Introduction To Molecular and Cell Biology

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Bioinformatics
Introduction to molecular and cell biology
Ulf Schmitz
ulf.schmitz@informatik.uni-rostock.de
Bioinformatics and Systems Biology Group

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Ulf Schmitz, Introduction to molecular and cell biology
Outline
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1. 2. 3. 4.
Recommended Literature What is Bioinformatics? The Cell Molecular Biology / Genomics 1. Genes 2. DNA 3. RNA 4. Proteins 5. Gene Expression 5. Signaling Pathways 6. Outlook next lecture
Recommended Literature
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Developing Bioinformatics Computer Skills; Cynthia Gibas & Per Jambeck; OReilly; ISBN: 1565926641 New Biology for Engineers and Computer Scientists; Aydin Tzeren & Stephen W.Byers; Pearson Prentince Hall Bioengineering; ISBN: 0130664634 Bioinformatics: Sequence and Genome Analysis; David W. Mount; Cold Spring Harbor; ISBN: 0879697121 Introduction To Bioinformatics; Arthur M. Lesk; Oxford University Press ISBN: 0199277877
What is Bioinformatics?
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Bioinformatics: is the development and use of computer

applications for the Analysis, Interpretation, Simulation and Prediction of biological Systems and corresponding experimental methods in nature sciences.
What is Bioinformatics?
Biology Molecular Biology
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Chemistry
Medicine
Bioinformatics
Mathematics Statistics
Physics
Computer Science Informatics
History of Bioinformatics
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Biologists were searching for algorithms to analyze and interpret 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 where developed These efforts lead to the development of artificial neuronal networks, genetic algorithms and evolution strategies
Ulf Schmitz, Introduction to molecular and cell biology 6
Bioinformatics
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Offers an ever more essential input to

Molecular Biology Pharmacology (drug design) Agriculture Biotechnology Clinical medicine Anthropology Forensic science Chemical industries (detergent industries, etc.)
Organism, Organ, Cell

Organism
n Orga
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The Cell
The ER modifies proteins, makes macromolecules, and transfers substances throughout the cell.
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Nucleus only in eukaryotic cells. Contains most of the cell's genetic material.
Ribosome translates mRNA into a polypeptide chain (e.g., a protein).
Mitochondrion manufactures adenosine triphosphate (ATP), which is used as a source of energy.
circa 100 trillion (1014) cells in a human organism 200 different forms of cells
Molecular Biology

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... is the study of biology at a molecular level. 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.
Biochemistry
Function
Genetics
Proteins
Genes
Molecular Biology
Schematic relationship between biochemistry, genetics and molecular biology
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Biochemistry and Genetics
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Biochemistry is the study of molecules (e.g. proteins). Biochemists take an organism or cell and dissect it into its molecular components, such as enzymes, lipids and DNA, and reconstitute them in test tubes (in vitro). Genetics is the study of the effect of genetic differences on organisms. Often this can be inferred by the absence of a normal component (e.g. one gene).
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From Genes to Proteins

DNA
Gen
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mRNA
Protein
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The Human Genome -- 26 June 2000
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DNA
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~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 of the DNA, that encodes the constructon plan for a protein in humans there are ca. 30,000 genes only
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Chromosome
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A chromosome is a very long, continuous piece of DNA, which contains many genes, regulatory elements and other intervening nucleotide sequences.
Chrom. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Genes 2968 2288 2032 1297 1643 1963 1443 1127 1299 1440 2093 1652 748 1098 1122 1098 1576 Bases 245,203,898 243,315,028 199,411,731 191,610,523 180,967,295 170,740,541 158,431,299 145,908,738 134,505,819 135,480,874 134,978,784 133,464,434 114,151,656 105,311,216 100,114,055 89,995,999 81,691,216
http://www.tqnyc.org/NYC040844/Mitosis.htm
Chrom. 18 19 20 21 22 X Y
Genes 766 1454 927 303 288 1184 231
Bases 77,753,510 63,790,860 63,644,868 46,976,537 49,476,972 152,634,166 50,961,097
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Chromosome
Species
Fruit Fly Human Rye (Roggen) Ape Guinea Pig Sheep Dove (Taube) Horse edible snail Chicken Earthworm Carp (Karpfen) Pig Butterflies Wheat Fern (Farn)
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# of chromosomes
8 46 14 48 16 54 16 64 24 78 32 104 40 ~380 42 ~1200 Ulf Schmitz, Introduction to molecular and cell biology 16
Karyogram of human female
http://www.answers.com/topic/human-karyogram-png
DNA - Sequence
.....acctc tggtggcagc ggcccaggac aactcacaca ccccgtgccc tgcccacggt ccggtgccca ccccaaaacc tgcgtggtgg gtacgtggac agcagtacaa caggactggc aaccaagtca cgccgtggag cgcctcccat accgtggaca gatgcatgag ctgtgcaaga tcccagatgg tggggaagcc tgcccacggt acggtgccca gcccagagcc gcacctgaac caaggatacc tggacgtgag ggcgtggagg cagcacgttc tgaacggcaa gcctgacctg tgggagagca gctggactcc agagcaggtg gctctgcaca acatgaaaca gtcctgtccc tccagagctc gcccagagcc gagcccaaat caaatcttgt tcttgggagg cttatgattt ccacgaagac tgcataatgc cgtgtggtca ggagtacaag cctggtcaaa atgggcagcc gacggctcct gcagcagggg accgctacac
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cctgtggttc aggtgcacct aaaaccccac caaatcttgt cttgtgacac gacacacctc accgtcagtc cccggacccc cccgaggtcc caagacaaag gcgtcctcac tgcaaggtct ggcttctacc ggagaacaac tcttcctcta aacatcttct gcagaagagc
ttccttctcc gcaggagtcg ttggtgacac gacacacctc acctccccca ccccgtgccc ttcctcttcc tgaggtcacg agttcaagtg ctgcgggagg cgtcctgcac ccaacaaagc ccagcgacat tacaacacca cagcaagctc catgctccgt ctctc.....
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DNA - Deoxyribonucleic acid

