BB101: Lecture 2

Game of Thrones: Targaryen family tree Game of Thrones: The Iron Throne

Domains, kingdoms and cells

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 If DNA is the hard drive, then what is the computer?
Today we will talk about cells as the smallest unit of life

nucleus

cytoplasm

Schematic of a cell The Central Dogma

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 Topics to be covered in this class

• Definition of life: what is it and why should we bother?

• Domains of life
• Cells as the smallest units of life
• Cell compartments: functionalization
• How do we study cells?
• What are the applications of understanding cell structure?
• Live Demo

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 Topics to be covered in this class

• Definition of life: what is it and why should we bother?

• Domains of life
• Cells as the smallest units of life
• Cell compartments: functionalization
• How do we study cells?
• What are the applications of understanding cell structure?
• Live Demo

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 Biology is the study of life

The phenomenon we call life: defies a simple, one-sentence definition

The condition that distinguishes organisms from inorganic objects

and dead organisms, being manifested by growth through
metabolism, reproduction, and the power of adaptation to
environment through changes originating internally.
-From Dictionary.com

Perhaps, the key words in the definition are “originating internally”.

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 Are we alone in the universe? Can we recognize ‘life’ if we see it?

Why should we define “life” at all?

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 Some basic characteristics of life
Reproduction

Order Growth and development

Response to the Energy processing

environment

Regulation Evolutionary adaptation

AI, Turing test: You have seen movies where robots take over the world. Could robots be ‘alive’?
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 Topics to be covered in this class

• Definition of life: what is it and why should we bother?

• Domains of life
• Cells as the smallest units of life
• Cell compartments: functionalization
• How do we study cells?
• What are the applications of understanding cell structure?
• Live Demo

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 A hallmark of life: diversity

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In order to make sense of the diversity of life: classification into three domains
Bacteria Archaea

Archea
Prokaryotes

2 m
2 m
Eukarya
Kingdom Animalia

Eukaryotes

100 m

Kingdom Plantae

Protists

Kingdom Fungi

We will discuss what these are based on

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 Despite humans making up less
Protists than 1% of the weight of life on
Earth, we have the biggest impact
Archea
Plants on the planet (not always good)
Fungi

Domesticated livestock has

higher biomass than humans!
Bacteria

A brief digression
Diversity and biomass:
Scientists estimate the
giga-tons of carbon from
different kingdoms

From: Vox Science, Animals

based on a paper in
PNAS
 Topics to be covered in this class

• Definition of life: what is it and why should we bother?

• Domains of life
• Cells as the smallest units of life
• Cell compartments: functionalization
• How do we study cells?
• What are the applications of understanding cell structure?
• Live Demo

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 The basic unit underlying the diversity of life: a cell
Cells are not visible to the naked eye and were first discovered when microscopes
were made

What is the size range of cells?

Numbers below show the diameter of a cell from:

Prokaryotes: 0.1 to 5 mm
Archea: 0.1 to 0.2 mm
Eukaryotes: 10 to 100 mm

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 The basic unit underlying the diversity of life: a cell

Organisms can be unicellular or multi-cellular (images below not drawn to scale)

(multi-cellular) (uni-cellular) (uni-cellular) (alive?)

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 Why bother with multi-cellularity? Why not one large cell?

Cross section of a root tip

VERSUS

Human body consisting of organs, tissues and cells

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 Natural laws limit cell size

At a minimum, a cell must contain enough volume to house the

parts it needs to survive and reproduce

The maximum size of a cell is limited by the amount of surface

area needed to obtain nutrients from the environment and
dispose of wastes

Surface area relative to the volume decreases

as the size of a cell increases.
- limits the size of cells

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 There are several ways to improve the SA:V ratio
Multi-cellularity is one such way
Surface area increases while
total volume remains constant Helps in efficient
exchange of heat
5
1 and matter
1

Total surface area

[sum of the surface areas A larger organism
(height  width) of all box 6 150 750
sides  number of boxes] does NOT mean
Total volume
larger cells; just
[height  width  length 1 125 125 more cells; size of
 number of boxes]
the cell remains
Surface-to-volume pretty much the
(S-to-V) ratio
[surface area ÷ volume] 6 1.2 6
same
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 There are several ways to improve the SA:V ratio
Changing the shape of cells is another way
SA:V = 6

SA:V = 3
Can you suggest
another way to improve
the SA:V ratio?
SA:V = 6

SA:V = 16.625

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 Topics to be covered in this class

• Definition of life: what is it and why should we bother?

