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BiologyOverview.ppt BiologyOverview.ppt Presentation Transcript

  • 21 st Century = Biotech Century
    • Completion of human genome
    • High-throughput microarray and similar devices
    • Cloning
    • Genetic engineering
    • Computational power
    Everyone is moving towards Biotech
  • Explosive growth of biological data
    • Biology is becoming more computational intensive. High throughput bioinformatics, Lots of data
      • The Molecular Biology Database Collection: 2005 update
    • Small excerpt from the A's:
      • AARSDB: Aminoacyl-tRNA synthetase sequences
      • ABCdb: ABC transporters
      • AceDB: C. elegans, S. pombe, and human sequences and genomic information
      • ACTIVITY: Functional DNA/RNA site activity
      • ALFRED: Allele frequencies and DNA polymorphisms
  • Opportunities for CS
    • Possibilities for CS contributions
      • Data integration problem
      • Data extraction from literature (natural language processing)
      • Database issues (including automation)
      • Visualization
      • Mining large complex data sets
  • Objective
    • Introduction to basic molecular biology to computer science students by a computer scientist.
    • A survey of databases: NCBI, SwissProt, PDB, Transfac, …
    • Introduction to computational techniques in analyzing genomics (and proteomics) data
    Basic
  • Communication is important
  • Textbooks and course website
    • Required textbooks:
      • Molecular Biology of the Cell (Main text)
      • Bioinformatics, Genomics and Proteomics (Lab)
      • Other material
    • References:
      • Human Molecular Genetics (2 nd Edition available for free)
      • Data Mining : Practical Machine Learning Tools and Techniques with Java Implementations (The Morgan Kaufmann Series in Data Management Systems) by Ian H. Witten, Eibe Frank (Paperback)
      • Microarrays for an Integrative Genomics (Computational Molecular Biology) [Paperback] By: Isaac S. Kohane, et al
      • Molecular Biology Web Book
    • Course website: http://www.cs.utsa.edu/~kwek/cs6463f05.html
  • Intended Audience
    • CS graduate students with an interest in bioinformatics or want to explore bioinformatics. High School Biology.
    • Not for students who want to find a filler class in between classes.
    • Every Tuesday noon to 1pm, Hu man Ge nome (HuGe) lab meets to discuss current bioinformatics issues. All are welcome even if you are new to bioinformatics (but are taking this course).
  • Database Search
  • Course Organization Overview of Molecular Biology (and project discussion) Databases
    • Introduction to Cell:
    • Cells and Genomes
    • Cell Chemistry and Biosynthesis
    • Proteins
    Data preprocessing Classification problem Clustering problem Microarray analysis Sequence alignment Hidden Markov Model Basic Genetic Mechanisms 4. DNA and Chromosomes 6. From DNA to Protein 7. Control of gene expression Diseases: 23. Cancer 25. Pathogens Others: SNP, NRAi Gene finding Motif finding Bioinformatics/Computational Biology Molecular Biology
  • Project
    • Grade distributions
      • 1 Quiz – 10%
      • 2 tests – 30%
      • Homework and Lab – 10%
      • Project – 50% (+ 10% bonus)
    • Project
      • Serious in bioinformatics (all HuGe Lab members): Mini (NIH-) proposal project. Besides preliminary results, a proposal for future work (i.e. independent studies, theses). Possible collaborations with UTHSCSA and others.
        • Specific Aim(s): What do you want to do? Why is it important?
        • Background: What have been done previously? (What make you approach interesting?) Where do you get your data?
        • (Preliminary) Result: To elaborate later.
        • Future Work: To elaborate later.
      • A project: Same as above except do not need to have future work.
    • Office hours (for projects): By appointment (send me an email 24 hours before) Tu, Th 10-3, 5-7, 8:30-10. W 10:30-noon.
  • Some Important Dates
    • September 13: Quiz 1 (there will be a second chance quiz)
    • September 20: Specific aim of project due. [1 meeting to discuss with me]
    • October 27: Test 1
    • October 18: Background of project due. (you must already started doing experiments) [2 meetings to discuss with me]
    • November 24: Test 2
    • December 10: Final report of project. [2 meetings to discuss with me]
    • IMPORTANT: if you do not meet me the require number of times, I am not accepting your report. Also, each meeting should be at least one week a part.
  • Your Responsibility
    • Read the assigned reading once the material is covered in lecture. Lecture is to make your reading easier.
    • Try printing out the slides to take notes.
    • Project: Observe the deadline!!!! Come and talk to me.