Deoxyribonucleic acid (DNA) forms a double stranded helix. A sugar-phosphate backbone forms the outer shell on the helix The two strands of DNA run in opposite directions. Bases face towards each other and form hydrogen bonds carries the generic instructions (genes)
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Nucleic acids Cytosine - C Guanine - G Adenine - A Thymine - T
complementary base pairs
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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
free base Adenine (A) Guanine (G) Cytosine (C) Thymine (T)
nucleoside Adenosine Guanosin Cytidin Thymidin
nucleotide Adenosine monophosphate (AMP) Guanosine monophosphate (GMP Cytidine monophosphate (CMP) Thymidin monophosphate (TMP)
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AMP O HO P OH Phosphate O HO Sugar O N
N NH2 N N HO
GMP O
4
N NH2 N NH NH2
1
O 5 N
2
P OH
HO
Base CH3 O O
4
NH2 O 5 N
1 3 2
O HO P OH O HO
N O
NH HO
N O
P OH
HO CMP
TMP
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DNA
P P P P P C G C T S S S S
base
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S S S S
sugar
C G C T P P P P P
phosphate
G C G A S S S S
Sugar Phosphate Backbone
P P P P P 3
5 3
Base pair
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
hydrogen bond [read as 3 prime and 5 prime]
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DNA - Molecule
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DNA-sequence (Alphabet: ATGC) CCTAGACATTGCTTTCCCATCCTGCTACTCAATGACAGTTTCTGGTTTCACTGGG TCACTCTCATCTTGATGCACTCCCGGGCAAGAGCTAACTGAAAGGCAGCTGCGT AACACATACCA GACACAACAGTTTATCATGGGAGAGTGAATTAAACCAGGAA...
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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 Guanine Adenine Uracil
C G A U
Uracil
RNA transmits genetic information from DNA (via transcription) into proteins (by translation). RNA is almost exclusively found in the single-stranded form.
RNA Ribonucleic acid

RNA plays several roles in biology:
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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
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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
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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),

Name Glycine Alanine Valine Leucine Isoleucine Histidine Serine Threonine Cysteine Methionine Glutamic Acid Aspartic Acid Lysine Arginine Asparagine Glutamine Phenylalanine Tyrosine Tryptophan Proline Terminator (Stop) 1-letter code G A V L I H S T C M E D K R N Q F Y W P * Triplet GGT,GGC,GGA,GGG GCT,GCC,GCA,GCG GTT,GTC,GTA,GTG TTG,TTA,CTT,CTC,CTA,CTG ATT,ATC,ATA CAT,CAC TCT,TCC,TCA,TCG,AGT,AGC ACT,ACC,ACA,ACG TGT,TGC ATG GAA,GAG GAT,GAC,AAT,AAC AAA,AAG CGT,CGC,CGA,CGG,AGA,AGG AAT,AAC CAA,CAG TTT,TTC TAT,TAC TGG CCT,CCC,CCA,CCG TAA,TAG,TGA
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Protein-Sequence (Alphabet: ACDEFGHIKLMNPQRSTVWY): MENFQKVEKIGEGTYGVVY KARNKLTGEVVALKKIRLDT ETEGVPSTAIREISLLK...
a typical human cell contains about 100 million proteins of about 10,000 types
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Properties of amino acids: play a role in the construction of 3-D stuctures in proteins
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Proteins
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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 structure occurs when certain attractions are present between alpha helices and pleated sheets.
Quaternary protein structure is a protein consisting of more than one amino acid chain.
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Proteins
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Proteins - Summary
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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
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Gene Expression - Transcription
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Messenger RNA (mRNA) Messenger RNA is RNA that carries information from DNA to the ribosome sites of protein 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.
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Translation
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Translation
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Translation
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Gene Expression - Translation

