

（要求参照《普通高等学校本科专业类教学质量国家标准》，对应各类专业认证标准，注意对毕业要求支撑程度强弱的描述，与“课程目标对毕业要求的支撑关系表一致）（五号宋体）

（三）课程目标与毕业要求、课程内容的对应关系（小四号黑体）

表1：课程目标与课程内容、毕业要求的对应关系表 （五号宋体）

（大类基础课程、专业教学课程及开放选修课程按照本科教学手册中各专业拟定的毕业要求填写“对应毕业要求”栏。通识教育课程含通识选修课程、新生研讨课程及公共基础课程，面向专业为工科、师范、医学等有专业认证标准的专业，按照专业认证通用标准填写“对应毕业要求”栏；面向其他尚未有专业认证标准的专业，按照本科教学手册中各专业拟定的毕业要求填写“对应毕业要求”栏。）

三、教学内容（四号黑体）

Chapter 1. Cell structure and function（应征）

1. 教学目标 （五号宋体）

• Make a brief introduction of molecular cell biology

• Understand the relationship cell biology and molecular biology

• Understand the morphology of intracellular organelles

• Understand the basic functions of intracellular organelles

2. 教学重难点

教学重点:

• Organisms and virus

• Prokaryotic and eukaryotic cells

• The function and localization of various intracellular compartments

教学难点:

• Membrane contact sites between different organelles

• The similarity and difference between non-dividing and dividing cells

3. 教学内容

1-1 Brief review of the living organisms.

 All living organisms descended from a common ancestral cell

 The general location and forms of the genome in cells and viruses

 The size of virus, prokaryotic and eukaryotic cells

1-2 Discuss the difference between the virus and living organisms.

 A virus is not a living organism

 A virus is a microscopic particle that can infect the cells of a biological organism

 The structure of naked virus and enveloped virus

 The origin of the virus: 3 major hypothesis

1-3 Introduce the cellular organelles

 The size of mitochondrion, ER, endosome, lysosome and proteasome in cells.

 Membrane contacts in cells: function and dynamics

 Membrane-less organelles and phase separation in cells

 The structure and function of non-neuronal and neuronal cells.

4. 教学方法

多媒体教学：

• Illustration of living organisms

• Illustration of cell structure

• Illustration of organelle morphology

• Illustration of the lipids and membrane proteins

互动教学：

• Does virus belong to the living organisms? Why?

• What happens if proteins cannot be degraded by the degradative systems?

• Is there any membrane-less organelle in the cell?

• How big are mitochondria?

5. 教学评价

课后问题：

• What are the similarities between mitochondria and bacteria?

• What are the differences between prokaryotic and eukaryotic cells?

• Why the virus is not a living organism?

• What are the differences between neuron and non-neuronal cell?

• What are the functions of membrane-less organelles?

Chapter 2. DNA replication, repair and recombination（滕昕辰）

1. 教学目标 （五号宋体）

• Understand the structure of DNA structure and how it affects the properties and functions of DNA

• Understandthe molecular mechanism and characteristics of DNA replication

• Understand how DNA replication can be extremely accurate.

• Understand the mechanism of generation of DNA mutations and DNA repair.

2. 教学重难点

教学重点:

• DNA structure: first order, second order, and third order

• Mechanism and characteristic of DNA replication

• Types of DNA mutations

• Mechanism of DNA repair

教学难点:

• Proofreading mechanism of DNA replication

• Different DNA repair systems

3. 教学内容

2-1 Structure of DNA

 Structure of nucleotides

 Differences between deoxyribonucleotides and ribonucleotides

 Terminology of nucleosides and nucleotides

 Structure of double-stranded DNA: double helix, Watson-Crick base pairs, opposite directionality

 Special properties of double-stranded DNA: reversible strand separation, supercoiled structure

2-2 DNA replication

 Properties of DNA replication: semiconservative, 5’3’, needs a primer, semidiscontinuous, bidirectional

DNA replication fork: leading strand, lagging strand

Replication origin(s) in prokaryotic and eukaryotic cells

 Proteins participating in DNA replication: DNA polymerase, helicase, primase, sliding clamp, clamp loader, topoisomerase, single-stranded DNA–binding protein, ribonuclease H, ligase

 Telomere and telomerase

2-3 DNA repair and recombination

Types of DNA mutations: point mutations, insert/deletion mutations, large-scale mutations

 Causes of DNA mutations: errors generated by DNA polymerase, chemical and radiation damages

Base excision repair (BER) eliminates damaged bases and T-G mismatches

 Mismatch repair (MMR) eliminates other base-pair mismatches and insertions or deletions of one or a few nucleotides

 Nucleotide excision repair (NER) targets large, bulky lesions that distort the normal shape of DNA locally

 Two ways to repair double-strand breaks: nonhomologous end joining & homologous recombination

4. 教学方法

多媒体教学：

• Illustration of DNA structure

• Illustration of detailed process of DNA replication

• Illustration of structure and function of key proteins involved in DNA replication

• Illustration of different types DNA mutations

• Illustration of different DNA repairs systems

互动教学：

• Ask the students to draw of the complementary DNA strand sequence of a given DNA strand.

• How many ways can DNA replicate? How can we prove this experimentally?

• Are primers needed for RNA replication?

• Can both strands of DNA replicate continuously? Why?

• What is the consequence of having only one replication origin per chromosome in eukaryotes?

• What are the problems with linear DNA replication?

• What happens if the insertion/deletion is not a multiple of three base pairs?

• Possible consequences of nonhomologous terminal recombination repair?

5. 教学评价

课后问题：

• What difference between RNA and DNA helps to explain the greater stability of DNA?

• What are Watson-Crick base pairs? Why are they important?

• What characteristic of DNA results in the requirement that some DNA synthesis be discontinuous?

• What is the proofreading mechanism in DNA replication?

• What is the function of the slide clamp? What is the consequence without the slide clamp?

• Describe the problem that occurs during DNA replication at the ends of chromosomes. How are telomeres related to this problem?

• What are the three excision-repair systems found in eukaryotes, and which one is responsible for correcting thymine-thymine dimers that form as a result of UV light damage to DNA?

• Briefly describe the similarities and differences of the two processes that can repair double-strand breaks.

Chapter 3. From DNA to protein（滕昕辰）

1. 教学目标

• Understand the basic processes and molecular mechanisms of transcription

• Understand the significance and molecular mechanisms of mRNA processing in eukaryotic cells

• Understand the decoding mechanism of mRNA by tRNAs

• Understand the basic processes and molecular mechanisms of protein translation

2. 教学重难点

教学重点:

• Fundamental processes and molecular mechanisms of RNA transcription

• Fundamental processes and molecular mechanisms of mRNA processing in eukaryotic cells

• The decoding of mRNA by tRNAs

• Structure and function of tRNA-aminoyl synthase

• Molecular mechanisms of initiation, extension, and termination of translation

教学难点:

• Sequence relationships of the template, coding strand and RNA transcripts

• RNA transcription initiation and abortive initiation

• Nonstandard base pairing between codons and anticodons

• Mechanism and significance of proofreading function of aminoyl-tRNA synthase

• Translocation of sites A, P, and E during protein translation

• Function of GTP-binding proteins involved in protein translation

3. 教学内容

3-1 The central dogma in prokaryotic vs. eukaryotic cells

3-2 Transcription of protein-coding genes and formation of functional mRNA

   Template DNA of transcription

   Properties of RNA synthesis: 5’3’, needs no primer

   Functions of three eukaryotic RNA polymerases, especially properties of Pol II

   Three stages in transcription: initiation, elongation, and termination

   Processing of eukaryotic pre-mRNA: 5’ capping, 3’ poly-adenylation, and RNA splicing

