28/03/2014 MODIFIED by Prof.

Sismindari 1
farmasibugm2012@gmail.com
Kuliah ke
Dosen
Pokok Bahasan Sub Pokok Bahasan
I.Prof.
Sismindari

1)
Pengenalan
Biologi
molekuler
Peranan Biologi Molekuler dalam Farmasi, - - Contoh perkembangan
dalam Biologi Molekular : kloning domba Dolly dan terapi sel induk
materi genetik : Genom, kromosom, gena, DNA, RNA,
protein.Perbedaan genom prokariot dan mamalia, lokasicentromer,
telomere, dan origin replikasi, human genom project- Dogma sentral
ekspresi gen:replikasi, transkripsi, translasi-
II. 2) + 3)
Dr. Puji A.
Organisasi dari sel
Struktur dan fungsi organela sel
Arsitektur sel: Cytoskeleton & Cell Junction
materi genetik : Genom, kromosom, gena, DNA, RNA, protein.
Struktur DNA (model Watson dan Crick) dan RNA, base-pairing DNA,
Sifat DNA dan RNA
Heterochromatin, Karyotyping Chromosome
Pertumbuhan,
Perkembangan dan
Diferensiasi Sel
- Penurunan sifat materi genetic, Pertumbuhan Sel
Pembelahan Sel, meiosis dan mitosis (metaphase, anaphase, interfase)
Hukum Mendel
Diferensiasi Sel, Komunikasi Antar Sel
III.4) +5)
Prof
Sismindari
Replikasi DNA
(Sintesis DNA)
-Reaksi polimerisasi, Proses replikasi DNA: konservatif dan semi-
konservatif, inisiasi, elongasi replikasi, - Garpu replikasi, fragmen
Okazaki, peran telomere, peran enzim topoisomerase, mekanisme
proofreading, mutasi karena triple repeat.
-- Obat yang bekerja pada tahap replikasi: penghambat topoisomerase,
basa analoh sebagai obat antivirus
- Penggunaan PCR
28/03/2014 MODIFIED by Prof. Sismindari 2
Kuliah ke
Dosen
Pokok Bahasan Sub Pokok Bahasan
III. 5)
Prof
Sismindari

Mutasi dan
Repair DNA
- Definisi, mutan, mutasi, mutagen; jenis-jenis mutasi, jenis-jenis
mutan, jenis-jenis mutagen (kimia, fisika dan biologi), mutasi pada
level gen, pada level organisme. - Stabilitas genetik dan kerusakan
DNA, macamkerusakan DNA, proses umum reparasi DNA, penyakit
yang disebabkan oleh adanya mutasi
III.6)
Prof Djadi
Polimorfism
SNP kaitannya dengan keragaman genetik masing-masing
individu: Farmakogenomik aplikasinya pada metabolisme INH dan
warfarin
Polimorfisme mikrosatelit :Sidik jari DNA aplikasinya pada
hubungan kekerabatan dan identifikasi individu dengan PCR
Hibridisasi, macam dan prinsip kerjanya (Southern, Northen)

7) Mekanisme infeksi virus
dan Transformasi
genetik
- Macam-macam virus (virus DNA, virus RNA), genom virus,
Life cycle HIV, Virus influenza, EBV, dan retrovirus
Jenis transposon: transposon, viral retrotransposon dan non-viral
retrotransposon.
- Mekanisme transposisi
Penyakit yang disebablkan oleh transposon


28/03/2014 MODIFIED by Prof. Sismindari 3
Dosen Pokok
Bahasan
Sub Pokok Bahasan
IV. Prof
Kuswandi
8)
Ekspresi Gen:
Transkripsi,
prokariot,
eukariot
Transkripsi pada prokariot :
RNA polimerase: inisiasi (TATA Box, promoter), elongasi,
terminasi.
Fenomena transkripsi pada prokariot : polisistronik, polisom,
repressor, aktivator dan induser
Fenomena transkripsi eukariot: intron, ekson, capping, splicing
dan poli-A, monosistronik
Obat-obat yang bekerja pada penghambatan proses transkripsi

