18th October, 2017

Science of Living System

BS20001 (2-0-0)

Dibyendu Samanta
School of Bioscience
Email: dibyendu.samanta@iitkgp.ac.in
Lecture Date Topic
1 19/07/17 Nucleic acids - 1
2 26/07/17 Nucleic acids - 2
3 02/08/17 Transcription and Translation
4 09/08/17 Protein structure - 1
5 16/08/17 Protein structure - 2
6 23/08/17 Enzymes - 1
7 30/08/17 Enzymes - 2

** 06/09/17 CLASS TEST-1 (Enzymes will not be covered)

** 13/09/17 DISCUSSION AND REVISION

8 04/10/17 Photosynthesis and Respiration

9 11/10/17 Cellular architecture

10 18/10/17 Cell division and apoptosis

11 25/10/17 Host defense/Disease biology/vaccines/antibiotics
12 01/11/17 Genetic Engineering & its impact
** 08/11/17 CLASS TEST-2
** 15/11/17 DISCUSSION AND REVISION
Cell Division and Cell Cycle
 What is Cell Division?

Separation of a single cell into two new cells

Very vital event in all living organisms (unicellular or

multicellular)
 What is Cell Division Cycle or Cell Cycle?

Orderly sequence of molecular events in which a single cell

duplicates its contents and divides into two identical cells

This cycle of duplication and division is known as cell cycle

or cell division cycle.
 Molecular Events of Cell Cycle
The detailed molecular events of cell division cycle vary from
organism to organism, and in a single organism it may vary in
time and space
- During early development i.e. embryonic stage, cells divide once in 8
minutes.
- The epithelial cells in the lining of our intestine divide once in 1 day.
- Liver cells divide in 1 year.
- Mostst brain cells (neurons) don’t divide

Most fundamental event in cell division cycle of living

system is common:
Duplication of genetic material/information (DNA) in the parent
cell
Accurate distribution (segregation) of identical DNA into two
cells of next generation (progeny/daughter cells).
 Genetic Material
Chromosome: Specially organized thread-like structure of the
genetic material of an organism involved in storage and
transmission of the biological information (genes) / inheritance of
traits from parents to offspring.

Genome: The complete genetic information (i.e.,

total DNA content) carried by a cell or organism.
DNA is wrapped around Nucleosomes
(histone proteins)
Each Cell Contains Chromosomes, and
Chromosomes Contain Genes
Each Cell Contains Chromosomes, and
Chromosomes Contain Genes

~ 1013
 Chromosome numbers have no apparent
correlation to the organism size
Organism Scientific name
Chromosome 2n = 6
number (2n)
Human Homo sapiens 46

Reeves's Muntjac Muntiacus reevesi 46

Indian Muntjac
Muntiacus muntjac 6
(Barking Deer)

Red ant Formica sanguinea 48

2n=46
Blue whale Balaenoptera musculus 44

Dog Canis familiaris 78

2n=44
2n=1260
Rice Oryza sativa 24

Sugar Cane Saccharum officinarum 80

Adders-tongue Ophioglossum reticulatum 1260

 Concepts of Genome

Most of the higher eukaryotes are diploid (2n) i.e. their body
(somatic) cells contain two copies of the basic genome set
(two sets of homologous chromosomes)

Male Female
 Concepts of Genome
Some eukaryotic cells and the gametes of most higher
eukaryotes are haploid (n) i.e. these cells contain one copy of
the basic genome set (one set of chromosomes)
Somatic Cells (2n) Somatic Cells (2n) Gametes (n)

Mitosis Meiosis 22 + X Egg

(22 x 2) + XX OR
22 + X Egg
2n F

Mitosis Meiosis 22 + X Sperm

(22 x 2) + XY OR
22 + Y Sperm
2n M
 How the ‘2n’ Genome Arises?
Through fertilization of two gametes: one genome set (n)
from male gamete (i.e. sperm) and another genome set (n)
from female gamete (i.e. egg).
n + n ----- 2n

Meiosis 22 + X Egg
OR 2n F
22 + X Egg
2n F

Meiosis 22 + X Sperm
OR
22 + Y Sperm
2n M 2n M
Cell Division
 Important features of Eukaryotic
Cell Division Cycle

 There is a delicate balance between cell growth and division

 Cell division is required to form different tissues and organs
 Key components are: the machinery that carry out cell
division cycle and control system that regulates this
machinery
 The machinery is rebuilt and disassembled every cell division
 Cell division is tightly controlled
Partial or complete loss of normal control on cell division
cycle leads to disease, cancer and death
 Key Steps in Cell Division