3-3 The decoding of mRNA by tRNAs

   Three RNAs involved in translation: mRNA, tRNA, rRNA

   Messenger RNA carries information from DNA in a three-letter genetic code

   The folded structure of tRNA promotes its decoding functions

   Nonstandard base pairing between codons and anticodons

   Function of aminoacyl-tRNA synthetases in decoding

3-4 Stepwise synthesis of proteins on ribosomes

   Structure of ribosomes: RNA components, A, P, E sites

   Stepwise synthesis of proteins on ribosomes: initiation, elongation, and termination

GTPase-superfamily proteins function in several quality-control steps of translation

4. 教学方法

多媒体教学：

• Illustration of RNA polymerase structure

• Illustration of three stages in transcription: initiation, elongation, and termination

• Illustration of eukaryotic pre-mRNA processing

• Illustration of decoding of mRNA by tRNAs

• Illustration of stepwise synthesis of proteins on ribosomes

互动教学：

• Is the proofreading function of RNA polymerase different from that of DNA polymerase?

• Why does RNA transcription tolerate a high error rate?

• Why is mRNA more stable when it is added a 5 'cap or a 3' poly-A tail?

• There are 61 codons, but how can many cells have less than 61 tRNAs?

• What is the proofreading mechanism of protein translation?

5. 教学评价

课后问题：

• What are the differences of central dogma between prokaryotes and eukaryotes?

• Can you write the mRNA sequence (or non-template DNA sequence) when given the template DNA strand sequence?

• What is the proofreading mechanism in RNA synthesis?

• How is eukaryotic pre-mRNA processed?

• What differences can you identify between DNA synthesis and RNA synthesis?

• What are the proofreading mechanism in protein synthesis?

• What are the functions of A, P, E sites in ribosomes during translation?

• What are the functions of GTP-biding proteins in translation?

Chapter 4. Genes, genomics and chromosomes（滕昕辰）

1. 教学目标

• Understand the structure of genes and all the functional elements within a gene

• Be able to identify single genes, gene families, and pseudogenes

• Be able to understand the influence of various non-coding DNA on genome formation

• Understand how DNA is folded step by step to form the higher structure of chromosomes

• Understand the effect of histone tail modification on chromosome structure and transcription

2. 教学重难点

教学重点:

• Structure of genes and all the functional elements within a gene

• Structure of chromosomes

• Differences of gene structure and chromosome structure between prokaryotic and eukaryotic cells

• Composition of human genome

教学难点:

• Differences of gene structure between prokaryotic and eukaryotic cells

• Modification of histone and structure of chromosome

• Non-coding DNAs in human genome

3. 教学内容

4-1 Molecular definition of a gene

4-2 Structure of genes in prokaryotic cells

   Structure of operons: promoter, operator, structural genes

   Structure of chromosomes in prokaryotic cells

4-3 Structure of genes in eukaryotic cells

Simple eukaryotic transcription unit

 Complex eukaryotic transcription unit containing alternative splicing sites, poly(A) sites, or promoters

 Organization of genes on chromosomes

 Protein-coding genes may be solitary or belong to a gene family

 Heavily used gene products are encoded by multiple copies of genes

 Non-protein coding genes encode functional RNAs

4-4 Non-coding DNA in eukaryotic cells

   Simple-sequence DNAs: Microsatellites

   Interspersed repeats: DNA Transposons, retrotransposons (LTRs, Non-LTRs (LINEs, SINEs))

4-5 Structural organization of eukaryotic chromosomes  

 Chromatin exists in extended and condensed forms         

 Modification of histone tails control chromatin condensation and function

 Functional elements of eukaryotic chromosomes: replication origins, centromere, telomere

4-6 Structure of mitochondrial genome

4. 教学方法

多媒体教学：

• Illustrations of differences between the prokaryotic and eukaryotic cells

• Illustrations of structure of genes and chromosomes in prokaryotic and eukaryotic cells

• Illustration of mechanism of transposons

• Illustration of structure of chromosome

互动教学：

• A prokaryotic operon can be transcribed into how many transcription units, how many proteins?

• What is the physiological significance of complex transcription units in eukaryotes?

• What kind of genes need multiple copies?

• Can transposons cause severe mutations?

• Between the loose and compact chromosome, which one is easier to be transcribed?

5. 教学评价

课后问题：

• What are the differences of gene structure between eukaryotes and prokaryotes?

• Can you give a big picture of the human genome compositions?

• Describe the differences between solitary genes, gene families, pseudogenes, and tandemly repeated genes.

• How is the repetitious DNA useful for identifying individuals by the technique of DNA fingerprinting?

• What is a nucleosome? What role do histones play in nucleosomes?

• How do chromatin modifications regulate transcription? What modifications are observed in regions of the genome that are actively transcribed and not actively transcribed?

• How would a chromosome be affected if it lacked (a) replication origins or (b) a centromere?

• Can proteins be synthesized inside mitochondria? Are all the mitochondrial proteins synthesized within mitochondria?

Chapter 5. Control of gene expression（滕昕辰）

1. 教学目标 （五号宋体）

• Understand the mechanism of gene transcription regulation in prokaryotes

• Understand the mechanism of gene transcription regulation in eukaryotes

• Understand the mechanism of post-transcriptional gene control in eukaryotes

2. 教学重难点

教学重点:

• Sigma factor

• lac operon, trp operon

• Multiple transcription-control elements

• Structure, functions and regulation of transcription factors

• Post-transcriptional regulation of gene expression

教学难点:

• Two-component regulatory systems in bacteria

• Molecular mechanism of transcription repression and activation

• Function of enhanceosome and mediator

• RNA interference

3. 教学内容

5-1 Gene expression regulation in bacteria

   Transcription initiation by bacterial RNA polymerase requires association with a Sigma factor

   Regulation of transcription initiation of lac operon

   Regulation of transcription initiation of Trp operon

   Regulation of transcription elongation and termination of Trp operon

   Riboswitch controls transcription termination

5-2 Transcriptional control of gene expression in eukaryotes

 Regulatory elements in eukaryotic DNA: RNA polymerase II core promoters (binding site for general transcription factor), promoter-proximal elements and enhancers (bindings sites for specific transcription factors)

 Function of general transcription factors

 Structure of specific transcription factors (homeodomain, zinc-finger, leucine-zipper, basic helix-loop-helix proteins)

 Transcription factor interactions increase gene-control options

 The mediator complex forms a molecular bridge between activation domains and Pol II

 Molecular mechanisms of transcription repression and activation

 Regulation of transcription factor

 Transcription Initiation by Pol I and Pol III

5-3 Post-transcriptional gene control in eukaryotes

 Regulation of pre-mRNA processing (alternative splicing)

 Transport of mRNA across the nuclear envelope

 Degradation of mRNAs in the cytoplasm occurs by several mechanisms

 RNA interference induces Degradation of mRNA

 Cytoplasmic polyadenylation promotes translation of some mRNAs

 Protein synthesis can be globally regulated (TORC1, eIF2 kinases)

4. 教学方法

多媒体教学：

• Illustration of structure and function of sigma factors

• Illustration of mechanism of operon regulation in bacteria

• Illustration of regulatory elements in eukaryotic cells

• Illustration of mechanism of transcription regulation in eukaryotic cells

• Illustration of mechanism of post-transcriptional regulation in eukaryotic cells

互动教学：

• Why do single-celled prokaryotes control gene expression at specific times?

