Prof.Dr.

Pratiwi Sudarmono, PhD,SpMK

Andriansjah Rukmana,PhD
Dept.Microbiology,Medical Faculty,University of
Indonesia

Definition
Molecular biology is the study of biology

at a molecular level
The branch of biology that deals with the
formation, structure, and activity of
macromolecules essential to life, such as nucleic
acids, and especially with their role in cell
replication and the transmission of genetic
information (in all living things).
the study of biology from the viewpoint of the
physical and chemical interactions of molecules
involved in life functions.

What is nucleic acid

the organic compounds making up the genetic

material of living cells. Nucleic acids direct the

course of protein synthesis, thereby regulating all
cell activities
Their transmission from one generation to the next is the
basis of heredity.

2 types of nucleic
acid
DNA (deoxyribonucleic acid), which carries the

hereditary information from generation to

generation,
RNA (ribonucleic acid), which delivers the
instructions coded in this information to the
cell's protein manufacturing sites.

1952 : WATSON & CRICK: The coiled structure of a

double-stranded DNA molecule in which strands linked by
hydrogen bonds form a spiral configuration. Also called
DNA helix, Watson-Crick helix.
The genomic era has begun

Life is specified by genomes. Every organism,

including humans, has a genome that contains all of
the biological information needed to build and
maintain a living example of that organism.
The biological information contained in a genome is
encoded in its deoxyribonucleic acid (DNA) and is
divided into discrete units called genes.
Genes code for proteins that attach to the
genome at the appropriate positions and switch on
a series of reactions called gene expression.

Genomic studies in molecular biology

has changed the paradigm in medicine
When Anatomy and Physiology were

discovered : organ approach medicine

Histology and citology plus cytogenetics :
cellular approach
Genomic era : molecular biology approach

Medicine and Medical practices become more sophisticated

DOUBLE HELIX DNA : A-T, C-G

The central dogma

Francis Crick: The Central Dogma is:

"DNA makes RNA, RNA makes protein, and

proteins make us.
But only DNA is inherited to progeny
Inside the cell however DNA must be
transmitted to RNA ( TRANSCRIPTION) to
make protein (TRANSLATION) in ribosom

Genetic variation, evolution

and mutation

A mutation is any change

occurring in the message that a
gene carries. Mutations mainly
arise as copy errors when DNA is
replicated at mitosis and meiosis.

In medicine
Disease occur as a result of host-

parasite/pathogen relationship
Evolution happen in the host genome as
well as in its pathogen
But mutation can happen

spontaneously, or as the impact of

pollution, mutagenic substances in food,
UV light exposure etc.

Sickle cell anemia

Mutation in a globin gene

An influentialstudyhas

identified the key

mutation of the H5N1
influenza virus, needed
for its efficient
replicationin the upper
respiratory tracts of
mice as a mammalian
model.

Indonesia : the highest morbidity and the

highest mortality of Human Avian
Influenzae cases

In the year 2000:the DNA sequence/

genetic map of human has been
completed

President Clinton,
June 26,2000
We are learning the

language in which God created

life......without a doubt, this is
the most important, most
wondrous map ever produced
by humankind
3 billion base pair, until now about 30.000 genes deciphered

After HUGO= human genome

project
Enter the era of functional genomic =

proteomic
With the enormous gene data : scientist
develop new science : BIOINFORMATICS
Last December 2007 : NIH USA launched the

HUMAN MICROBIOME PROJECT

The aim : to understand the genomic function
of human and all microbes reside in the body

Now approach in disease

management has been changed
Based on genome data, as the results of gene

sequencing in healthy as well as sick-patient from

time to time during their disease : we understand
the
MOLECULAR PATHOGENESIS,
ONCOGENESIS,
Molecular basic of human error metabolism
Molecular aspect of inherited diseases
Molecular aspect of cell differentiation and aging
etc.

Based on bioinformatics
The science of PHARMACOGENOMICS is

developed
To understand the relation between human
cell and the medicine/ drugs to produce
better and suitable drug with no side effect

Also based on gene bank data, many

other science and bio-industry are
developed

Forensic medicine
Molecular immunology
Development of vaccine technology using genetic

engineering approach
Gene cloning animal cloning stem cell research
New antibiotics and cytostatic,
Bioterrorism using genetically modified microbes
etc

DEVELOPMENT OF
MOLECULAR
DIAGNOSTICS
As well as EARLY CANCER
DETECTION

GAMBARAN KROMOSOM
PADA Ca mammae

Is your life style directing you to genetic

diversity ?