• Domains of life
• Cells as the smallest units of life
• Cell compartments: functionalization
• How do we study cells?
• What are the applications of understanding cell structure?
• Live Demo

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 Compartmentalization
Compartmentalization: cells can be compartmentalized or not
Floor plan of an affluent home A 1-room tenement
Tenement: a room that by itself is a residence

http://zenlibs.com/a_floorplan-of-a-house/
www.studenthandouts.com/01-Web-Pages/01-Picture-Pages/10.07-
Industrial-Revolution/1-Riis-Family-Living-in-One-Room-New-York-City-
Slum-1890.htm

Specific compartment for each function Easy and cheap to maintain (small)
Privacy and independence of activity Easy to adapt
Easy to pack and move
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Classification of organisms: prokaryotes and eukaryotes (before nucleus and good nucleus)

No nucleus, DNA is a nucleoid

Electron micrograph Electron micrograph

of a section through of a section through
an E. coli cell a yeast cell

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 There are 2 successful cellular plans of organization

Eukaryotes
(true nucleus, that contains DNA)
- cell plan of multi-cellular organisms

Prokaryotes and Archea

(before nucleus, DNA in the form of a nucleoid)
- primitive, simple, versatile, ubiquitous, unicellular life form
- a most successful life form
- 2,500 different species known

See the four types of cells Prokaryote Eukaryote Eukaryote

Eukaryote
Prokaryote or eukaryote? Not nucleated Not nucleated Multi-nucleated Nucleated
Nucleated or not?
Common soil bacteria Monkey heart muscle Amphibian
Human red blood cells esophagus cells
Pseudomonas aeruginosa

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 A typical bacterial cell: carries out all its functions without any compartmentalization

Fimbriae

Nucleoid

Ribosomes

Plasma membrane

Cell wall
Bacterial
Capsule
chromosome
0.5 µm
Flagella
(a) A typical (b) A thin section through
rod-shaped the bacterium Bacillus
bacterium coagulans (TEM)
Structures present only
in some organisms are
labeled in red Figure 6.5

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 What are the compartments in eukaryotic cells? Analogy between a city and a cell
Compartments in eukaryotic cells carry out specialized functions and are called “organelles”.

Golgi (sorting of proteins) (Power stations)

Power stations
cytoplasm
Boundary
(Delhi vs NCR) General Post Office (sorting of mail) Nucleus
(master
controller)
Parliament (master controller)

(Road network) (Boundary)

Map of New Delhi Schematic of a cell

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 Compartmentalization and function: The nucleus contains DNA

DNA is the genetic material

that gives instructions for
cellular function.

In the city analogy, the

nucleus is the government

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 Compartmentalization and function: Mitochondria generate energy

“Mitochondria are the powerhouse

of the cell.”
Based on our city analogy, have you
had power outage in your city?

What would happen if mitochondria

do not function?
Mitochondrial diseases: Leigh
syndrome, MELAS

0.5 -1 m

When any organism ‘eats

food’, mitochondria in the cells
convert the food to energy
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 How do proteins get to the right location in a cell?

The cell has its own Molecular FedEx system:

Endoplasmic Reticulum and Golgi Apparatus

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 Endoplasmic Reticulum transports proteins that are synthesized in the cytosol

Proteins are synthesized

in the cytoplasm and
many proteins carry out
their functions in different
organelles.