• What happens if there is no mediator complex?

• Can alternative splicing of mRNA explain the differences between different tissues and cells?

• Is there directivity in the nucleation of mRNA? How to prove this experimentally?

• Why do the same genomes produce different proteomes?

• Why can a single fertilized egg cell become a variety of cell types?

• Can you predict the application of RNA interference?

5. 教学评价

课后问题：

• Describe the molecular events that occur at the lac operon when E. coli cells are shifted from a glucose-containing medium to a lactose-containing medium.

• Describe three types of post-transcriptional regulation of protein-coding genes.

• Why there are about 20000 genes in human but only ~1400 transcriptional factors?

• Describe the structural features and function of transcription activator and repressor proteins.

• How can transcription factors binding onto enhancers thousands of base pairs from the transcription start site affect the transcription initiation?

• How are transcriptional factors regulated by extracellular signals?

• Why there are much more proteins than genes in eukaryotic cells?

• What are the differences between miRNAs and siRNAs?

• List all the reasons you can think of to explain decreased expression of a protein.

Chapter 6. Molecular genetic technologies（滕昕辰）

1. 教学目标

• Understand the principle and procedure of DNA recombination technology

• Understand the construction methods and applications of genomic library and cDNA library

• Understand the method and application of mRNA level determination

• Understand the expression, purification, structure and function study of proteins

• Be able to select appropriate gene knockdown, knockout or editing methods according to experimental purposes

• Be able to understand the ethical consequences of human genetic modification

2. 教学重难点

教学重点:

• Materials and procedures for DNA recombination

• Construction and application of genomic and cDNA libraries

• Detection of mRNA expression

• Study of protein structure and function

• Genetic manipulation methods

教学难点:

• Principles of DNA sequencing

• Yeast two-hybrid screen

• Microarray analysis

• CRISPR-Cas9 gene editing system

3. 教学内容

6-1 DNA cloning by recombinant DNA methods

 Structure of plasmid vectors for cloning

 Restriction enzymes and DNA ligases allow insertion of DNA fragments into cloning vectors

 The polymerase chain reaction (PCR) amplifies a specific DNA sequence

 Cloned DNA molecules can be sequenced rapidly by methods based on PCR

6-2 Using cloned DNA fragments to study gene expression

 E. coli expression systems can produce large quantities of proteins from cloned genes

 Plasmid expression vectors can be designed for use in animal cells

 Cellular localization of tagged proteins expressed from cloned genes

 Yeast genomic libraries can be constructed with shuttle vectors and screened by functional complementation

 Yeast two-hybrid can be used to screen for protein binding partners

 Hybridization techniques permit detection of specific DNA fragments and mRNAs

 DNA microarrays can be used to evaluate the expression of many genes at one time

6-3 Inactivating the function of specific genes in eukaryotes

 Normal yeast genes can be replaced with mutant alleles by homologous recombination

 RNA interference causes gene inactivation by destroying the corresponding mRNA

 Specific genes can be permanently inactivated in the germ line of mice

 Gene editing methods: TALEN, TALE, CRISPR-cas9

4. 教学方法

多媒体教学：

• Illustration of structure and essential elements of a plasmid vector for cloning

• Illustration of procedure of molecular cloning

• Illustration of DNA sequencing principle

• Illustration of RNA detection

• Illustration of methods studying protein structure and function

• Illustration of gene manipulation methods

互动教学：

• How to link the pieces of DNA together?

• How to select the restriction enzymes?

• Is functional complementation suitable for dominant mutation?

• How to ensure that an exogenous gene introduced into a mammalian cell is passed on from generation to generation?

• Ethical consequences of gene editing?

5. 教学评价

课后问题：

• How complementation analysis can be used to reveal whether two mutations are in the same or in different genes? Why complementation analysis will not work with dominant mutations?

• What is the difference between a cDNA library and a genomic DNA library?

• Why was the discovery of a thermostable DNA polymerase so important for the development of PCR?

• How can the foreign protein be modified to facilitate its purification?

• What is the advantage of expressing a protein in mammalian cells versus bacteria?

• What techniques might researchers use to find out which tissues express a particular gene?

Chapter 7. Protein structure and function（许国强）

1. 教学目标 （五号宋体）

• To understand the protein structures

• To know the principle and mechanism for protein folding

• To understand the function of enzyme and in the catalysis of biological reactions

• To learn how the protein functions are regulated

• To learn the methods and principles for protein purification, detection, and characterization

• To understand the principle of proteomics for the detection of complex protein mixtures

2. 教学重难点

教学重点:

• Principle and mechanism for protein folding

• The function of enzymes and how it fulfills its function

• The regulation of protein functions

• Methods and principles for protein purification, detection, and characterization

• Proteomics for protein identification

教学难点:

• Protein folding mechanism

• Enzymatic kinetics

• Protein modification and its role in the regulation of biological functions

• Principles for protein purification, detection, and characterization

• Proteomics

3. 教学内容

7-1 Hierarchical Structure of Proteins

 Primary Structures

 Secondary Structures

 Tertiary Structures

 Structural Motifs

 Domains Are Modules of Tertiary Structure

 Quaternary Structures and Supramolecular Complexes

 Protein Sequences, Structures, and Function

7-2 Protein Folding

 Planar Peptide Bonds Limit the Shapes into Which Proteins Can Fold

 The Amino Acid Sequence of a Protein Determines How It Will Fold

 Folding of Proteins in Vivo Is Promoted by Chaperones

 Protein Folding Is Promoted by Proline Isomerases

 Abnormally Folded Proteins Can Form Amyloids That Are Implicated in Diseases

7-3 Protein Binding and Enzyme Catalysis

 Specific Binding of Ligands Underlies the Functions of Most Proteins

 Enzymes Are Highly Efficient and Specific Catalysts

 An Enzyme’s Active Site Binds Substrates and Carries Out Catalysis

 Serine Proteases Demonstrate How an Enzyme’s Active Site Works

 Enzymes in a Common Pathway Are Often Physically Associated with One Another

7-4 Regulating Protein Function

 Regulated Synthesis and Degradation of Proteins Is a Fundamental Property of Cells

 The Proteasome Is a Molecular Machine Used to Degrade Proteins

 Ubiquitin Marks Cytosolic Proteins for Degradation in Proteasomes

 Noncovalent Binding Permits Allosteric, or Cooperative, Regulation of Proteins

 Phosphorylation and Dephosphorylation Covalently Regulate Protein Activity

 Ubiquitinylation and Deubiquitinylation Covalently Regulate Protein Activity

 Proteolytic Cleavage Irreversibly Activates or Inactivates Some Proteins

7-5 Purifying, Detecting, and Characterizing Proteins

 Centrifugation

 Electrophoresis

 Liquid chromatography

 Protein detection with antibodies

 Application of radioisotopes for the detection of biological molecules

 Mass Spectrometry for the detection of protein mass and sequence

 Protein primary structure determination

 Protein conformation determination

7-6 Proteomics

 Proteomics for the detection of complex protein mixtures

 Advanced MS techniques

4. 教学方法

多媒体教学：

• Illustration of four different levels of protein structures

• Show different protein motifs

• Illustrate the post-translational modifications

• Illustrate the methods and mechanism for protein purification, detection, and identification

互动教学：

• What is the primary structure of a protein?