  • A. An overview of molecular biology
    • Read Human Molecular Genetic Ch. 1
    • A.1. Background
    • A.2. Macromolecules
    • A.3. DNA structure
    • A.4. RNA transcription and Gene Expression
    • A.5. RNA processing
    • A.6. Translation, post-translation processing and protein structure
    • A.7. Project ideas
    • Two types of cells:
    • Prokaryotic (bacteria)
    • Eukaryotic (multicellular organisms,
    • Ameba, E. Coli)
    A.1 Background: Procaryotic and Eukaryotic Cells
  • A.1 Background: Procaryotic and Eukaryotic Cells http://www-class.unl.edu/bios201a/spring97/group6/
  • A.2. Building Blocks: Chemical Composition of Eukaryotic Cell
    • Water [E. Coli: 70%, Mammalian Cell: 70%]
    • Macro-molecules:
      • DNA: Deoxyribonucleic Acid [E. Coli: 1%, Mammal: 0.25%]
      • RNA: Ribonucleic Acid [E. Coli: 6%, Mammal: 1.1%]
      • Proteins [E. Coli: 15%, Mammal: 18%]
    • Inorganic ions: Na + , K + , Mg + , Ca 2+ , Cl - [E. Coli: 1%, Mammal: 1%]
    • Lipids:
      • Phospholipids [E. Coli: 2%, Mammal: 3%]
      • Other lipids [E. Coli: -, Mammal: 0.2%]
    • Polysaccahrides [E. Coli: 1%, Mammal: 0.25%]
    • Volume: [E. Coli: 2 x 10 -12 cm, Mammal: 4 x 10 -9 cm]
    • Relative Volume: [E. Coli: Mammal = 1: 2000]
  • A.2 Building Blocks: Structure of bases, nucleosides and nucleotides DNA: ‘polymer of A, G, T, C’ RNA: ‘polymer of A, G, U (replace T), C’ sugar base Purines: Pyrimidines:
  • A.2. Building Blocks: Common bases found in nucleic acids
  • A.2 Building Blocks : 20 amino acids Polypeptides: chains of amino acids Amino group Carboxyl group
  • A.2. Building Blocks: Abbreviation of Amino Acids (CH3)2-CH-CH(NH2)-COOH val V Valine HO-Ph-CH2-CH(NH2)-COOH tyr Y Tyrosine Ph -NH-CH= C -CH2-CH(NH2)-COOH trp W Tryptophan CH3-CH(OH)-CH(NH2)-COOH thr T Threonine HO-CH2-CH(NH2)-COOH ser S Serine N H-(CH2)3- C H-COOH pro P Proline Ph-CH2-CH(NH2)-COOH phe F Phenylalanine CH3-S-(CH2)2-CH(NH2)-COOH met M Methionine H2N-(CH2)4-CH(NH2)-COOH lys K Lysine (CH3)2-CH-CH2-CH(NH2)-COOH leu L Leucine CH3-CH2-CH(CH3)-CH(NH2)-COOH ile I Isoleucine N H-CH=N-CH= C -CH2-CH(NH2)-COOH his H Histidine NH2-CH2-COOH gly G Glycine H2N-CO-(CH2)2-CH(NH2)-COOH gln Q Glutamine HOOC-(CH2)2-CH(NH2)-COOH glu E Glutamic Acid HS-CH2-CH(NH2)-COOH cys C Cysteine HOOC-CH2-CH(NH2)-COOH asp D Aspartic Acid H2N-CO-CH2-CH(NH2)-COOH asn N Asparagine HN=C(NH2)-NH-(CH2)3-CH(NH2)-COOH arg R Arginine CH3-CH(NH2)-COOH ala A Alanine Linear Structure Abbreviation Name
  • A.2. Building blocks: Properties of Amino Acids I http://www.russell.embl-heidelberg.de/aas/aas.html
  • A.2. Building blocks: Some Terms for describing Properties of Amino Acids
    • Hydrophobic amino acids are those with side-chains that do not like to reside in an aqueous (i.e. water) environment.
    • Polar amino acids are those with side-chains that prefer to reside in an aqueous (i.e. water) environment.
    • Strictly speaking, aliphatic implies that the protein side chain contains only carbon or hydrogen atoms.
    • A side chain is aromatic when it contains an aromatic ring system.
  • A.2 Building Blocks: Covalent and Non-covalent Bonds
    • Covalent bonds : stronger. Nucleic acid and protein polymers are from by covalent binds connecting nucleotides and amino acids (respectively) to form a linear backbone
    • Non-covalent bonds : weaker and revisible. 4 types:
      • Hydrogen bonds : N – H –O [double-stranded DNA, protein folding, …etc
      • Ionic bonds : Ionic interaction between charged group, sat Na+ and Cl-
      • Van der Waals : Optimum attraction between two atoms.