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 Golgi Apparatus sorts the proteins for their destinations

Golgi is like a Post Office

Sends proteins: outside the

cell, to different organelles, to
the plasma membrane, etc

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 The cytoskeleton is structural support for the cell and provides tracks for
movement
Cytoskeleton:
Mitochondrion • Actin
• Microtubules
• Intermediate filaments

BUT … as cells can move, the

cytoskeleton is rigid, but can
also be flexible

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 Molecular motors carry cargo on the microtubule tracks
Motor proteins bind to microtubules
and move in a specific direction. ATP
Vesicle
Receptor for
motor protein
One end of the protein can bind to
cellular components and carry them
to their destinations. Motor protein Microtubule
(ATP powered) of cytoskeleton

Microtubule Vesicles 0.25 μm Scanning electron micrograph of

a squid giant axon

Axon: is the extension of a nerve

These are like cell (or neuron)
postmen of the
General Post Shown are two
neurotransmitter-containing
Office in a city vesicles moving towards the tip
of the axon

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 Vesicles moving uni-directionally on microtubules (visualized with a
microscope)

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 Plasma membrane is the barrier between the cell and the world

Plasma
membrane is
made of lipids,
proteins and
carbohydrates

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 The properties of lipids drive compartmentalization and membrane formation
Charged phosphate groups

Phospholipids have hydrophilic heads

(water loving) due to the negatively
charged phosphate groups.
They have hydrophobic tails (water
hating) that have no charged groups.

Because of this structure phospholipids

spontaneously assemble into structures
that form membranes.

Cholesterol and proteins embed in the

Hydrophobic tails
lipid membranes: fluid mosaic model
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 The properties of lipids allow spontaneous formation of ordered structures

• Can put drugs and other useful

molecules into this aqueous
compartment for delivery

• Can fuse membranes together

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 The properties of lipids lead to membrane fusion

Pfizer/Moderna Covid-19 vaccine

Vaccinate

Membranes do not easily fuse with each other:

Liposomes and Lipid Nanoparticles (LNPs) have certain

lipids that promote fusion

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 Where did organelles come from?

Prokaryotes were engulfed by eukaryotes

to create endosymbiotic organelles

Evidence for this hypothesis?

Organelles have small genomes
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 Animal vs plant cells: structure is essential for function

(Use carbon dioxide and

water to make “food”)
(Help maintain water
balance)
(Rigidity)

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 Classification of organisms: viruses (completely different)

Small viruses
Giant viruses

This is one of the smaller viruses

Sizes of viruses vary greatly
Some viruses are larger than bacteria

https://en.wikipedia.org/wiki/Giant_virus

SARS-CoV2
Viruses cannot survive without a host cell to infect: are they even alive?
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Viruses cannot survive without host cells: all machinery to make new viruses is in host cells

1) Attach to our cells

SARS-CoV2

4) Use the Golgi to send the

new viruses outside the cell
2) Uncoat the RNA genome
and cell makes viral proteins

3) Cell transports proteins in the ER

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 Topics to be covered in this class

• Definition of life: what is it and why should we bother?

• Domains of life
• Cells as the smallest units of life
• Cell compartments: functionalization
• How do we study cells?
• What are the applications of understanding cell structure?
• Live Demo

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 How do biologists study cells?

Reducing the complexity of a system

Break down the system into component parts, or simplify it
to understand how it works
Reductionist approach: reduce the complexity of a system
to understand how it works

(stardust.jpl.nasa.gov)

A rocket is a complex man-made system

Many parts, assembly instructions

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 How do biologists study cells?

Towards getting a component list for cells….

Our quest for the “assembly manual” starts from a study of cells
Two questions to answer upfront:
• There are so many types of organisms, how to study all of them?
Or, is it necessary to study all of them?
It suffices to study few model systems which are easy to work with
in the laboratory (short generation time, ease of growing, etc.)
• Most cells are small in size and hence are not visible to naked eye.
How to study objects that are cannot be seen?
Cell fractionation studies, microscopy

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 Choice of experimental system

Molecular logic of life is highly conserved

5 µm

Cross section
of a cilium

15 µm

Cilia of Cilia of
Paramecium windpipe cells

0.1 µm

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 Due to common principles of life, biologists study model systems
Some model systems that represent different kingdoms, also Mus musculus (mouse; for mammals)