• What is secondary structure?

• How to calculate pitch and translation?

• What can an enzyme do?

• How to isolate proteins in different organelles?

5. 教学评价

课后问题：

• What are the four levels of protein structures?

• What are the protein motifs?

• What are the factors affecting protein folding?

• How does an enzyme work?

• What are the post-translational modifications and what are their functions?

• How does protein ubiquitination regulate protein functions?

• What are the functions of proteolytic cleavages?

• What are the major methods and their principles for protein purification?

• What are the major methods for protein detection and the underlying mechanism?

• What are the major approaches for the detection and determination of protein sequence and conformation?

• How can a complex protein mixture be identified?

• What are the major mass spectrometry methods for proteomics studies?

Chapter 8. Biomembrane structure（许国强）

1. 教学目标 （五号宋体）

• To learn the structure of membranes and the basic function of membrane

• To know the cell structures and components

• To learn the membrane lipids

• To learn the structure and basic functions of membrane proteins

• To know the relationship between blood types and glycoproteins

• To learn the structures of four common detergents and their functions

• To know the basic principles in lipid biosynthesis

• To understand the cholesterol biosynthetic pathway

• To understand the mechanisms of transport of cholesterol and phospholipids between membranes

2. 教学重难点

教学重点:

• The structure of membranes and the basic function of membrane

• The structure and basic functions of membrane proteins

• The structures of four common detergents and their functions

• Basic principles in lipid biosynthesis

• Transport of cholesterol and phospholipids

教学难点:

• The structure and basic functions of membrane proteins

• The structures of four common detergents and their functions

• The basic principles in lipid biosynthesis

• Transport of cholesterol and phospholipids

3. 教学内容

8-1 The lipid bilayer: Composition and structural organization

 Drug Travels to the Site of Action

 Biomacromolecules: Polysaccharide, Protein (peptide), RNA or DNA, Lipid

 Cell Structure and Components: Cell Membranes, Components of Cell Membranes, Amphiphilicity, Structure of Phospholipids, Properties of Phospholipids, Characteristics of the Bilayer, The Membrane Bilayer, Properties of Phospholipid Bilayers, Formation of Phospholipid Bilayers, The Faces of Cellular Membranes, Variation in Biomembranes in Different Cell Types, Variation in Biomembranes in Different Cell Types

 Three Classes of Membrane Lipids: Phosphoglycerides, Sphingolipids, Sterols

 Gel-like and Fluid-like Forms of the Phospholipid Bilayer: Principles for Fluorescence Recovery after Photobleaching (FRAP), Lateral Movement of Proteins and Lipids within the Plasma Membrane, Lipid Components of Selected Biomembranes, Lipid Components in Exoplasmic and Cytosolic Leaflet are Different

 Lipid Components and Bilayer Thickness, Lipid Droplets Formation

8-2 Membrane proteins: Structure and basic functions

 Membrane Proteins are Responsible for Membrane Functions

 Proteins Interact with Membranes

 Type of Membrane Proteins: Integral Membrane Proteins, Lipid-anchored Membrane Proteins & Peripheral Membrane Proteins, Cytoskeletal Filaments

 Why are  Helices in Transmembrane Domains?

 Structure of Glycophorin A--a typical single-pass transmembrane protein, Structural Models of two multipass membrane proteins, Role of Charged Residues in the Assembly of Multimeric Membrane Proteins, Structural Model of One Subunit of OmpX, Covalently Link Hydrocarbon Groups to the Phospholipid Bilayer

 Orientation of Transmembrane Proteins and Glycolipids

 Blood Types vs Glycolipids Glycoproteins, Blood Types vs Serum Antibodies

 Lipid-binding Motifs Help Target Peripheral Proteins to the Membrane

 Structures of Four Common Detergents

 Solubilization of Integral Membrane Proteins by Non-ionic Detergents

 Detergents and Protein Solubility

8-3 Phospholipids, sphingolipids, and cholesterol: Synthesis and intracellular movement

 Basic Principles in Lipid Biosynthesis

 Fatty Acid–binding Protein (FABP)

 Phospholipid Synthesis in the ER Membrane

 Fatty Acids Are Assembled from Two-Carbon Building Blocks

 Cholesterol Biosynthetic Pathway

 Proposed Mechanisms of Transport of Cholesterol and Phospholipids between Membranes

4. 教学方法

多媒体教学：

• Use model and images to show the structure of membranes

• Illustrate the different membrane proteins to discuss the basic functions of membrane proteins

• Compare three classes of membrane lipids by describing their structures and the role in the formation of membranes

• Use table and structure to compare blood types and the difference in glycoproteins

• Compare the structures of four common detergents and analyze their roles and mechanism in protein solubilization

• Illustrate the synthesis of phospholipids, sphingolipids and cholesterol, and their intracellular transport

互动教学：

• How does drug travels to the site of action?

• What are the four biomacromolecules?

• What is the structure of phospholipids?

• What is the common nature of membrane lipids?

• What are the functions of membrane proteins?

• Why are  Helices the preferred structure in transmembrane domains?

• How do we distinguish different blood types?

5. 教学评价

课后问题：

• The lipid bilayer is often described as looking like a railroad track. Explain how the bilayer forms this structure.

• Biomembranes contain many different types of lipid molecules. What are the three main types of lipid molecules found in biomembranes? How are the three types similar, and how are they different?

• Lipid bilayers are said to behave like two-dimensional fluids. What does this mean? What drives the movement of lipid molecules and proteins within the bilayer? How can such movement be measured? What factors affect the degree of membrane fluidity?

• Why are water-soluble substances unable to freely cross the lipid bilayer of the plasma membrane? How does the cell overcome this permeability barrier?

• Proteins may be bound to the exoplasmic or cytosolic face of the plasma membrane by way of covalently attached lipids. What are the three types of lipid anchors responsible for tethering proteins to the plasma-membrane bilayer?

• What are detergents? How do ionic and non-ionic detergents differ in their ability to disrupt biomembrane structure?

• What are the common fatty acid chains in phosphoglycerides, and why do these fatty acid chains differ in their number of carbon atoms by multiples of 2?