Cell growth &

Cell chromosome
division duplication

Repeating pattern of
cell growth (including
chromosome duplication)
and
Chromosome cell division (including
segregation chromosome segregation).
 Steps in Cell Division

Key components of the machinery of cell division cycle:

• Microtubules – One of the three major classes of the filaments of the
cytoskeleton. Tubulins are the monomeric units.
• Kinetochores – Complex structure formed from proteins on a mitotic
chromosome to which microtubules are attached. Helps in the
movement of chromosomes to the poles.
• Centrioles – Short cylindrical array of microtubules.
• Contractile ring – Ring containing actin and myosin that contracts to
pinch the two daughter cells apart.
 Prophase

(microtubule organizing center)

Prometaphase
Metaphase
Anaphase
Telophase
Cytokinesis
 Organelles also need to be segregated
Organelle segregation occurs in three
different ways:
1) Abundant organelles – Organelles
like ribosomes and peroxisomes are
present in large numbers. Hence,
any random distribution will result in
some of these organelles in both
daughter cells.
2) Chloroplast & Mitochondria – They divide by fission like bacterial
cell division, motor proteins move them along microtubules to two
daughter cells.
3) Golgi & Endoplasmic Reticulum – These large organelles divide
into large number of small vesicles. During cell division they get
segregated into the daughter cells. After cell division they fuse
together to reconstitute the intact Golgi and ER.
In Eukaryotic Organism, Two Different types of Cell
Divisions Occur
Mitosis (equal division): When the somatic (body) cells just increase in
number.

One cell --- (genome duplication & segregation into two) ---- Two cells
2n ---(4n)--- 2n + 2n
n ---(2n)--- n + n

Meiosis (reduction division): For sexually reproducing diploid organism

specialized diploid cells (meiocytes) undergo two sequential nuclear
divisions to form four haploid cells.

One cell ---- (genome duplication & segregation into four) ---- Four cells

2n ---(4n)--- (2n) + (2n) ---- n + n+ +n + n

These haploid cells are called gametes (sperms and eggs in plants,
animals) or spores (fungi, algae).
Unique Features of Mitosis and Meiosis Compared

2n 2n Meiosis: single round of

chromosome duplication
4n 4n followed by two rounds of
chromosome segregation.
1st round (Meiosis-I)
segregates the homologs
that pair up.
2nd round (Meiosis-II)
segregates the sister-
chromatids
2n 2n 4n
Mitosis: homologs do not
pair up and segregate
but the sister-chromatids
segregate

n n n n 2n 2n
Unique Features of Mitosis and Meiosis Compared
2n 2n Meiosis: single round of
chromosome duplication
4n 4n followed by two rounds of
chromosome segregation.
1st round (Meiosis-I)
segregates the homologs
that pair up.
2nd round (Meiosis-II)
segregates the sister-
chromatids
2n 2n 4n
Mitosis: homologs do not
pair up and segregate
but the sister-chromatids
segregate

n n n n 2n 2n
Unique Features of Mitosis and Meiosis Compared
Significance of Mitosis and Meiosis
 Cell Division Cycle
(Focusing on Mitosis Division only)
 Essential Events in a Cell Cycle

Cell growth &

Cell chromosome
division duplication

Repeating pattern of
cell growth (including
chromosome duplication)
and
Chromosome cell division (including
segregation chromosome segregation).
 Cell Cycle Alternates Between Mitosis (M) and
Interphase (G1, S, G2)

(Monitor the
environment)
~ 0.5
~ 4.5
hour
hours

~ 10 ~ 9 hours
hours

(Monitor the environment)

A typical human cell has cell division cycle of 24 hours

 Cell Cycle Alternates Between Mitosis (M) and
Phages of cellInterphase
cycle (G1, S, G2)
Interphase – long period of cell cycle
between two divisions. Here cells grow,
2n/ /
2n duplicate chromosomes and prepare for
4n / the division
nn
2n
G1: gap phase – birth of cell to the onset
of chromosome duplication. (the diploid
cells with 2n and haploid cells with n
number of chromosomes)
S: synthesis phase – chromosome
duplication due to replication of DNA
G2: gap phase – end of chromosome duplication (formation of sister
chromatids) to the onset of mitosis. (the diploid cells with 4n and haploid cells
with 2n number of chromosomes)
M: mitosis phase – nuclear division follows division of cytoplasmic content
(cytokinesis) to separate sister chromatids into daughter cells
G0: resting phase – cells exit from cell cycle and survive for days or years
 Some Features of Cell Cycle