Name Glycine 1-Letter Nickname G A V L I H S T C M E D K R N Q F Y W P *
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Triplet GGT,GGC,GGA,GGG GCT,GCC,GCA,GCG GTT,GTC,GTA,GTG TTG,TTA,CTT,CTC,CTA,CTG ATT,ATC,ATA CAT,CAC TCT,TCC,TCA,TCG,AGT,AGC ACT,ACC,ACA,ACG TGT,TGC ATG GAA,GAG GAT,GAC,AAT,AAC AAA,AAG CGT,CGC,CGA,CGG,AGA,AGG AAT,AAC CAA,CAG TTT,TTC TAT,TAC TGG CCT,CCC,CCA,CCG TAA,TAG,TGA
The genetic code is made up of

three 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 corresponding to 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.
Alanine Valine Leucine Isoleucine Histidine Serine Threonine Cysteine Methionine Glutamic Acid Aspartic Acid Lysine Arginine Asparagine Glutamine Phenylalanine Tyrosine Tryptophan Proline Terminator
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A gene codes for a protein
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CCTGAGCCAACTATTGATGAA
CCUGAGCCAACUAUUGAUGAA
PEPTIDE
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Metabolic networks
next level of the functional/organisational hierarchy
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Protein networks guide the biochemistry of living cells
Kegg database (Japan)

Levels of the functional/organizational hierarchy
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Outlook coming lecture
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Genomics Proteomics
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Introduction to molecular and cell biology
Thanks for your attention!
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Introduction To Molecular and Cell Biology

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Bioinformatics and Systems Biology Group

Ulf Schmitz, Introduction to molecular and cell biology

Ulf Schmitz, Introduction to molecular and cell biology

Ulf Schmitz, Introduction to molecular and cell biology

Bioinformatics: is the development and use of computer

Ulf Schmitz, Introduction to molecular and cell biology

Computer Science Informatics

Ulf Schmitz, Introduction to molecular and cell biology

Offers an ever more essential input to

Organism, Organ, Cell

Ulf Schmitz, Introduction to molecular and cell biology

Ribosome translates mRNA into a polypeptide chain (e.g., a protein).

Mitochondrion manufactures adenosine triphosphate (ATP), which is used as a source of energy.

Ulf Schmitz, Introduction to molecular and cell biology

Biochemistry and Genetics

Ulf Schmitz, Introduction to molecular and cell biology

From Genes to Proteins

Ulf Schmitz, Introduction to molecular and cell biology

The Human Genome -- 26 June 2000

Ulf Schmitz, Introduction to molecular and cell biology

Ulf Schmitz, Introduction to molecular and cell biology

Genes 766 1454 927 303 288 1184 231

Bases 77,753,510 63,790,860 63,644,868 46,976,537 49,476,972 152,634,166 50,961,097

Ulf Schmitz, Introduction to molecular and cell biology

Ulf Schmitz, Introduction to molecular and cell biology

DNA - Deoxyribonucleic acid

Nucleic acids Cytosine - C Guanine - G Adenine - A Thymine - T

complementary base pairs

Ulf Schmitz, Introduction to molecular and cell biology

DNA - Deoxyribonucleic acid

nucleoside Adenosine Guanosin Cytidin Thymidin

Ulf Schmitz, Introduction to molecular and cell biology

DNA - Deoxyribonucleic acid

AMP O HO P OH Phosphate O HO Sugar O N

Ulf Schmitz, Introduction to molecular and cell biology

Sugar Phosphate Backbone

hydrogen bond [read as 3 prime and 5 prime]

Ulf Schmitz, Introduction to molecular and cell biology

DNA-sequence (Alphabet: ATGC) CCTAGACATTGCTTTCCCATCCTGCTACTCAATGACAGTTTCTGGTTTCACTGGG TCACTCTCATCTTGATGCACTCCCGGGCAAGAGCTAACTGAAAGGCAGCTGCGT AACACATACCA GACACAACAGTTTATCATGGGAGAGTGAATTAAACCAGGAA...

Ulf Schmitz, Introduction to molecular and cell biology

RNA Ribonucleic acid

RNA Ribonucleic acid

Ulf Schmitz, Introduction to molecular and cell biology

Ulf Schmitz, Introduction to molecular and cell biology

Proteins Amino Acids

Proteins Amino Acids

Protein-Sequence (Alphabet: ACDEFGHIKLMNPQRSTVWY): MENFQKVEKIGEGTYGVVY KARNKLTGEVVALKKIRLDT ETEGVPSTAIREISLLK...

Ulf Schmitz, Introduction to molecular and cell biology

Proteins Amino Acids

Ulf Schmitz, Introduction to molecular and cell biology

Primary protein structure is the sequence of a chain of amino acids

Ulf Schmitz, Introduction to molecular and cell biology

Ulf Schmitz, Introduction to molecular and cell biology

Ulf Schmitz, Introduction to molecular and cell biology

Ulf Schmitz, Introduction to molecular and cell biology

Ulf Schmitz, Introduction to molecular and cell biology

Gene Expression - Transcription

Ulf Schmitz, Introduction to molecular and cell biology

Ulf Schmitz, Introduction to molecular and cell biology

Ulf Schmitz, Introduction to molecular and cell biology

Ulf Schmitz, Introduction to molecular and cell biology