Chapter 9. Transmembrane transport of ions and small molecules（许国强）

1. 教学目标 （五号宋体）

• To know the permeability of phospholipid bilayer to different solutes

• To understand the facilitated transport of glucose and water in cells

• To know the kinetics and model for glucose transport

• To understand the working models for typical ATP-powered pumps

• To learn how nongated ion channels work and how they distinguish very similar ions

• To know the methods to measure current flow through individual ion channels

• To understand the cotransport by symporters and antiporters and know typical examples

• To know the transcellular transport and typical examples

2. 教学重难点

教学重点:

• Permeability of phospholipid bilayer to different solutes

• Facilitated transport of glucose and its kinetics and working model

• The working models for typical ATP-powered pumps

• The working model for nongated ion channels and they specificity

• The methods to measure current flow through individual ion channels

• Cotransport by symporters and antiporters

• Transcellular transport

教学难点:

• The kinetics and working model of facilitated transport of glucose

• The working models for typical ATP-powered pumps

• The working model for nongated ion channels and they specificity

• Cotransport by symporters and antiporters

3. 教学内容

9-1 Overview of Transmembrane Transport

 Two Transport Directions

 Permeability of Phospholipid Bilayer

 Rate of Simple Diffusion across the Lipid Bilayer

 Effect of charge on diffusion rate

 Three Main Classes of Membrane Proteins Transport Molecules and Ions Across Cellular Membranes: Channels, Transporters, ATP-powered pump

 Multiple Membrane Transport Proteins Function together in the Plasma Membrane of Metazoan Cells

 Energy Source during Protein Transport

 Overview of Transmembrane Transport

9-2 Facilitated Transport of Glucose and Water

 Distinguish Uniport from Simple Diffusion

 Enzymatic Kinetics

 Rate of Transport

 Kinetics of Cellular Uptake of Glucose Mediated by GLUT Proteins

 Property for GLUT1 Transport

 Crystal Structure of the Human GLUT1 Uniporter across a Cellular Membrane

 A Working Model for GLUT1

 The Human GLUT Proteins

 How Is Water Transported? Osmotic Pressure π

 Aquaporins Increase the Water Permeability of Cellular Membranes

 Structure of an Aquaporin; Topology of a Single Aquaporin Subunit; Aquaporin 2 & Diabetes Insipidus

 Facilitated Transport of Glucose and Water

9-3 ATP-Powered Pumps and the Intracellular Ionic Environment

 Four Main Classes of ATP-Powered Pumps: P-class Pumps, V-class and F-class Pumps, ABC Superfamily Pumps

 Operational Model of the Ca²⁺ ATPase in the Sarcoplasmic Reticulum Membrane

 Steps in the Transport of Two Ca²⁺ to SR

 Structure of the Catalytic  Subunit of the Muscle Ca²⁺ ATPase

 Structure Similarities of the Membrane-Spanning Segments in the Na⁺/K⁺ ATPase and the Ca²⁺ ATPase

 Operational Model of the Plasma-Membrane Na⁺/K⁺ ATPase

 Effect of V-class Proton Pumps on H⁺ Concentration Gradients and Electric Potential Gradients across Cellular Membranes

 An in vitro Fluorescence Quenching Assay to Reveal the Phospholipid Flippase Activity of ABCB4: Procedure and Principles

 Function of the Cystic Fibrosis Transmembrane Regulator (CFTR) Cl^- Channel

 ATP-Powered Pumps and the Intracellular Ionic Environment

9-4 Nongated Ion Channels and the Resting Membrane Potential

 Structure of a Resting K⁺ Channel from the Bacterium Streptomyces lividans

 Mechanism of Ion Selectivity and Transport in Resting K⁺ Channels

 Patch Clamp to Measure Current Flow through Individual Ion Channels

 Patch-clamping Configurations

 Ion Flux through Individual Na⁺ Channels

 Oocyte Expression Assay for Patch Clamp

9-5 Cotransport by Symporters and Antiporters

 Transmembrane Forces Acting on Na⁺ Ions

 Na⁺-Linked Symporters Enable Animal Cells to Import Glucose and Amino Acids Against

 High Concentration Gradients

 Operational Model for the Two-Na⁺/One-Glucose Symporter

 Structure of the two-Na⁺/one-Leucine Symporter from the Bacterium Aquifex aeolicus

 Several Cotransporters Regulate Cytosolic pH

 CO₂ transport in Blood Requires a Cl⁻/HCO₃⁻ Antiporter

 Concentration of Ions and Sucrose by the Plant Vacuole

9-6 Transcellular Transport

 Transcellular Transport of Glucose from the Intestinal Lumen into the Blood

 Rehydration Therapy

 Acidification of the Stomach Lumen by Parietal Cells in the Gastric Lining

 Dissolution of Bone by Polarized Osteoclast Cells

4. 教学方法

多媒体教学：

• Use images and examples to show the permeability of phospholipid bilayer

• Illustrate the working model for facilitated transport, ATP-powered pumps, and nongated ion channels

• Use images to describe different catch-clamp settings to measure current flow

• Use examples to show the cotransport and transcellular transport

互动教学：

• Which small molecules can freely move through the phospholipid bilayer?

• What is the similarity and difference between cotransporters and ATP-powered pumps?

• Can GLUT1 transport molecules other than glucose?

• How to determine the activity of phospholipid flippase?

• Can a resting K⁺ channel transport sodium or calcium ions?

• Why are frog oocytes good model cells to perform catch-clamp experiments?

• What is the best drink for athletes to supply water quickly and efficiently (rehydration)?

5. 教学评价

课后问题：

• Which Molecules are Permeable to a Pure Phospholipid Bilayer?

• What are Three Main Classes of Membrane Proteins that Transport Molecules and Ions Across Cellular Membranes?

• What are the Three Types of Transporters?

• What are the ATP-powered pumps?

• What is the Difference between Different Transport Processes?

• How does GLUT1 Transport Glucose? (Use a Model to Describe)

• What are the Four Main Classes of ATP-Powered Pumps? What do they Transport?

• What are the Steps for a Ca²⁺ ATPase to Transport Ca²⁺ ions?

• How to Study the Phospholipid Flippase Activity?

• How does the Cystic Fibrosis Transmembrane Regulator (CFTR) Cl^- Channel Work?

• Why cannot Resting K⁺ Channels Transport Na⁺ and Ca²⁺?

• Why cannot Resting K⁺ Channels Transport Na⁺ and Ca²⁺?

• How to Measure Ion Current using Patch Clamp?

• What is the Operational Model for the Two-Na⁺/One-Glucose Symporter?

• Why do Drinks for Athletes Contain Sugar and Salt?

• What are the transporters working in the gastric lining?

Chapter 10. Moving proteins into membranes and organelles（许国强）

1. 教学目标 （五号宋体）

• To understand how proteins across the endoplasmic reticulum (ER) membrane

• To learn how membrane proteins are inserted into the ER

• To know the protein modifications, folding, and quality control in the ER

• To learn how proteins are localized to mitochondria and chloroplasts

• To understand the mechanism targeting proteins to peroxisome

• To understand how proteins are transport into and out of the nucleus

2. 教学重难点

教学重点:

• Proteins across the endoplasmic reticulum (ER) membrane

• Insertion of membrane proteins into the ER

• Protein quality control in the ER

• Proteins localization to the mitochondria and chloroplasts

• Proteins targeting to peroxisome

• Proteins transporting to and out of nucleus

教学难点:

• Mechanisms for protein transport and localization

• Insertion of membrane proteins into the ER

• Proteins localization to the mitochondria and chloroplasts

• Proteins targeting to peroxisome

• Proteins transporting to and out of nucleus

3. 教学内容

10-1 Targeting Proteins To and Across the ER Membrane

 Proteins must Reach their Correct Locations for Functioning

 Signal-based Targeting and Vesicle-based Trafficking

 Major Protein-Sorting Pathways in Eukaryotes

 Structure of the Rough Endoplasmic Reticulum

 A Hydrophobic N-Terminal Signal Sequence Targets Nascent Secretory Proteins to the ER

 Secretory Proteins Enter the ER Lumen

 Cell-free Protein Synthesis (CFPS)

 Translation and Translocation Occur Simultaneously

 Structure of the Signal Recognition Particle (SRP)

 Cotranslational Translocation

 Sec61 is a Translocon Component; Structure of an Archaeal Sec61 Complex

 Post-translational Translocation

10-2 Insertion of Membrane Proteins into the ER

 Types of ER Membrane Proteins

 Classes of ER Membrane Proteins

 Membrane Insertion and Orientation of Type I Transmembrane Proteins

 Membrane Insertion and Orientation of Type II Transmembrane Proteins

 Membrane Insertion and Orientation of Type III Transmembrane Proteins

 Insertion of Tail-anchored Proteins

 Topogenic Sequences Determine the Orientation of ER Membrane Proteins

 GPI-anchored Proteins

 Hydropathy Profiles from Protein Sequences

 The Topology of a Membrane Protein Can Often Be Deduced from Its Sequence

10-3 Protein Modifications, Folding, and Quality Control in the ER

 Biosynthesis of Oligosaccharide Precursors

 Addition and Initial Processing of N-linked Oligosaccharides

 Action of Protein Disulfide Isomerase (PDI)

 Illustration of Anfinson’s Experiments; What Happens in Anfinson’s Experiment?