Regulasi: Sistem operon, Lac repressor dan Catabolic activator
protein (CAP), triptofan operon
9) Ekspresi Gen:
Translasi
Ribosom, kodon antikodon , tRNA, aminoasyl tRNA sintetase
Proses : inisiasi, elongasi, dan terminasi
Perbedaan proses translasi pada prokariot dan eukariot.
Pasca translasi : modifikasi asam amino.
Obat-obat dengan target penghambatan proses translasi
prokariot (antibiotik).
Teknik deteksi ekspresi gen
V. Dr Riris
10)
Sistem regulasi
ekspresi gen
eukariot
factor transkripsi, domain dan motif, contoh factor transkripsi,
dan peran factor transkripsi.
Signal transduksi sederhana (hormone steroid),
Signal transduksi kompleks (jalur MAP-K dan ras protein)
28/03/2014 MODIFIED by Prof. Sismindari 4
Dosen Pokok
Bahasan
Sub Pokok Bahasan
11) Dr. Riris
Sistem regulasi
melalui second
messenger
G-protein signaling : G-protein, jalur cAMP, jalur protein kinase C
(PKC)
Aplikasi regulasi pengendalian ekspresi gen pada proses
pengobatan

12) Prof.Edy M


Cell-cycle dan
regulasinya
Overview : tahapan pembelahan sel dan daur sel (G1-S-G2-M-
phases),
Kontrol daur sel pada G1-phase (peran cyclin-cdk dan pRb),
pengaturan sistem checkpoint pada daur sel
Apoptosis (kematian sel terprogram) : jenis kematian sel,
karakteristik morfologi apoptosis, jalur instrinsik dan ekstrinsik,
peran pro dan anti apoptosis (bcl2 famili)
Peran mitokondria.
Teknik deteksi apoptosis

VII. 13) 14)
Karsinogene
sis
Pengertian dasar kanker, tahap-tahap karsinogenesis, golongan
agen karsinogenik (kimia, fisika, dan biologi), pengenalan marker
molecular kanker (mis. Ras dan p53) dan perannya pada proses
karsinogenesis, pengembangan agen kemoprevensi
28/03/2014
MODIFIED by Prof. Sismindari 5
28/03/2014 MODIFIED by Prof. Sismindari 6
III. DAFTAR PUSTAKA

Lodish, H., Berk, A., Zipursky, A.L., Matsudaira, P., Baltimore, D., Darnell, J., 2000,
Molecular cell Biology, 4th ed., Freeman and Company, New York.

Alberts,B., Bray, D., Lewis, J., Raff, M., Robert, K., Watson, JD., 1994, Molecular
Biology of the Cell, 3th ed.,Garland Publishing, Inc, New York.

Devlin T.M., 2002, Biochemistry with Clinical Correlations, 5th ed., wiley-Liss,
New York.

Berg, J.M., Tymoczko, J.L., Stryer.,2002, Biochemistry, 5th ed.,W.H. Freeman
and Company, New York.

Glick, B.R. and Pasternak, J.J., 1998, Molecular Biotechnology, Principles and
Applications of Recombinant DNA, 2nd. Ed. ASM Press, Washington DC.

Sismindari, 2012, Seri Biologi Molekuler: Replikasi DNA, Pustaka Pelajar,
Yogyakarta

