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7/27/2019 Introduction to Molecular and Cell Biology
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Ulf Schmitz, Introduction to molecular and cell biology 1
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BioinformaticsBioinformaticsIntroduction to molecular and cell biologyIntroduction to molecular and cell biology
Bioinformatics and Systems Biology Groupwww.sbi.informatik.uni-rostock.de
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Outline
1. Recommended Literature
2. What is Bioinformatics?3. The Cell
4. Molecular Biology / Genomics
1. Genes
2. DNA
3. RNA4. Proteins
5. Gene Expression
5. Signaling Pathways
6. Outlook next lecture
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Recommended Literature
Developing Bioinformatics Computer Skil ls; CynthiaGibas & Per Jambeck; OReilly; ISBN: 1565926641
New Biology for Engineers and Computer Scientists;Aydin Tzeren & Stephen W.Byers; Pearson Prentince HallBioengineering; ISBN: 0130664634
Bioinformatics: Sequence and Genome Analysis; DavidW. Mount; Cold Spring Harbor; ISBN: 0879697121
Introduction To Bioinformatics; Arthur M. Lesk; OxfordUniversity Press ISBN: 0199277877
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What is Bioinformatics?
Bioinformatics: is the development and use of computer
applications for theAnalysis, Interpretation, Simulation andPrediction of biological Systems and corresponding
experimental methods in nature sciences.
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Chemistry
Mathematics
Statistics
Computer Science
Informatics
Physics
Medicine
Biology
Molecular Biology
Bioinformatics
What is Bioinformatics?
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History of Bioinformatics
Biologists were searching for algorithms to analyze andinterpret their huge amount of empiric biological data
As well as computer aided modeling and simulation
International molecular biological databases arose to
make data internationally accessible and comparable
Algorithms for gene- and protein prediction wheredeveloped
These efforts lead to the development of artificialneuronal networks, genetic algorithms and evolutionstrategies
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Bioinformatics
Offers an ever more essential input to
Molecular Biology Pharmacology (drug design)
Agriculture
Biotechnology Clinical medicine
Anthropology
Forensic science
Chemical industries (detergent industries, etc.)
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Organism, Organ, Cell
Organism
Organ
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The ER modifies proteins, makes macromolecules,
and transfers substances throughout the cell.
Ribosome translates
mRNA into a polypeptidechain (e.g., a protein).
Mitochondrion
manufactures adenosine
triphosphate (ATP), which
is used as a source of
energy.
The Cell
circa 100 trillion (1014) cells in a human organism
200 different forms of cells
Nucleus only in
eukaryotic cells.
Contains most of the
cell's genetic material.
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Molecular Biology
... is the study of biology at a molecular level.
The field overlaps with other areas of biology, particularly genetics andbiochemistry
Molecular biology concerns itself with understanding the interactions
between the various systems of a cell, including the interrelationship ofDNA, RNA and protein synthesis and learning how these interactions areregulated.
Schematic relationship between biochemistry, genetics and molecular biology
Function
GenesProteins
Biochemistry
Molecular Biology
Genetics
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Biochemistry and Genetics
Biochemistry is the study of molecules (e.g.proteins). Biochemists take an organism or cell anddissect it into its molecular components, such asenzymes, lipids and DNA, and reconstitute them intest tubes (in vitro).
Genetics is the study of the effect of geneticdifferences on organisms. Often this can beinferred by the absence of a normal component
(e.g. one gene).
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From Genes to Proteins
DNA
mRNA
Protein
Gen
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The Human Genome -- 26 June 2000
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DNA
~6 billion base pairs
in every cell build the
human genome
genes form only 1,5% of
the human genome
a gene is a segment ofthe DNA, that encodes
the constructon plan for a
protein
in humans there are ca.30,000 genes only
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Chromosome
81,691,216157617
89,995,999109816
100,114,055112215
105,311,216109814
114,151,65674813
133,464,434165212
134,978,784209311
135,480,874144010
134,505,81912999
145,908,73811278
158,431,29914437
170,740,54119636
180,967,29516435
191,610,52312974
199,411,73120323
243,315,02822882
245,203,89829681
BasesGenesChrom.
A chromosome is a very long, continuous piece of DNA, which contains many
genes, regulatory elements and other intervening nucleotide sequences.
50,961,097231Y
152,634,1661184X
49,476,97228822
46,976,53730321
63,644,86892720
63,790,860145419
77,753,51076618
BasesGenesChrom.