 Hemagglutinin Folding and Assembly

 Trimers of HA Protein from the Surface of the Viral Membrane

 Peptidyl-prolyl Isomerases for Protein-Folding

 The Unfolded-Protein Response (UPR)

 Modifications of N-linked Oligosaccharides are used to Monitor Folding and for Quality Control

10-4 Targeting of Proteins to Mitochondria and Chloroplasts

 Targeting Sequences That Direct Proteins from the Cytosol to Organelles

 Amphipathic N-Terminal Targeting Sequences Direct Proteins to the Mitochondrial Matrix

 Cell-free System to Assay the Import of Mitochondrial Precursor Proteins

 Protein Import into the Mitochondrial Matrix

 Mitochondrial Protein Import Processes

 Targeting Sequences in Imported Mitochondrial Proteins

 Three Pathways to the Inner Mitochondrial Membrane from the Cytosol

 Two Pathways to the Mitochondrial Intermembrane Space

 Transporting Proteins to Chloroplast Thylakoids

10-5 Targeting of Peroxisomal Proteins

 PTS1-directed Import of Peroxisomal Matrix Proteins

 Different Pathways for Incorporation of Peroxisomal Membrane and Matrix Proteins

 Model of Peroxisomal Biogenesis and Division

10-6 Transport Into and Out of the Nucleus

 Nuclear Pore Complex at Different Levels of Resolution

 Nuclear-localization Signals (NLSs) Direct Proteins to the Cell Nucleus

 Cytosolic Proteins are Required for Nuclear Transport

 Mechanism for Nuclear Import of Proteins

 Ran-dependent and Ran-independent Nuclear Export

4. 教学方法

多媒体教学：

• Use pathways to show how proteins are transported after synthesis

• Use diagram to show how proteins are localized to different organelles

• Use illustration to show the post-translational modification and conformational changes during protein folding

• Use fluorescence images to demonstrate the localization of proteins in cells

• Use recently published papers for supplementary reading

互动教学：

• Where are proteins synthesized?

• How to determine the signal sequence from a protein sequence in a protein database?

• What is the cell-free protein synthesis system?

• At which codons does protein synthesis start and end?

• What are the functions of disulfide bonds?

• Which sequence determines the localization of a nuclear protein?

5. 教学评价

课后问题：

• What are the Two Major Protein-Sorting Pathways in Eukaryotes?

• What is the Signal-based Targeting for Protein Transport?

• What is Secretory Pathway?

• What are the Characteristics of a Hydrophobic N-Terminal Signal Sequence Targeting Nascent Secretory Proteins to the ER?

• What is Cotranslational Translocation?

• What are the Main Steps for Cotranslational Translocation?

• What is Post-translational Translocation?

• What are the Major Steps for Post-translational Translocation?

• What are the Six Classes of ER Membrane Proteins?

• How do Different Types of Membrane Proteins Insert and Orient?

• What is the Similarity and Difference between Type II and Type III Transmembrane Proteins?

• How do Topogenic Sequences Determine the Orientation of ER Membrane Proteins?

• What is Hydropathy Profile?

• What are the Possible Protein Modifications in ER?

• What are the Roles of Protein Disulfide Isomerase (PDI)?

• What is the Unfolded-Protein Response (UPR)?

• What are Targeting Sequences That Direct Proteins from the Cytosol to Organelles

• What are the Properties for the N-Terminal Targeting Sequences that Direct Proteins to the Mitochondrial Matrix?

• What are the Major Steps for Protein Importing into the Mitochondrial Matrix?

• Are Cytosolic Proteins Required for Nuclear Transport?

• Which Sequences are Required for Nuclear Import or Nuclear Export?

Chapter 11. Vesicular traffic, secretion, and endocytosis（许国强）

1. 教学目标 （五号宋体）

• To know the techniques for studying the protein secretory pathway

• To understand the molecular mechanisms of vesicle budding and fusion

• To know the sorting signals that direct proteins to specific transport vesicles

• To learn the vesicle-mediated protein trafficking in the early stages and later stages of the secretory pathway

• To understand the receptor-mediated endocytosis

• To know how low-density lipoprotein (LDL) is degraded and its role in hypercholesterolemia

• To learn how ferro ions are transported in mammalian cells

• To understand how membrane proteins and cytosolic materials are directed to lysosome

2. 教学重难点

教学重点:

• The method to study the protein secretory pathway

• Sorting signals directing proteins to specific transport vesicles

• Vesicle-mediated protein trafficking in the early stages and later stages of the secretory pathway

• Receptor-mediated endocytosis and examples

• Degradation of low-density lipoprotein (LDL) and its role in hypercholesterolemia

• Transport of ferro ions in mammalian cells

• Mechanisms for membrane proteins and cytosolic materials directing to lysosome

教学难点:

• Sorting signals directing proteins to specific transport vesicles

• Vesicle-mediated protein trafficking in the early stages and later stages of the secretory pathway

• Degradation of low-density lipoprotein (LDL) and its role in hypercholesterolemia

• Mechanisms for membrane proteins and cytosolic materials directing to lysosome

3. 教学内容

 11-1 Techniques for Studying the Secretory Pathway

 Overview of the Secretory and Endocytic pathways

 Two Basic Requirements for Assays of Intercompartmental Transport

 Pulse-chase Experiments

 Fluorescence Microscopy of Cells Producing a GFP-tagged Membrane Protein

 Assay to Determine Transport of a Membrane Glycoprotein from the ER to the Golgi

 Five Stages in the Secretory Pathway

 A cell-free Assay to Determine Protein Transport from One Golgi Cisterna to Another

11-2 Molecular Mechanisms of Vesicle Budding and Fusion

 Overview of Vesicle Budding and Fusion

 Three Coated Vesicles Involved in Protein Trafficking

 Model for the Role of Sar1 in the Assembly and Disassembly of the COPII Coat

 Sorting Signals That Direct Proteins to Specific Transport Vesicles

 Model for Docking and Fusion of Transport Vesicles with their Target Membranes

 11-3 Early Stages of the Secretory Pathway

 Vesicle-mediated Protein Trafficking between the ER and cis-Golgi -- Forward Transport

 Vesicle-mediated Protein Trafficking between the ER and cis-Golgi -- Reverse Transport

 Three-dimensional Structure of the Ternary Complex Comprising the COPII Coat Proteins Sec23 and Sec24 and Sar1·GTP

