GIST college/Cell Biology/2018-1

Chapter 1

Cells: The Fundamental Units of Life

Prof. Youngsoo Jun

(contact: junys@gist.ac.kr)

School of Life Sciences

Gwangju Institute of Science & Technology
 SYLLABUS
Classification Required Course No. Hrs.:E:Credits 3:0:3 Instructor 송우근 , 송미령 , 전영수
Course Korean 세포생물학
Title English Cell Biology
• Evaluation: 1. 출석 10% 2. 수업참여 , 태도 , Quiz 30% 3. Mid-term exam 30% 4. Final exam 30%,
단 출석율 70% 미만이면 Fail 처리함 .
Course * 필수과목간 중복을 피하기 위하여 , 분자생물학 , 생화학 등에서 다루어지는 내용은 생략하고 ,
Outline 세포생물학 고유 분야 내용을 집중적으로 다룰 예정임 .
* 수업은 매주 월 , 금 2 교시 (10:30 ~ 11:45) 대학 A-112

Textbook Essential Cell Biology, 4th Ed. By Bruce Alberts et al., 2013, Garland Science
Weekly Course Schedule (1~8 weeks)
Date Description *Instructor
03 월 02 일 Course Introduction & Chapter 1. Cells: The Fundamental Units of Life 전영수
3/5, 3/9 Chapter 11. Membrane Structure 전영수
3/12, 3/16 Chapter 11. Membrane Structure 전영수
3/19, 3/23 Chapter 12. Transport Across Cell Membranes; 전영수
3/26, 3/30 Chapter 12. Transport Across Cell Membranes; 전영수
4/2, 4/6 Chapter 15. Intracellular Compartments and Transport 전영수
4/9, 4/13 Chapter 16. Cell Signaling 송미령
Mid-term Exam 송미령
Weekly Course Schedule (9~16 weeks)
Date Description *Instructor
4/23, 4/27 Chapter 16. Cell Signaling 송미령
4/30, 5/4 Chapter 17. Cytoskeleton 송우근
5/11, 5/14 Chapter 17. Cytoskeleton 송우근
5/18, 5/21 Chapter 18. The Cell Division Cycle 송미령
5/25, 5/28 Chapter 18. The Cell Division Cycle 송미령
6/1, 6/4 Chapter 20. Cellular Communities: Tissues, Stem Cells, and Cancer 송미령
6/8 Chapter 20. Cellular Communities: Tissues, Stem Cells, and Cancer 송미령
Final Exam 송미령
Contact 담당교수 : 송미령 (msong@gist.ac.kr) 715-2508 금호연구관 102 호
What is a “Cell” ?

All living things are made of “cells”

=> The fundamental unit of life

 How to define “life”?
1. Highly organized compared to natural inanimate objects
2. Homeostasis, maintaining a relative constant internal environment
3. Living things reproduce themselves
4. Living things grow and develop from simple beginnings
5. Living things take energy and matter from the environment and transform
it
6. Living things respond to stimuli
7. Living things show adaptation to their environment
What is “Cell Biology” about ?

Cell biology :

Modern cell biology = Molecular cell biology

Cytology : descriptive

Pathology
신약개발 과정
 Rodolph Virchow (19th) :

- All diseases are cellular in origin

- Omnis cellula e cellula

(Every cell originates from another existing cell like it)
- Life science: experimental science
- Considerations

Research Interest (Topic)

Research Tool (Model)

Methodology (how?)
 Genetics: why things work?

Genes (genome)

Carbohydrates Nucleic acids

Proteins Lipids

How things work? => mechanism or concept

 Genetics, genomics:

장점 및 한계 :

- 장점 : (1) 논리적 , (2) starting point

- 한계 : How 설명하지 못함 ,
one gene-one protein hypothesis?
one gene-one phenotype hypothesis?

예 : Beta-galactosidase, Lgl (lethal giant larvae)

Gene interaction network
Reductionist approach : Biochemistry

- Cell-free in vitro assay

- Functional reconstitution

Microscopic approach :

- Light microscopy, Fluorescent microscopy

- Electron microscopy
Lgl is a neoplastic tumor suppressor gene in the fruit fly, regulating
epithelial polarity

Larva WT

Eye disc

lgl

WT lgl

WT lgl
Alberts • Bray • Hopkin • Johnson • Lewis • Raff • Roberts • Walter

Essential
Cell Biology
FOURTH EDITION

Chapter 1
Cells: The Fundamental Units of Life

Copyright © Garland Science 2014

 Cells come in a variety of shapes and sizes

Neuron Paramecium Chlamydomonas S. cerevisiae Helicobacter

pylori
Living cells all have a similar basic chemistry
 All living organisms are constructed from cells