28/03/2014 MODIFIED by Prof. Sismindari 7
Peranan Biologi Molekuler dalam Farmasi.
Materi genetik : Genom, kromosom, gena,
DNA, RNA, protein.
Perbedaan genom prokariot dan mamalia,
lokasi centromer, telomere, dan origin
replikasi, human genom project
Dogma sentral ekspresi gen : replikasi,
transkripsi, translasi
Contoh perkembangan dalam Biologi
Molekular : kloning domba Dolly dan terapi sel
induk
28/03/2014 MODIFIED by Prof. Sismindari 8
How to do well in Mol Biol
Study every day
Dont just look at notes, rewrite, reorganize,
redraw pictures from memory
When read book, take notes
Ask questions
Come to office by appointment
28/03/2014 MODIFIED by Prof. Sismindari 9
28/03/2014 MODIFIED by Prof. Sismindari 10
46
(Berg JM et al, 2002)
Human 2.9x10
9
bp
Molecular Biology
The field overlaps with other areas of biology, particularly genetics and
biochemistry
Molecular biology concerns itself with understanding the interactions
between the various systems of a cell, including the interrelationship of
DNA, RNA and protein synthesis and learning how these interactions
are regulated.
28/03/2014
MODIFIED by Prof. Sismindari
11
Schematic relationship between biochemistry, genetics and molecular biology
Function
Genes Proteins
Biochemistry
Molecular Biology
Genetics
introduction%20to%20molecular%20and%20cell%20biology.ppt
28/03/2014 MODIFIED by Prof. Sismindari 12
28/03/2014 MODIFIED by Prof. Sismindari 13
Mengapa
mempelajari
MANFAAT BIOLOGI MOLEKULER
28/03/2014 MODIFIED by Prof. Sismindari
14
GENOME
MUTASI DNA
PADA GENOME
REPLIKASI DNA
TRANSKRIPSI
TRANSLASI
1. SIFAT & FUNGSI
BERUBAH
2. SIFAT & FUNGSI
TETAP
TERJADINYA PENYAKIT
PERUBAHAN RESPON
OBAT
PROTEIN, RESEPTOR
TARGET OBAT
PROTEIN OBAT
TARGET TERAPI
PCR
SEKUENSING
MANFAAT BIOLOGI MOLEKULER
28/03/2014 MODIFIED by Prof. Sismindari
15
REGULASI
PROKARIOT
REGULASI
EUKARIOT
REGULASI
SIKLUS SEL
BAGAIMANA SIGNAL DARI LUAR
DITERUSKAN KE DLM SEL
SIGNAL DI DITERUSKAN MELALUI
RESEPTOR
BAGAIMANA PEMBELAHAN SEL
NORMAL DIATUR AGAR TDK TERJADI
KANKER
REGULASI
SECOND
MESSENGER
- RESPON BAKTERI THDP LINGKUNGAN
- MEMPRODUKSI PROT OBT DLM BAKTERI
- RESPON HUMAN THDP LINGKUNGAN
- PROSES METABOLISME
- SAAT TERJADI INFEKSI PATOGEN
28/03/2014 MODIFIED by Prof. Sismindari 16
KETERKAITAN DENGAN ILMU LAIN
What is Life made of:
All living things are made of Cells
Nucleus = library
Kromosom = bookshelves
Genes = books
Almost every cell in an organism contains
the same libraries and the same sets of
books.
Books represent all the information (DNA)
that every cell in the body needs can
grow and carry out its various functions.

All Life depends on 3 critical molecules From
DNA, to RNA, to Proteins



28/03/2014 MODIFIED by Prof. Sismindari 17
Nucleus
DEVIDED & PASSED
THE GENETIC INFORMATION
in to the doughter cells
28/03/2014 MODIFIED by Prof. Sismindari 18
PERBEDAAN PROKARIOT & EUKARIOT
28/03/2014 MODIFIED by Prof. Sismindari 19
Prokariot Eukariot
Organisme Bakteria dan sianobakteria Fungi, hewan, manusia
Ukuran sel 1 - 10m 5 - 100m
Organel Beberapa / tidak ada Inti, mitokondria, kloroplast
GENOM Sirkuler dalam sitoplasma,
Satu molekul kromosom
Linier panjang, dipak rapi dgn
protein histon dalam inti.
Manusia mempunyai 46
cromosom
RNA dan
protein
Disintesis dalam
sitoplasma
RNA : dalam inti, Protein: dalam
sitoplasma
Organisasi Unisel Multisel
PERBEDAAN PROKARIOT & EUKARIOT
(Alberts B, et al, 1994)
Splising
Eukariot
Prokariot
28/03/2014 MODIFIED by Prof. Sismindari 20
28/03/2014 MODIFIED by Prof. Sismindari 21
DNA, RNA, and the Flow of Information
28/03/2014 MODIFIED by Prof. Sismindari 22
Translation Transcription
Replication
Functional
Proteins
Post translation
modification
28/03/2014 MODIFIED by Prof. Sismindari 23
PEMBELAHAN
SEL
28/03/2014 MODIFIED by Prof. Sismindari 24
28/03/2014 MODIFIED by Prof. Sismindari 25
FENOTIP
28/03/2014 MODIFIED by Prof. Sismindari 26
Kromosom
tanpa histon
DNA CHROMOSOME
28/03/2014 MODIFIED by Prof. Sismindari 27
KROMOSOM
CENTROMER
region dari chromosom yang diperlukan untuk
pengikatan mitotic spindle saat proses mitosis
TELOMER
fragmen di ujung chromosom linier
replikasi secara khusus
untuk mencegah perpendekan chromosom
ORIGIN REPLIKASI
tempat awal replikasi berlangsung
Telomere Length Declines
28/03/2014 MODIFIED by Prof. Sismindari 28
0 35
65
1,500
3,000
8,000
Age (years)
Telomere length
in base pairs
(human white
blood cells)
Chromosomes
28/03/2014 MODIFIED by Prof. Sismindari 29
16
6
24
78
40
46
28/03/2014 MODIFIED by Prof. Sismindari 30
E. Coli 4.7 x 10
6
1 Chromosom
40 50 loop superkoil
Human 4 x 10
9
22 autosom yang berbeda
2 sex kromosom
Masing2 single linier DNA