 Role of the KDEL Receptor in Retrieval of ER-Resident Luminal Proteins from the Golgi

 Processing of N-linked Oligosaccharide Chains on Glycoproteins within cis-, medial-, and trans-Golgi Cisternae in Vertebrate Cells

 Fluorescence-tagged Fusion Proteins Demonstrate Golgi cisternal Maturation in a Live Yeast Cell

11-4 Later Stages of the Secretory Pathway

 Vesicle-mediated Protein Trafficking from the trans-Golgi Network

 Model for Dynamin-mediated Pinching off of Clathrin-coated Vesicles

 Formation of Mannose 6-Phosphate (M6P) Residues that Target Soluble Enzymes to Lysosomes

 Trafficking of Soluble Lysosomal Enzymes from the trans-Golgi Network and Cell Surface to Lysosomes

 Proteolytic Processing of Proproteins in the Constitutive and Regulated Secretory Pathways

 Sorting of Proteins Destined for the Apical and Basolateral Plasma Membranes of Polarized Cells

11-5 Receptor-Mediated Endocytosis

 Model of Low-density Lipoprotein (LDL)

 Endocytic Pathway for Internalizing LDL

 Model for pH-dependent Binding of LDL Particles by the LDL Receptor

 Familial Hypercholesterolemia (FH)

 Transferrin Cycle Operates in All Growing Mammalian Cells

11-6 Directing Membrane Proteins and Cytosolic Materials to the Lysosome

 Protein ubiquitination and its basic function

 Delivery of Plasma-membrane Proteins to the Lysosome Interior for Degradation

 Model of the Mechanism for Formation of Multivesicular Endosomes

 Mechanism for Budding of HIV from the Plasma Membrane

 The Autophagic Pathway

4. 教学方法

多媒体教学：

• Use illustration and data from literature to demonstrate the experiments to study protein secretion

• Use PPT to show the molecular mechanisms of vesicle budding and fusion

• Use examples to show the early stages and later stages of the secretory pathway

• Use different examples to show the mechanisms for receptor-mediated endocytosis

• Show the mechanism and models for directing membrane proteins and cytosolic materials to the lysosome

互动教学：

• Why was [³⁵S]Met used to study proteins stability, maturation, and degradation in the pulse-chase experiments

• How can we use a cell-free assay to determine protein transport?

• What are by endocytosis and exocytosis?

• What is reverse (retrograde) transport?

• How does the KDEL receptor recruit and release KDEL-containing proteins?

• What is the function of insulin? How is insulin matured?

• What are the possible caused for familial hypercholesterolemia?

5. 教学评价

课后问题：

• What are the Five Stages in the Secretory Pathway? How to Determine Them?

• What are the Requirements for the Study of the Secretory Pathway?

• What are the Three Coated Vesicles Involved in Protein Trafficking?

• How do Transport Vesicles Dock and Fuse with their Target Membranes?

• What are Anterograde and Retrograde Transports?

• What is the Role of the KDEL Receptor in Retrieval of ER Proteins from the Golgi?

• How is Mannose 6-Phosphate (M6P) Formed and What is its Function?

• How are the Soluble Lysosomal Enzymes to Trafficked from the trans-Golgi Network and Cell Surface to Lysosomes?

• How is Proinsulin Proteolytic Processed in the Regulated Secretory Pathways?

• What is the Structure of Low-density Lipoprotein (LDL)?

• Why is pH Important in the LDL Internalization?

• What can Cause Familial Hypercholesterolemia (FH)?

• How is Fe³⁺ Transferred to the Cells?

• What is the Autophagic Pathway?

Chapter 12. Cell signaling（应征）

1. 教学目标 （五号宋体）

• Understand the principle of cell signaling

• Understand the classic cell signaling pathway that contains a G protein, a second messenger, a protein kinase, and several target proteins

• Understand the different types of cell signaling

• Understand the concept and function of signaling receptors

2. 教学重难点

教学重点:

• Cell signaling is everywhere

• The overlap between different cell signaling pathways

• Protein quality control as a cell signaling

教学难点:

• Physicalchemistry properties of signaling regulators

• Phase separation of the kinases and transcriptional regulators

• The polarity and charge of different amino acids

3. 教学内容

12-1 Protein quality control signaling

 Ubiquitin-proteasome system degrades proteins

 Autophagy-lysosome system degrades proteins, organelles and pathogens

 The central role of ubiquitin signal in protein quality control

12-2 External signaling regulates gene expression

 The signal transduction pathway involving a G protein, a second messenger, a protein kinase, and several target proteins.

12-3 Multiple signal transduction pathways coordinate to regulate cell homeostasis

 Signaling pathways that control gene expression and protein degradation

 Crosstalk between signaling pathways and cellular organelles (mitochondria, nucleus and lysosome)

4. 教学方法

多媒体教学：

• Illustration of structure and function of G protein

• Illustration of structure and function of GPCR

• Illustration of kinase and phosphatases

• Illustration of a classic signaling pathway that contains GPCR, G protein, second messenger and protein kinases

• Illustration of protein phase separation

互动教学：

• What is the concentration of a particular kinase or transcriptional regulator in the cell?

• Is there any crosstalk between UPS and autophagy?

• What organelle may contain calcium?

• What can the biological role of the low complexity domain of a protein?

5. 教学评价

课后问题：

• What are the similarities between autophagy-lysosome system and ubiquitin-proteasome system?

• What are the differences between the function of autophagy-lysosome system and ubiquitin-proteasome system?

• Why the signal can be passed from the extracellular region to the cytosol and nucleus?

• Where does the receptor localize in the cell?

• What is the concept of organelle quality control?

Chapter 13. The cytoskeleton（应征）

1. 教学目标 （五号宋体）

• Understand the concept of cytoskeleton

• Understand the structure and basic functions of cytoskeleton systems

• Understand the similarities and differences between actin filament (microfilament) and microtubule dynamics

• Understand the classification and functions of motor proteins

2. 教学重难点

教学重点:

• Treadmilling in actin filament dynamics

• Examples of microfilament-based structures

• Polarity of microtubules

• Actin as the component of microfilament

• Tubulin as the components of microtubule

• The association between molecular motors and cytoskeleton

教学难点:

• Regulation of cytoskeleton function by cell signaling

• Structure of centrosome

• The role of microtubule organizing centers in various biological regulations

3. 教学内容

13-1 Cell Organization and Movement I: Microfilaments

 Overview of the physical properties and functions of the three filament systems in cells

 Cell organization and movement

 Components and dynamics of microfilament

 Structures of microfilament dynamics of actin filaments

13-2 Cell Organization and Movement II: Microtubules

 Structure of tubulin dimers and their organization into microtubules

 Microtubules are assembled from microtubule organizing centers

 Microtubule dynamics and polarity

 Molecular motor proteins: kinesin, dynein and myosin

4. 教学方法

多媒体教学：

• Illustration of actin and microfilament

• Illustration of tubulin and microtubule

• Illustration of intermediate filaments

• Illustration of motor proteins

• Illustration of microtubule organizing center

互动教学：

• If microfilament exists in the nucleus, what could be the potential role?

• What is the relationship between G-actin and F-actin?

• The possible mechanism underlying the nucleation step of microfilament dynamics?

5. 教学评价

课后问题：

• Describe the journey of autophagosomes in cell and neuron?

• What are the functions of the three filament systems in animal cells?

• What are the major components of the above filament systems?