http://www.tqnyc.org/NYC040844/Mitosis.htm
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Chromosome
Karyogram of human female
~1200Fern (Farn)
42Wheat
~380Butterflies
40Pig
104Carp (Karpfen)
32Earthworm
78Chicken
24edible snail
64Horse16Dove (Taube)
54Sheep
16Guinea Pig
48Ape
14Rye (Roggen)
46Human
8Fruit Fly
# of chromosomesSpecies
http://www.answers.com/topic/human-karyogram-png
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DNA - Sequence
. . . . . acct c ct gt gcaaga acat gaaaca cct gt ggt t c t t cct t ct cc
t ggt ggcagc t cccagat gg gt cct gt ccc aggt gcacct gcaggagt cg
ggcccaggac t ggggaagcc t ccagagct c aaaaccccac t t ggt gacac
aact cacaca t gcccacggt gcccagagcc caaat ct t gt gacacacct c
ccccgt gccc acggt gccca gagcccaaat ct t gt gacac acct ccccca
t gcccacggt gcccagagcc caaat ct t gt gacacacct c ccccgt gccc
ccggt gccca gcacct gaac t ct t gggagg accgt cagt c t t cct ct t cc
ccccaaaacc caaggat acc ct t at gat t t cccggacccc t gaggt cacg
t gcgt ggt gg t ggacgt gag ccacgaagac cccgaggt cc agt t caagt ggt acgt ggac ggcgt ggagg t gcat aat gc caagacaaag ct gcgggagg
agcagt acaa cagcacgt t c cgt gt ggt ca gcgt cct cac cgt cct gcac
caggact ggc t gaacggcaa ggagt acaag t gcaaggt ct ccaacaaagc
aaccaagt ca gcct gacct g cct ggt caaa ggct t ct acc ccagcgacatcgccgt ggag t gggagagca at gggcagcc ggagaacaac t acaacacca
cgcct cccat gct ggact cc gacggct cct t ct t cct ct a cagcaagct c
accgt ggaca agagcaggt g gcagcagggg aacat ct t ct cat gct ccgt
gat gcat gag gct ct gcaca accgct acac gcagaagagc ct ct c. . . . .
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DNA - Deoxyribonucleic acid
Deoxyribonucleic acid (DNA) forms adouble stranded helix.
A sugar-phosphate backbone forms the
outer shell on the helix
The two strands of DNA run in oppositedirections.
Bases face towards each other and formhydrogen bonds
carries the generic instructions (genes)
Nucleic acids
Cytosine - C
Guanine - G
Adenine - A
Thymine - T
complementary base pairs
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DNA - Deoxyribonucleic acid
A nucleotide is an organic molecule build of three components:
one out of five bases (A, G, C, T and U in RNA), a pentose sugar
(deoxyribose in DNA or ribose in RNA) and a phosphate group.
Nucleoside = Nucleobase + Pentose
Nucleotide = Nucleobase + Pentose + Phosphate Group
Thymidin monophosphate (TMP)ThymidinThymine (T)
Cytidine monophosphate (CMP)CytidinCytosine (C)
Guanosine monophosphate (GMPGuanosinGuanine (G)
Adenosine monophosphate (AMP)AdenosineAdenine (A)
nucleotidenucleosidefree base
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DNA - Deoxyribonucleic acid
GMP
HO
OH
O
P O
HO
ONH2N
N
N NH
NH2
CMP
HO
OH
O
P O
HO
O
NH2
N N
O
TMP
HO
OH
O
P O
HO
O
O
N NH
CH3
O
HO
OH
O
P O
HO
ONH2N
N
N N
AMP
PhosphateSugar
Base
12
54
3
1
2
54
3
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DNA
C G C T
S S S S
P P P P P
P P P P P
S S S S
C G C T
G C G A
S S S S
P P P P PSugar Phosphate Backbone
Base pairhydrogen bond
base
sugar
phosphate
5
3
3
5
[read as 3 prime and 5 prime]
A
T
A
T
C
G
T
A
C
G
C
G
T
A
G
C
A
T
G
C
T
C
A
T
T
A
C
G
C
G
A
T
G
C
G
C
T
A
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DNA - Molecule
CCTAGACATTGCTTTCCCATCCTGCTACTCAATGACAGTTTCTGGTTTCACTGGGTCACTCTCATCTTGATGCACTCCCGGGCAAGAGCTAACTGAAAGGCAGCTGCGTAACACATACCA GACACAACAGTTTATCATGGGAGAGTGAATTAAACCAGGAA...
DNA-sequence (Alphabet: ATGC)
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RNA Ribonucleic acid
In RNA the base Thymine (T) is replaced by Uracil (U). The other difference
to DNA is that the sugar (Pentose) will be Ribose instead of Deoxiribose.
Ribose has an additional hydroxyl group.
Bases:
Cytosine - C
Guanine - G
Adenine - A
Uracil - U
Uracil
RNA transmits genetic information from DNA (via transcription) into
proteins (by translation).
RNA is almost exclusively found in the single-stranded form.
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RNA Ribonucleic acid
RNA plays several roles in biology:
Messenger RNA (mRNA) is transcribed directly from a gene's DNA and is used to
encode proteins.
RNA genes are genes that encode functional RNA molecules; in contrast to mRNA,
these RNA do not code for proteins. The best-known examples of RNA genes are
transfer RNA (tRNA) and ribosomal RNA (rRNA). Both forms participate in the
process of translation, but many others exist.
RNA forms the genetic material (genomes) of some kinds of viruses.
Double-stranded RNA (dsRNA) is used as the genetic material of some RNA viruses
and is involved in some cellular processes, such as RNA interference.
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Proteins
Proteins have a variety of roles that they must fulfil:
1. they are the enzymes that rearrange chemical bonds.
2. they carry signals to and from the outside of the cell,and within the cell.