diploid 2 copies ech chromosome
2 copies each gene
1 X chrom in male

28/03/2014 MODIFIED by Prof. Sismindari 31
Aplikasi biomol 1
28/03/2014 MODIFIED by Prof. Sismindari 32
You can tell people apart by their
fingerprints
28/03/2014 MODIFIED by Prof. Sismindari 33
Because everyones fingerprints are different!
DNA is like a fingerprint because
everyones is a little different!
MODIFIED by Prof. Sismindari
34
How does the police look at DNA to
figure out who committed a crime?
28/03/2014




Miss Ellis Sara
This is what it really looks like!!! 28/03/2014 MODIFIED by Prof. Sismindari 35
28/03/2014 MODIFIED by Prof. Sismindari 36
28/03/2014 MODIFIED by Prof. Sismindari 37
Anticipated Benefits:
improved diagnosis of disease
earlier detection of genetic predispositions to disease
rational drug design
gene therapy and control systems for drugs
personalized, custom drugs
Medicine and the New
Genetics
28/03/2014 MODIFIED by Prof. Sismindari 38
U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003
Gene Testing Pharmacogenomics Gene Therapy
Aplikasi 2
POLIMORFISME
28/03/2014 MODIFIED by Prof. Sismindari 39
Why does drug response vary?
28/03/2014 40 MODIFIED by Prof. Sismindari
Same symptoms,
Same findings,
Same disease? Same drug
Same dose
Different Effects
Different patients
Possible Reasons:
Individual variation
By chance
Ethnicity
Age
Weight
Pregnancy
Genetic factors
Disease
Drug interactions..
Genetic
Differences
A
G
SNP
Pharmacogenomics
Single Nucleotide Polymorphisms (SNPs)
A key to human variability
28/03/2014 MODIFIED by Prof. Sismindari 41
DNA sequence variation at a single nucleotide that may
alter the function of the encoded protein
Functional but altered protein
Functional protein
Polymorphisms are common and contribute to common diseases and
influence our response to medications
*
Phase II enzymes known to have
polymorphism
28/03/2014
MODIFIED by Prof. Sismindari
42
NAT2(N-acethyl Transferase): Isoniazid, hydralazine,
GST: D-Penicillamine
TPMT: Azathioprine, 6-MP
Pseudocholinesterase: Succinyl choline
UGT1A1: Irinotecan
"Here's my
sequence..."
The New Yorker
28/03/2014 MODIFIED by Prof. Sismindari 43
APLIKASI BIOMOL UNTUK KLONING
28/03/2014 MODIFIED by Prof. Sismindari 44
The Making of Dolly
28/03/2014 MODIFIED by Prof. Sismindari 45
Cloning depends on DNA
Step 1: Take the Nuclei out of a sheep egg
Empty
DNA
DNA
Step 2: Transfer nuclei from the Mother
Sheep Egg
Mothers Egg
Hello Dolly
She was cloned using a cell taken from a healthy
six-year-old sheep
28/03/2014 MODIFIED by Prof. Sismindari 46
July 5, 1996, Dolly was born at the
Roslin Institute, Edinburgh, Scotland
Good-Bye Dolly
Dollys DNA was already 6 years old when she
was born - WHY?
28/03/2014 MODIFIED by Prof. Sismindari 47
At age 3 Dolly showed signs of premature
aging.
Dolly died at 6 years old from progressive
lung disease (symptom of old age)
Its all about DNA
Other Cloned Animals
28/03/2014 MODIFIED by Prof. Sismindari 48
July 1998
cloned calves
Cloned
mule
Cloned
mouse