• How does an organelle get its shape?

Chapter 14. Cell cycle（应征）

1. 教学目标 （五号宋体）

• Understand the concept of eukaryotic cell cycle

• Understand the similarities and differences between mitosis and meiosis

• To know what happens in interphase

• Understand the concept of cytoskeleton

• Understand the major steps in mitosis

2. 教学重难点

教学重点:

• Distinct classes of microtubules in mitotic spindle

• Structure of mitotic spindle

• Chromosome capture and congression in prometaphase

• Chromosome movement and spindle pole separation in anaphase

教学难点:

• Regulation of centrosome duplication to the cell cycle

• Condensed chromosome in mitosis

• Meiosis as a special type of cell division

• The role of motor proteins in mitosis

3. 教学内容

14-1 The Eukaryotic Cell Cycle

 Lifespan of different types of cells in the human body

 The stages of mitosis

 Regulation of cell cycle transitions

 Regulation of the cell cycle by the cytoskeleton system

14-2 Mitosis and Meiosis

 The differences between mitosis and meiosis

 The similarities between mitosis and meiosis

 The beauty and complexity mitosis and meiosis

4. 教学方法

多媒体教学：

• Illustration of eukaryotic cell cycle

• Illustration of mitotic spindle

• Illustration of mitosis steps

• Illustration of the similarities and differences between mitosis and meiosis

互动教学：

• How many MTOC(s) does a cell have?

• Are the structure of centrosome changed during mitosis?

• What happens in metaphase?

• What happens in anaphase?

• What happens to the nuclear membrane during mitosis?

5. 教学评价

课后问题：

• What is the function of cyclins and CDKs?

• How many steps does the entire eukaryotic cell cycle have?

• What model organisms can be used to study cell cycle?

• How many stages does meiosis have?

Chapter 15. Integrating cells into tissues（应征）

1. 教学目标 （五号宋体）

• Understand the relationship between cell and tissue

• Understand the major families of cell-adhesion molecules

• Understand the major families of adhesion receptors

• Understand the morphology and function of glial cells and neurons in CNS

2. 教学重难点

教学重点:

• Overview of cell to cell or cell to extracellular matrix adhesion

• Adhesion molecules in cell to cell or cell to extracellular matrix interaction

• Different types of cell junctions

• Relationship between glial cells and neurons

教学难点:

• The similarities and differences between pre- and post-synaptic regions

• Different roles of glial cells in neuronal survival and death

• Classification of extracellular matrix

3. 教学内容

15-1 Cell-Cell/Cell–Extracellular Matrix Adhesion and Junction

 The function of desmosome, tight junction and gap junction

 The structure and components of desmosome, tight junction and gap junction

 Extracellular matrix proteins: proteoglycans, collagens and multi-adhesive matrix proteins

15-2 Cells of Nervous System

 Neuron and glia: the co-players in the nervous system

 The function of astrocyte, microglia and oligodendrocyte

 The contribution of neuronal and glial cells to the disease pathogenesis of neurodegenerative disease

4. 教学方法

多媒体教学：

• Illustration of cell to cell adhesion

• Illustration of cell to extracellular matrix adhesion

• Illustration of extracellular matrix I

• Illustration of extracellular matrix II

• Illustration of the interaction between CNS glial cells and neurons

互动教学：

• Why we say that microglia is a immunological cell？

• Why the cells need to interact with each other?

• What is adhesion molecule?

• What are the key features of anchoring junction, tight junction and GAP junction?

5. 教学评价

课后问题：

• What are the components of the cell-cell and cell-extracellular matrix membrane adhesion?

• What are the differences between the different types of membrane junctions?

• Why the nervous system contains many non-neuronal cells?

• Define the concept of neuroinflammation?

Chapter 16. Cell differentiation and cell death（滕昕辰）

1. 教学目标 （五号宋体）

• Understand the significance of cell differentiation and cell death

• Understand the mechanism of cell differentiation

• Understand the mechanism of programmed cell death

2. 教学重难点

教学重点:

• Definition and mechanism of cell differentiation

• Properties of embryonic stem cells, iPSs and adult stem cells

• Definition of programmed cell death

• Mechanism of apoptosis

教学难点:

• Maintenance of stem cell properties

• Activation of caspases during apoptosis

• Regulation of apoptosis

3. 教学内容

16-1 Cell differentiation during development

 Definition of cell differentiation

 Properties of embryonic stem cells and adult stem cells

 Mechanisms of how a stem cell can maintain its properties

 Mechanisms of cell polarity and asymmetric cell division

16-2 Cell death and its regulation

 Different types of cell death: non-programmed cell death (necrosis), programmed cell death (apoptosis, necroptosis)

 Morphological changes of apoptosis

 General mechanism of apoptosis: intrinsic pathway and extrinsic pathway

 Regulation of apoptosis by Bcl-2 proteins

4. 教学方法

多媒体教学：

• Illustration of cell differentiation during development

• Illustration of stem cell properties

• Illustration of stem cell niches

• Illustration of morphology of apoptosis

• Illustration of extrinsic and intrinsic pathways of apoptosis

互动教学：

• How can one fertilized egg become a multicellular organism?

• What is the possible difference between the stem cell and a differentiated cell?

• What is the consequence if there is no cell death during embryonic development?

• What is a potential drug target in apoptotic pathway for cancer treatment?

5. 教学评价

课后问题：

• What two properties define a stem cell?

• What are the differences between a totipotent stem cell, a pluripotent stem cell, and a precursor (progenitor) cell?

• Why cell death is necessary for maintaining body health.

• Predict the effects of the following mutations on the ability of a cell to undergo apoptosis: a. Mutation in Bad such that it cannot be phosphorylated by protein kinase B (PKB); b. Overexpression of Bcl-2; c. Mutation in Bax such that it cannot form homodimers

四、学时分配（四号黑体）

表2：各章节的具体内容和学时分配表（五号宋体）

五、教学进度（四号黑体）

表3：教学进度表（五号宋体）

六、教材及参考书目（四号黑体）

（电子学术资源、纸质学术资源等，按规范方式列举）（五号宋体）

 1．Molecular Cell Biology，Lodish等编著，第八版，2016年，W. H. Freeman and Company。

 2．Molecular Biology of the Cell，Alberts等编著，第六版，2014年出版，Garland Science。

 3. Molecular Biology: Principles and Practice, Michael Cox等编著, 第二版，2015年出版，W. H. Freeman and Company。

4. Molecular Biology, Robert Weaver, 第五版，2012年出版，McGraw-Hill。

七、教学方法 （四号黑体）

（讲授法、讨论法、案例教学法等，按规范方式列举，并进行简要说明）（五号宋体）

1. 讲授法：用PPT授课，讲授分子细胞生物学中的各个内容，如基因调控，分子运输，信号传导等内容。

2. 讨论法：学生参加教学内容的讨论，提高学生课堂参与度，开阔思维和锻炼表达能力。

八、考核方式及评定方法（四号黑体）

（一）课程考核与课程目标的对应关系 （小四号黑体）

表4：课程考核与课程目标的对应关系表（五号宋体）

（二）评定方法 （小四号黑体）

1．评定方法 （五号宋体）

平时成绩：10%

期中考试：30%

期末考试：60%

2．课程目标的考核占比与达成度分析 （五号宋体）

表5：课程目标的考核占比与达成度分析表（五号宋体）

（三）评分标准 （小四号黑体）