Escherichia coli Zebra fish (Danio rerio) Caenorhabditis elegans

www.cdc.gov wikipedia A free living round worm
wikipedia Arabidopsis thaliana
Some strains inhabit our gut Tropical fresh water fish
Some strains are pathogenic A weed (www.esa.int)

Saccharomyces cerevisiae
Baker’s yeast, wikipedia
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Neurospora crassa
Drosophila melanogaster Xenopus laevis
Bread mold (fungus)
Fruit fly, wikipedia African clawed frog, wikipedia
www.devbio.biology.
gatech.edu
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 How many cells in an organism?

C. elegans: a model organism

• A worm, <1 mm long

• Feeds on bacteria, etc., found in decaying organic matter
• Being studied for the last 50+ years - developmental biology and
neurobiology
• Transparent body allows inspection of internal workings in live worms
https://en.wikipedia.org/wiki/Caenorhabditis_elegans
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 How many cells in C. elegans?

• Adult male has

exactly 1031 cells!

• Lineage of each and

every cell is known

• Growth is by
enlargement of cells,
not by division

http://www.wormbook.org/chapters/www_specnervsys.2/neurogenesis_fig2.jpg
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 C. elegans is a model for human development

How many cells in a human? Approximately 10 12

Neurons (nerve cells)

• Long projections called
Erythrocytes (red blood cells) axons to send electrical
• Biconcave, no nucleus and signals to other cells
flexible to squeeze through
blood vessels
• Carry oxygen due to
haemoglobin, making them
red in color

Shape and structure leads to function

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 How to break up cells into component parts?

Take your favorite cells

Break cells by physical shearing, chemical

lysis, etc.

Centrifugation: subject cell lysate to

centrifugal forces that separate
components based on density/size.

Biochemical methods: determine the

functions of each component

Microscopy: visualize the components in

each fraction

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 Microscopes are essential for viewing cells (breakthrough technology of the 1600s)

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 The outcome of a reductionist approach

Sub-cellular structures that we have been discussing in this class

Baker’s yeast

Bacteria versus yeast:

Size
Compartments within the cell
(sub-cellular organelles)
A typical bacterium Function-based specialization

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 Topics to be covered in this class

• Definition of life: what is it and why should we bother?

• Domains of life
• Cells as the smallest units of life
• Cell compartments: functionalization
• How do we study cells?
• What are the applications of understanding cell structure?
• Live Demo

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 Knowledge of cells is useful in medicine
Uterine cervix cells
• Pap smear test is a non-invasive procedure used for early
detection of cancer and viral infections
• Routine test… followed up by other sensitive tests, if
warranted
Normal • Cells from an affected individual are larger in size and may be
multi-nucleated
• Image analysis is being tested to make this more accurate and
efficient (Tata Centre for Technology Development)

• Happiness & well-being (individual)

• Lower healthcare burden (economy)
Infected with papilloma virus https://cnx.org/contents/GFy_h8cu@11.2:ADrtuvNU@8/Studying-Cells

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 Knowledge of cells is useful in medicine

• Diagnosis of malaria is by visualizing blood cells

stained with a dye that turns DNA purple
• Microscopy is done in the hospital to detect malaria
parasites in red blood cells so that treatment with
anti-malarial drugs can start
• Image analysis is being tested to make the process
more efficient and reliable (many labs @IITB)

• Happiness & well-being (individual)

• Lower healthcare burden (economy)
https://www.cdc.gov/malaria/diagnosis_treatment/diagnostic_tools.html

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 Topics to be covered in this class

• Definition of life: what is it and why should we bother?

• Domains of life
• Cells as the smallest units of life
• Cell compartments: functionalization
• How do we study cells?
• What are the applications of understanding cell structure?
• Live Demo

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 In-class demonstration of a microscope based on your cell phone

Prof. Debjani Paul’s lab in the BSBE department has devised a cell phone microscope
that is now spun off into a start-up company

Savita Kumari, PhD student at IIT-Bombay | Microfluidics Research

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