A colony of Butterfly Rose Dolphin

bacteria
New cells form by growth and division of existing cells
All present-day cells have apparently evolved from the same
ancestral cell?

neutral

mutations

worse better
Genes provide the instructions for cell form, function, and
complex behavior
Cells form tissues in plants and animals
Some of the internal structure of a living cell can be
seen with a light microscope (>200 nm)
The fine structure of a cell can be seen in a
transmission electron microscope
How big is a cell and its components?
The Prokaryotic Cell
Bacteria come in different shapes and sizes
The bacterium E. coli has served as an important model
organism
Some bacteria are photosynthetic
A sulfur bacterium gets its energy from H2S
The Eukaryotic Cell
Yeasts are simple free-living eukaryotes
The nucleus contains most of the DNA in a
eukaryotic cell
Chromosomes become visible when a cell is about to
divide
Mitochondria can be variable in shape and size
Mitochondria have a distinctive structure
Mitochondria most likely evolved from engulfed bacteria
Chloroplasts in plant cells capture the energy of sunlight
Chloroplasts almost certainly evolved from engulfed
photosynthetic bacteria
Photosynthetic Salamanders: Algae Found in Cells of
Salamander Embryos
Photosynthetic Salamanders: Algae Found in Cells of
Salamander Embryos
The endoplasmic reticulum produces many of the
components of a eukaryotic cell
The endoplasmic reticulum produces many of the
components of a eukaryotic cell
The Golgi apparatus is composed of a stack of flattened
discs
Membrane-enclosed organelles are distributed
throughout the eukaryotic cell cytoplasm
Eukaryotic cells engage in continual endocytosis and
exocytosis
The cytoplasm is stuffed with organelles and a host of
large and small molecules
The cytoskeleton is a network of protein filaments
that crisscrosses the cytoplasm
Microtubules help distribute the chromosomes in a
dividing cell
Where did eukaryotes come from?
Animal cell
Plant cell
Bacterial cell
One protozoan eats another
An assortment of protozoans illustrates the enormous
variety within this class of single-celled microorganisms
Model Organisms
Brewer’s yeast is a simple eukaryotic cell
 The budding yeast
(baker’s yeast),
Saccharomyces
cerevisiae

Figure 1-14 Essential Cell Biology (© Garland Science 2010)

 The fission yeast,
Schizosaccharomyces
pombe

5m
 The budding yeast system provides excellent “genetics”
and “biochemistry”

- Its genome has been completely sequenced

- 6400 genes
- Single gene deletion strain library is available
- Forward genetics : easy mutagenesis & 90 min doubling time,
colony forming
- Easy to purify proteins and organelles in quantity from yeast
cells
Synaptic vesicle fusion mediates neurotransmission
An overview of the synaptic vesicle cycle
BOTOX is a strong inhibitor of synaptic vesicle fusion
A Facile In Vitro Assay Using Engineered Yeast Vacuoles for Membrane
Fusion Driven by Neuronal SNAREs
Problems and limitations in studies for
synaptic vesicle fusion mechanisms

- Mouse genetics: not suitable for mechanism studies

- Primary cells and cell lines (PC-12)
- Synthetic liposomes reconstituted with SNAREs
Reconstitution of the synaptic vesicle fusion
machinery into yeast vacuoles?

Budding yeast (Saccharomyces

cerevisiae)
Reconstitution of the synaptic vesicle fusion
machinery into yeast vacuoles?
Schematic representation of neuronal SNARE-
mediated vacuole fusion assay

(Ko et al., PNAS (2014) 111:7677)

Neuronal SNAREs traffic to the vacuole when
expressed in yeast

(Ko et al., PNAS (2014) 111:7677)

Neuronal SNAREs support vacuole fusion

(Ko et al., PNAS (2014) 111:7677)

Neuronal SNARE-mediated vacuole fusion bypasses
the requirement for Rab and Rab effectors

(Ko et al., PNAS (2014) 111:7677)

SNAP25, the soluble t-SNARE, can be added as
recombinant protein to trigger neuronal SNARE-
driven vacuole fusion

(Ko et al., PNAS (2014) 111:7677)

SNAP25, the soluble t-SNARE, can be added as
recombinant protein to support neuronal
SNARE-driven vacuole fusion

(Ko et al., PNAS (2014) 111:7677)

BoNT/E prevents neuronal SNARE-mediated
vacuole fusion

(Ko et al., PNAS (2014) 111:7677)

 세포노화 ?
 Replicative
aging
 Chronological
aging 분열하는 세포 ( 줄기세포 ,
상피세포 ) 의 노화 : 점차
분열하지 않는 세포 ( 신경세포 분열능력을 상실하고
등 ): 점차 세포 유지 및 궁극적으로 사멸됨
생존능력을 상실하여
궁극적으로 사멸됨
 세포노화의 주요 원인