A typical human cell has cell division cycle of 24 hours: G1 ~ 9 h,

S ~ 10 h, G2 ~ 4.5 h and M ~ 0.5 h

However, cancer cells and embryonic cells skip G1, and G2, so
cell cycle is shorter

 All normal cells in an individual do not undergo the cell cycle at

the same time (asynchronous)

A few type of cells withdraw from the cycle of division and

remain quiescent (G0 state) for long time or forever (e.g. cells that
are fully differentiated i.e. eye lens cells and nerve cells)
Control of Cell Division Cycle
(Focusing on Mitosis Division only)
Cell Cycle Control System Triggers the
Sequential Events

The eukaryotic cell cycle

control system has three
major checkpoints as
surveillance mechanism for
cell cycle progression or
transitions :
i) Start or restriction point
ii) G2/M checkpoint
iii) Metaphase/anaphase
Cyclins & cyclin-dependent kinases (Cdks): central
components of the cell cycle control system

Central component of cell cycle control

system are cyclin-dependent kinases
(Cdks). Their activities rise and fall as
the cell progresses through its cycle.
This leads to cyclical changes in the
phosphorylation of proteins that initiate
or regulate major cell cycle events.
Cdk activity is primarily controlled by
Cyclin proteins. Cdks are active only
when they tightly bind cyclin.
The levels of cyclin proteins
periodically rise and fall which result in
periodic activation and deactivation of
the Cdks.
 Different classes of cyclins undergo cyclical synthesis and degradation
leading to activation and de-activation of cyclin-Cdk complexes
Cyclin concentration

Cell cycle progression

Three classes of cyclins are required in all eucaryotic cells:
1. G1/S-cyclins bind Cdks at the end of G1 and commit the cell to DNA replication.
2. S-cyclins bind Cdks during S phase and are required for the initiation of DNA replication.
3. M-cyclins promote the events of mitosis.
In most cells, a fourth class of cyclins, the G1-cyclins, helps promote passage through Start
or the restriction point in late G1.
 Some Features of Cell Cycle Control

An interesting theme in the molecular events of cell-cycle control:

In each phase the regulatory molecules activate the steps required
in that particular phase and also prepare the cell for the next phase
of the cell-cycle. Thus, sequential or properly order events/phases
are maintained in the cell cycle.

Partial or complete loss of control of cell-cycle (and apoptosis)

may lead to diseased condition or cancer.

In normal cells, the minor damages in DNA are repaired and
small errors in molecular events are corrected. The cell-cycle
checkpoints delay or arrest the cells to proceed to the next stage
until the DNA damage is repaired or other molecular events of each
phase are completed / corrected before the next step is initiated.
Some features of cell cycle control (contd..)

If the DNA damage can not be repaired or any other faulty
events occurred during any phase of cell cycle, the defective cell
will not complete the division to proliferate, rather the cell death
or apoptosis program will be induced to eliminate them from the
normal healthy organism.

Several defects in the cell cycle checkpoints may lead to

abnormal or faulty molecular events, accumulation of multiple
mutations and DNA rearrangements in the genome resulting in
disease or cancer phenotype.

Understanding the detailed control mechanism of cell cycle will

have significant consequences in the treatment of diseases and
cancer by designing suitable drugs and therapeutic strategies.
Asymmetric Cell Division
Asymmetric cell division is essential to generate
different cell types in multicellular organisms
In multicellular organisms, stem cells can give
SC
NB rise to two different cells, one that resembles the
parent cell and one that does not. Such
Asymmetric division asymmetric cell division generates all different
cell types in the body.
SC IP

In symmetric cell division, the parental cell

gives rise to two daughter cells that resemble
IP each other.
SC
Symmetric division