3. they transport small molecules.4. they form many of the cellular structures.
5. they regulate cell processes, turning them on and off
and controlling their rates.
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Proteins Amino Acids
there are 20 different types of amino acids (see below).
different sequences of amino acids fold into different 3-D
shapes.
Proteins can range from fewer than 20 to more than 5000
amino acids in length.
Each protein that an organism can produce is encoded in
a piece of the DNA called a gene.
the single-celled bacterium E.coli has about 4300
different genes.
Humans are believed to have about 30,000 different
genes (the exact number as yet unresolved),
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Proteins Amino Acids
Protein-Sequence(Alphabet:ACDEFGHIKLMNPQRSTVWY):
MENFQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEGVPSTAIREISLLK...
a typical human cell
contains about 100 million
proteins of about 10,000
types
CAT,CACHHistidine
TAA,TAG,TGA*Terminator (Stop)
CCT,CCC,CCA,CCGPProline
TGGWTryptophan
TAT,TACYTyrosine
TTT,TTCFPhenylalanine
CAA,CAGQGlutamine
AAT,AACNAsparagine
CGT,CGC,CGA,CGG,AGA,AGGRArginine
AAA,AAGKLysine
GAT,GAC,AAT,AACDAspartic Acid
GAA,GAGEGlutamic Acid
ATGMMethionine
TGT,TGCCCysteine
ACT,ACC,ACA,ACGTThreonine
TCT,TCC,TCA,TCG,AGT,AGCSSerine
ATT,ATC,ATAIIsoleucine
TTG,TTA,CTT,CTC,CTA,CTGLLeucine
GTT,GTC,GTA,GTGVValine
GCT,GCC,GCA,GCGAAlanine
GGT,GGC,GGA,GGGGGlycine
Triplet1-letter codeName
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Proteins Amino Acids
Properties of amino acids:
play a role in the construction of 3-D stuctures in proteins
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Proteins
Primary protein structure
is the sequence of a chain of amino acids
Secondary protein structure
occurs when the sequence of
amino acids are linked by hydrogen
bonds.
Tertiary protein st ructureoccurs when certain attractions
are present between alpha helices
and pleated sheets.
Quaternary protein st ructureis a protein consisting of more
than one amino acid chain.
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Proteins
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Proteins - Summary
DNA sequence determines protein
sequence Protein sequence determines protein
structure
Protein structure determines protein folding
and function
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Gene Expression
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Transcription
i k d
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Gene Expression - Transcription
Messenger RNA (mRNA)
Messenger RNA is RNA that carries information from DNA to the ribosome sites ofprotein synthesis in the cell.
Once mRNA has been transcribed from DNA, it is exported from the nucleus into the
cytoplasm, where it is bound to ribosomes and translated into protein.
Non-coding RNA or "RNA genes"
RNA genes (sometimes referred to as non-coding RNA or small RNA) are genes that
encode RNA that is not translated into a protein. The most prominent examples of RNA
genes are transfer RNA (tRNA) and ribosomal RNA (rRNA), both of which are involved in
the process of translation.
i t k d
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Translation
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Translation
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Translation
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Gene Expression - Translation
The genetic code is made up ofthree letter 'words' (termed a
codon) formed from a sequence of
three nucleotides (e.g.. ACT, CAG,
TTT).
These codons can then be
translated with messenger RNA
and then transfer
RNA, with a codon correspondingto a particular amino acid.
Since there are 64 possible
codons, most amino acids have
more than one possible codon.
There are also three 'stop' or
'nonsense' codons signifying the
end of the coding region.
CAT,CACHHistidine
TAA,TAG,TGA*Terminator
CCT,CCC,CCA,CCGPProline
TGGWTryptophan
TAT,TACYTyrosine
TTT,TTCFPhenylalanine
CAA,CAGQGlutamine
AAT,AACNAsparagine
CGT,CGC,CGA,CGG,AGA,AGGRArginine
AAA,AAGKLysine
GAT,GAC,AAT,AACDAspartic Acid
GAA,GAGEGlutamic Acid
ATGMMethionine
TGT,TGCCCysteine
ACT,ACC,ACA,ACGTThreonine
TCT,TCC,TCA,TCG,AGT,AGCSSerine
ATT,ATC,ATAIIsoleucine
TTG,TTA,CTT,CTC,CTA,CTGLLeucine
GTT,GTC,GTA,GTGVValine
GCT,GCC,GCA,GCGAAlanine
GGT,GGC,GGA,GGGGGlycine
Triplet1-Letter NicknameName
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A gene codes for a protein
CCTGAGCCAACTATTGATGAA
PEPTIDE
CCUGAGCCAACUAUUGAUGAA
www. .uni-rostock.deMetabolic networks
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next level of the functional/organisational hierarchy
Protein networks guide the biochemistry of living cellsProtein networks guide the biochemistry of living cells
Kegg database
(Japan)
www. .uni-rostock.deLevels of the functional/organizational
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Levels of the functional/organizational
hierarchy
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O l k i l
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Outlook coming lecture
Genomics
Proteomics
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Introduction to molecular and cell biologyIntroduction to molecular and cell biology
Thanks for your attention!