      • Hydrophobic forces : Water is polar molecules,
  • A. An overview of molecular biology
    • A.1. Background
    • A.2. Building Blocks of Macromolecules
    • A.3. DNA structure
    • A.4. RNA transcription and Gene Expression
    • A.5. RNA processing
    • A.6. Translation, post-translation processing and protein structure
    • A.7. Project ideas
  • A.3 DNA Structure: The Phosphodiester Bond
  • A.3 DNA Structure: base pairing (Watson-Crick Rule).
  • A.3 DNA Structure: DNA is a double-stranded anti-parallel helix
    • %GC = 40%? How many % is G? C? A? T?
    http://www.sumanasinc.com/webcontent/anisamples/molecularbiology/DNA_structure.html upstream downstream Complementary DNA (cDNA)
  • A.3 DNA Structure: DNA is a double-stranded anti-parallel helix
  • A.3 DNA Structure: RNA structure palindrome
  • A.3 DNA Structure: Viral Genomes
    • Highly Variable:
      • DNA or RNA
      • Single stranded or double stranded
      • Linear or Circular
      • Segmented and Multipartite
    • Virus normally replicate in the cytosol. Unusal Retrovirus duplicate itself in the nucleus (using reverse transcriptase)
  • A.4 DNA Structure: The Central Dogma Old 1-directional model
  • A. An overview of molecular biology
    • A.1. Background
    • A.2. Building Blocks of Macromolecules
    • A.3. DNA structure
    • A.4. RNA transcription and Gene Expression
    • A.5. RNA processing
    • A.6. Translation, post-translation processing and protein structure
    • A.7. Project ideas
  • A.4 Transcription and Gene Expression:Transcription exon exon exon intron intron start stop 5’ UTR 3’ UTR promote r TFBS 5’ 3’ (1 st key) Nuclear membrane (2 nd key, May not be there) cap pore TFBS (almost always there) (mostly for non-housing gene) TFBS – Transcription factor binding site exon exon exon intron intron start stop 5’ UTR 3’ UTR (complementary nucleotides) Pre-mRNA poly A
  • A.4 Transcription and Gene Expression:Gene Regulation http:// henge.bio.miami.edu/mallery/movies/transcription.mov http://www-class.unl.edu/biochem/gp2/m_biology/animation/gene/gene_a2.html A G T C U C A G G C G
  • A.4 Transcription and Gene Expression:RNA Polymerase
    • There are three classes of RNA Polymerases:
      • Polymerase I: Localized in the nucleolus. Transcribe rRNA (ribosome RNA) 28S, 18S 5.8S rRNA.
      • Polymerase II: All protein-coding genes most smRNAs. Unique in capping and polyadenylation.
      • Polymerase III: tRNA, other rRNAs, snRNAs. [The promoter can be downstream]
    • Pusedo-genes (gene fragments): Previously were genes
    • Only 2% of the human genome encode proteins.
  • A.4 Transcription and Gene Expression: Trans- and cis-elements Important: If pattern is there, does not necessary mean it is a cis-element. CREB/ATF family GTGACGT(A/C)A(A/G) CRE (cAMP response element) AP-1 family (many) GTGAGT(A/C)A TRE Many CCAAT CAAT Box TFIID (TFIIA – stabilize it) TATAA TATA Box Spl GGGCGG GC Box Trans-acting Factor DNA sequence Cis- element
  • A.4 Transcription and Gene Expression: Promoters Start from 1 not 0
  • A.4 Transcription and Gene Expression: Enhancers and Silencers (Transcription Factors) Many basepairs away
  • A.4 Transcription and Gene Expression: Tissue Specific Genes
    • House keeping genes: Genes encoding histone protein, ribosome protein. Always on.
    • Tissue or development-specific (non-housekeeping) genes:
      • Transcriptional inactive chromatin
      • Methylation of Cytosine, replacing a hydrogen (H) with methyl (CH 3 )
      • Transcription factors’ expression levels are low.