Bacteria

Genetic material between

prokaryote and eukaryote
No.

Prokaryote

Eukaryote

Location

nucleosome

nucleus

2.

Gene direction

Overlap

One direction

3.

Gene formation

Just exon

Consist exon
and intron

4.

Chromosom

One chromosom

Several
chromosom

Bacterial
Chromosom

Structure bacterial
Chromosomal DNA

Relaxed and supercoiled DNA

Plasmid
Extra chromosomal DNA that replicate

independently of the bacterial chromosome

Size 2.2- 210 kb
Generally carry genes encoding functios that
may be useful to the cell in certain
circumstances
Kinds of plasmid
Fertility (F) plasmid
Resistance (R) plasmid

Hfr (high-frequency recombination) strain

strain that have an F plasmid integrated into

chromosom

F plasmid

R plasmid

F plasmid
transfer

F plasmid
transfer

Hfr strain

Transposon

Resistance character as genetic marker in

DNA recombinant
amp
Plasmid without
resistant gene

Plasmid with
resistant gene

transformatio
n
Bacterial sensitive
ampicilin

Bacterial
sensitive
ampicilin

Bacterial resistant
ampicilin

Bacterial
sensitive
ampicilin

Antimicrobial
Chemotherapy
Mechanism of action of antimicrobial drug
Inhibition of cell wall synthesis
Inhibition of cell membrane function
Inhibition of protein synthesis (ie. Inhibition of

translation and transcription of genetic

material)
Inhibition of nucleic acid synthesis

Origin of drug resistance

1.

2.

Nongenetic origin of drug resistance

Nonmultipying microorganism (metabolically inactive)
Lose the specific target structure for a drug for several
generations
Microorganism infect the host at site where
antimicrobial are excluded or are not active
Genetic origin of drug resistance
Cromosomal resistance
Caused by spontaneous mutation in locus that
controls susceptibility to a given drug
Spontaneous mutation rate 10 -12 to 10-7 (rifampin
resistant occur with high frequency, 10 -7 to 10-5)
Extrachromosomal resistance

Plasmid

The mode action

of -lactamase

The mode action of

resistance to
tetracycline

The mode action of

resistance to
erythromycin

Virus

Genetic in
virus
DNA virus (ss DNA, ds DNA)
RNA virus (ss RNA)

Virus and
its material genetic

Pathway of nucleic acid transcription for

various virus classes
Type of viral
nucleic acid

Intermediates

Type of mRNA Example

+ds DNA

None

+ mRNA

Most DNA virus

(e.g. herpesvirus

+ss DNA

+ds DNA

+ mRNA

Parvovirus

+ds RNA

None

+ mRNA

Reovirus

+ss RNA

+ds RNA

+ mRNA

Picornavirus,
togavirus, flavivirus

-ss RNA

None

+ mRNA

Rhabdovirus,
paramyxovirus

+ss RNA

- DNA, + DNA

+ mRNA

Retrovirus

ds = double-stranded, ss = single-stranded, - indicates negative strand, + indicates

positive strand, + indicates a helix containing a positive and negative strand

Mutation in virus
Genetic drift
Genetic shift

Postulated evolution of human influenza A viruses

from 1889 to 1977

Bacteriophage
Normally called phage, are viruses that infect

bacteria
Can only reproduce inside the cell (obligate
intracellular parasites)
Genome can be DNA or RNA, single stranded
(ss) or double stranded (ds), circular or linear
DNA

Phage genome
Nucleid acid type
DNA

RNA

Structure

Example

Single-stranded

circular

Double stranded

linear
Circular

X174
M13
T phage
PM2

Single-stranded

Linear

MS2

Double-stranded

Linear

Injection DNA to
bacterial host

The life cycle of a typical lytic phage

The life cycle of a typical lysogenic

phage

Genetic transfer
mechanism
Conjugation
Genetic material transfer between

microorganism (bacteria to bacteria)

Transduction
Genetic transfer from virus to bacteria

Transformation
Genetic transfer where naked DNA

were introduced to bacteria

Transformation

Reference
Brooks, G. F., et al., 2004. Jawetz, melnick,
adelberg`s medical microbiology. 23rd ed.
McGraw Hill, Boston
Nicklin, J., et al. 1999. Instant note in
microbiology. Bios Scientific Publishers, Oxford
Salyers, A. A., and Whitt, D. D. 2002. Bacterial
pathogenesis a molecular approach. ASM
Press, Washington
Snustad, D. P., and Simmons, M. J., 2006.
Principles of genetic. 4th ed. John Wiley & Sons