 활성산소에 의한 산화 스트레스의 축적

 응집성 단백질의 축적

 텔로미어 , 미토콘드리아 퇴화 등
 세포노화의 주요 원인

• 노화인자의 비대칭 분열 및 모세포 축적

노화인자의 비대칭 배분
노화인자 :

응집성 단백질 , 활성산

소,

비정상 세포소기관
( 리소좀 , 미토콘드리아 )

동물세포
세포노화 조절기전의 진화론적 보존
 효모 : 세포노화 연구모델 ?

Bud scar: a measure of replicative aging

Budding yeast ( S.cerevisiae )

탁월한 수명 / 노화 연구 시스템
독성단백질의 비대칭 분열
Arabidopsis thaliana Has Been Chosen Out of 300,000
Species as a Model Flowering Plant

• A small weed (wall cress)

• Produces >1000 off-springs per plant
within 8~10 weeks
• A genome of ~ 110 million nucleotide
pairs, completely sequenced
• Its genes are well conserved in
agricultural species (wheat, rice, etc.)
The World of Animals (metazoa) Is Represented by a Fly, a
Worm, a Fish, a Mouse, and the Human Species
Drosophila melanogaster is a favorite among
developmental biologists and genetics
 The fruit fly Drosophila melanogaster has provided the
foundation of classical genetics

- His studies using the fruit fly provided definitive proof that genes, the
unit of heredity, are carried on chromosomes.
- He won the Nobel Prize in Physiology or Medicine in 1933.

Thomas Hunt Morgan

- He discovered that mutation can be induced by X-rays.

- He won the Nobel Prize in Physiology or Medicine in 1946.

Hermann Joseph Muller

 ~400 eggs/female

8.5 days at 25°C

• a genome of ~ 185 million nucleotide pairs, containing over 13,000 genes,

completely sequenced
 Neoplastic tumor suppressor genes (nTSGs)
nTSGs regulate both epithelial polarity and cell proliferation
: lethal giant larvae (Lgl), Scribble (scrib)

Larva WT

Eye disc

lgl

WT lgl

WT lgl
Caenorhabditis elegans is a small nematode worm
that normally lives in the soil
 Caenorhabditis elegans is the first multicellular organism to have
its complete genome sequenced
• Caenorhabditis elegans : a small nematode worm, an adult is composed of exactly 959
body cells (+ variable number of egg and sperm cells); transparent & colorless; a 97M
bp genome with 19,000 genes

Figure 1-38 Essential Cell Biology (© Garland Science 2010)

Caenorhabditis elegans is the first multicellular organism to have
its complete genome sequenced
• Caenorhabditis elegans : a small nematode worm, an adult is composed of exactly 959
body cells (+ variable number of egg and sperm cells); transparent & colorless; a 97M
bp genome with 19,000 genes

• - Most individuals are “hermaphrodites”

- Generation time: 3~4 days at 22°C, About 3 weeks for life-span
• Its development from the fertilized egg cell to the 959 body cells of the adult has been well
defined.
• Studies of nematode development have led to a detailed molecular understanding of
programmed cell death (apoptosis), a process by which surplus cells are disposed of in all
animals.
• Its development from the
fertilized egg cell to the 959 body
cells of the adult has been well
defined.
• Cell ablation by a laser micro-
beam : killing individual cells or
groups of cells
 C.elegans guys

Sydney Brenner Robert Horvitz John Sulston

These guys shared the Novel Prize in Physiology or Medicine in 2002 for their work on the genetics
of organ development and programmed cell death in C. elegans.
Zebrafish are popular
models for studies of
vertebrate development
 Zebrafish (Danio rerio) are popular models for study of
“vertebrate development”

• Transparent for the first 2 weeks, so ideal to observe how cells behave during early
development in a living vertebrate animal.
• Its genome has been fully sequenced, and its embryonic development is very rapid, and its
embryos are relatively large, robust, and transparent, and able to develop outside their mother.
Furthermore, well-characterized mutant strains are readily available.
• Similar to mammalian models and humans in toxicity testing
The short-lived African turquoise killifish: an emerging
experimental model for ageing
Side-by-side comparison of timing of transgenic line generation using
genetic manipulations in the turquoise killifish, zebrafish and mouse
Cells in culture often display properties that reflect their origin
Biologists also directly study human beings and their cells
Different species share similar genes
The mouse has long been used as the model organism for studying
mammalian genetics, development, immunology, and cell biology

But humans are not mice !

Organisms vary enormously in the size of their genomes