    • Microarrays measure the expression levels of genes
  • A. An overview of molecular biology
    • A.1. Background
    • A.2. Building Blocks of Macromolecules
    • A.3. DNA structure
    • A.4. RNA transcription and Gene Expression
    • A.5. RNA processing
    • A.6. Translation, post-translation processing and protein structure
    • A.7. Project ideas
  • A.4 Transcription and Gene Expression:Transcription exon exon exon intron intron start stop 5’ UTR 3’ UTR promote r TFBS 5’ 3’ (1 st key) Nuclear membrane (2 nd key, May not be there) Splicing the introns: http://www.sumanasinc.com/webcontent/anisamples/molecularbiology/mRNAsplicing.html exon exon exon start stop 5’ UTR 3’ UTR Massager RNA (mRNA) poly A cap pore TFBS (almost always there) (mostly for non-housing gene) exon exon exon intron intron start stop 5’ UTR 3’ UTR (complementary nucleotides) Pre-mRNA poly A
  • A.5 RNA Processing: RNA Splicing donor acceptor GT-AG spliceosome AT-AC spliceosome (rare)
  • A.5 RNA Processing: Consensus Sequences at splice donor, acceptor and branch sites
  • A.5 RNA Processing: Mechanism of RNA Splicing (GU-AG introns) Splicesome (5 snRNA) http://www.nature.com/nrn/journal/v2/n1/animation/nrn0101_043a_swf_MEDIA1.html
  • A.5 RNA Processing: 5’ End Capping
  • A.5 RNA Processing: 3’ end polyadenylated.
  • A.5 RNA Processing: Functions of 5’ End Cap and Poly A tail
    • Functions of 5’ end cap
    • Prevent mRNA molecules degradation.
    • Facilitate transport to cytoplasm
    • RNA splicing
    • Facilitate translation
    • Function of 3’ end poly(A) tail
    • 1. Facilitate transport to cytoplasm
    • 2. Stabilize the mRNA in the cytoplasm
    • 3. Facilitate translation
  • A.5 RNA Processing: Example of the human  -globin gene
  • A.4 RNA Processing: Export out of the nuclear
  • A. An overview of molecular biology
    • A.1. Background
    • A.2. Building Blocks of Macromolecules
    • A.3. DNA structure
    • A.4. RNA transcription and Gene Expression
    • A.5. RNA processing
    • A.6. Translation, post-translation processing and protein structure
    • A.7. Project ideas
  • A.5 RNA Processing: The Codon-anticodon Recognition http:// henge.bio.miami.edu/mallery/movies/translation.mov (almost always) tRNA
  • A.6 Translation and Post-Translational Processing : Peptide Bond Formation
  • A.6 Translation and Post-Translational Processing: The Genetic Codes N-terminal C-terminal
  • A.6 Translation and Post-Translational Processing: The Genetic Codes 64 possible codons: 1 Start codon AUG. 3 stop codons, 20 amino acids Signal in mRNAs can lead to alternative interpretation of stop codons: UGA  21 st AA selencocysteine, UAG  22 nd AA pyrrolysine. wobble - mitochondrial
  • A.6 Translation and Post-Translational Processing: Multiple Post-Translational Cleavages of Polypeptide Precursors
  • A.6 Translation and Post-Translational Processing: Protein Secondary Structure
  • A.6 Translation and Post-Translational Processing: Quaternary Amino acid sequence  secondary structure  tertiary structure Amino acid sequence
  • A.6 Translation and Post-Translational Processing: Quaternary Structure
  • A.6 Translation and Post-Translational Processing: Disulfide Bridges
  • A.6 Translation and Post-Translational Processing: Post-translational Modification
    • http:// www.ncbi.nlm.nih.gov/books/bv.fcgi?rid =hmg.table.103
  • A.6 Translation and Post-Translational Processing: Protein Sorting (Localization) 1. Signal Peptide 2. Post-translational modification Addition of mannose 6-phosphate residues Lysosome Internal sequence of amino acids. Often a string of basic amino acids plus prolines; maybe bipartite. Nucleus N-terminal peptide, a-helix. One side hydrophilic and one side hydrophobic Mitochondria N-terminal peptide of 20 or so very hydrophobic AAs. Endoplasmic reticulum and secretion from cell (Typical) Location and form of signal Protein Destination
  • A.6 Translation and Post-Translational Processing: Cellular Function of Proteins
    • Diverse cellular functions:
      • Enzymes – ‘cut things into pieces’
      • Receptors
      • Transport
      • Transcription factor
      • Signaling
      • Hormones
      • Strutural
      • .. etc
  • A. An overview of molecular biology
    • A.1. Background
    • A.2. Building Blocks of Macromolecules
    • A.3. DNA structure
    • A.4. RNA transcription and Gene Expression
    • A.5. RNA processing
    • A.6. Translation, post-translation processing and protein structure
    • A.7. Project ideas
  • A.7 Summary: Central Dogma Simplify Enzymes, Receptors, ... etc
  • A.7 Summary: Don’t forget about mitochondria!
  • A.7 Summary: Life is more complex