Daughter cells produced by such asymmetric

SC IP cell division may differ in size, shape, and/or
composition, or their genes may be in different
states of activity or potential activity. The
differences in these internal signals confer
different fates on the two cells.
SC= stem cell
IP= intermediate progenitor
 Important properties of stem cells
1. Pluripotency/multipotency: ability to give rise to any/many cell type of
our body
2. Self-renewal: Ability to reproduce themselves repeatedly
3. Asymmetric cell division: Ability to divide asymmetrically to form one
daughter stem cell identical to itself and one daughter cell that is different
and usually of more restricted potential.
• In this way, mitotic division of stem cells preserves a population of
undifferentiated cells while steadily producing a stream of
differentiating cells.
Current research directions on Stem cells:
 Can be used therapeutically to restore or replace damaged tissue
 For example, if neuronal cells that produce the neurotransmitter dopamine
could be generated from stem cells grown in culture, it might be possible to
treat people with Parkinson’s disease who have lost such neurons.
 Many important questions must be answered before the feasibility of using
stem cells for medicinal purposes.
• The cells of the intestinal epithelium
continuously regenerate from a
stem-cell population located deep in
the intestinal wall in pits called
crypts.
• The stem cells produce precursor
cells that proliferate and differentiate
as they ascend the sides of crypts.
• The time from cell birth in the crypts
to the loss of cells at the tip of the
villi is only about 2 to 3 days.
• The production of new cells is
precisely controlled: too little division
would eliminate villi and lead to
breakdown of the intestinal surface;
too much division would create an
excessively large epithelium and
also might be a step toward cancer.
How asymmetric cell division occurs?
• Essential to asymmetric cell
division is polarization of the
parental cell and then
differential incorporation of
parts of the parental cell into
the two daughters.
• Some cytoplasmic
components (such as mRNA
or proteins) are localized in
some part of the cell.
• The unequal distribution of
these components to the
daughter cells typically result
in transcription of different sets
of genes.
• The resulting proteins
determine the cell-fate.
 Apoptosis
Programmed Cell Death (PCD)

Orderly cellular self destruction

Process: as crucial for survival of multi-cellular

organisms as cell division
 APOPTOSIS

Evolutionarily conserved

Occurs in all multicellular animals (plants too!)

Stages and genes conserved from nematodes (worms)

and flies to mice and humans
STAGES OF CLASSIC APOPTOSIS
Healthy cell

DEATH SIGNAL (extrinsic or intrinsic)

Commitment to die (reversible)

EXECUTION (irreversible)

Dead cell (condensed, crosslinked)

ENGULFMENT (macrophages, neighboring cells)

DEGRADATION
 What are the features of Apoptosis?
Apoptosis is one type of cell death in which a ‘suicidal’ program is
activated within an cell, leading to rapid cell death.

The apoptotic cells shrink, condense, cytoskeleton collapses, and

followed by condensation of nucleus and fragmentation of
chromatin/DNA.

This is an essential and critically important process for organism’s

growth and development, and continues into adulthood or maturity.

In contrast to apoptosis, the animal cells that die accidentally in

response to an acute injury (e.g. trauma or lack of blood supply) or
pathogen infection by a process called cell necrosis.
 Apoptotic Cells are Biochemically Recognizable
Apoptotic cells have characteristics biochemical changes that can be
used to identify the PCD/apoptosis.
1. Chromosomal DNA gets fragmented
2. Phosphatidylserine (a negatively charged phospholipid) which
normally exclusively located in the inner leaflet of lipid bilayer of
plasma membrane, flips to the outer leaflet in apoptotic cells. This
phosphatidylserine, now acts as biochemical marker of the
apoptotic cells.
3. The apoptotic cells lose the characteristic features of normal
mitochondria.
(a) The protein cytochrome C, normally located in the intermembrane
space of mitochondria, released into cytosol in apoptotic cells
(b) Loss of usual electrical potential that exists across of the inner
membrane in normal mitochondria
Necessities or Functions of PCD / Apoptosis
PCD/ Apoptosis eliminates unwanted cells during organ formation /
early development.

Digits formation in mouse paw Removal of tail as tadpole

during embryonic development changes into a frog

Whenever there are damages in cell organelles, these are recognized

very fast and repaired. If the damage is great enough or not repairable,
the cells undergo apoptosis. E.g. DNA damage by various means, if not
immediately repaired, it may lead to cancer-promoting mutation. These
defective cells kill themselves by apoptosis.
 Necessities or Functions of PCD / Apoptosis (Contd..)

PCD/Apoptosis regulates the cell numbers, e.g. in developing

nervous system, number of nerve cells matched/adjusted to the number
of target cells for correct connection/communication.

In adult tissues that are neither growing nor shrinking,

PCD/Apoptosis and cell division must be tightly/correctly regulated to
maintain the exact balance.
 References
• Molecular Cell Biology by Lodish et al

• Molecular biology of The Cell by Alberts et al

Thank You