28/03/2014 MODIFIED by Prof. Sismindari 49
28/03/2014 MODIFIED by Prof. Sismindari 50
KOMPOSISI GENA
FUNGSIONAL
PROMOTER
OPERATOR
ACTIVATOR BINDING SITE
STRUKTURAL GEN : mRNA
TERMINATOR
Introduction
The Central Dogma
of Molecular Biology
28/03/2014 MODIFIED by Prof. Sismindari 51
mRNA
Transcription
Cell
Polypeptide
(protein)
Translation
Ribosome
Reverse
tanscription
DNA
28/03/2014 MODIFIED by Prof. Sismindari 52
28/03/2014 MODIFIED by Prof. Sismindari 53
28/03/2014 MODIFIED by Prof. Sismindari 54

28/03/2014 MODIFIED by Prof. Sismindari 55
56
ASISITENSI
ASISTEN BIOLOGI SEL &
MOLEKULER
28 Februari 2014
28/03/2014 MODIFIED by Prof. Sismindari
TATA TERTIB LABORATORIUM

Mahasiswa Datang 15 menit sebelum praktikum dimulai
Jas laboratorium dan name tag dipakai sebelum memasuki laboratorium
Mahasiswa tidak diperkenankan pakai SANDAL dan KAOS OBLONG
Mahasiswa terlambat 15 menit tanpa alasan yang jelas tidak
diperkenankan mengikuti praktikum
Mahasiswa diwajibkan untuk MENGIKUTI SEMUA MATA PRAKTIKUM
Tidak disediakan waktu khusus untuk inhal.
Mahasiswa yang berhalangan hadir bisa mengikuti PRAKTIKUM
GOLONGAN LAIN untuk acara yang sama
Mahasiswa tidak diperkenankan MAKAN, MINUM, MEROKOK selama
praktikum
Laporan praktikum dibuat BER-KELOMPOK dan dikumpulkan saat
mengikuti praktikum berikutnya


28/03/2014 MODIFIED by Prof. Sismindari 57
58
Percobaan
Percobaan 1 : Isolasi DNA MAMALIA
Percobaan 2A : KUANTIFIKASI DNA HASIL ISOLASI
DENGAN SPEKTROFOTOMETRI
Percobaan 2B : AMPLIFIKASI DNA HUMAN DENGAN
PCR UNTUK MELIHAT POLIMORFISME
Percobaan 3 : ANALISIS DNA DGN ELEKTROFORESIS
GEL AGAROSE
Percobaan 4: PENGAMATAN SEL DENGAN MIKROSKOP
Percobaan 5: PENGENALAN BIOINFORMATIKA BLAST
Percobaan 6: SIMULASI DETEKSI EKSPRESI PROTEIN
DENGAN TEKNIK WESTERN BLOT
28/03/2014 MODIFIED by Prof. Sismindari
59
Penilaian
Test : 30
Kerja : 10
Laporan : 20
Responsi : 40

NILAI UJIAN (UTS+UAS)
NILAI AKHIR
{(3XNILAI UJIAN)+NILAI PRAKTIKUM}/4
BOBOT 1
BOBOT 3
28/03/2014 MODIFIED by Prof. Sismindari
SISTEM EVALUASI
NILAI AKHIR
A > 75
B 65 74
C 55 64
D 35 54
E <34


28/03/2014 MODIFIED by Prof. Sismindari 60