21 st Century = Biotech Century - PowerPoint PPT Presentation

21 st century biotech century n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
21 st Century = Biotech Century PowerPoint Presentation
Download Presentation
21 st Century = Biotech Century

play fullscreen
1 / 66
21 st Century = Biotech Century
531 Views
Download Presentation
DoraAna
Download Presentation

21 st Century = Biotech Century

- - - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

  1. 21st Century = Biotech Century • Completion of human genome • High-throughput microarray and similar devices • Cloning • Genetic engineering • Computational power Everyone is moving towards Biotech CS 6463: An overview of Molecular Biology

  2. 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 CS 6463: An overview of Molecular Biology

  3. 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 CS 6463: An overview of Molecular Biology

  4. Objective Basic 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 CS 6463: An overview of Molecular Biology

  5. Communication is important CS 6463: An overview of Molecular Biology

  6. Textbooks and course website • Required textbooks: • Molecular Biology of the Cell (Main text) • Bioinformatics, Genomics and Proteomics (Lab) • Other material • References: • Human Molecular Genetics (2nd 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 CS 6463: An overview of Molecular Biology

  7. 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, Human Genome (HuGe) lab meets to discuss current bioinformatics issues. All are welcome even if you are new to bioinformatics (but are taking this course). CS 6463: An overview of Molecular Biology

  8. Database Search CS 6463: An overview of Molecular Biology

  9. Course Organization Overview of Molecular Biology (and project discussion) Databases • Introduction to Cell: • Cells and Genomes • Cell Chemistry and Biosynthesis • Proteins Gene finding Motif finding Data preprocessing Classification problem Clustering problem Microarray analysis Basic Genetic Mechanisms 4. DNA and Chromosomes 6. From DNA to Protein 7. Control of gene expression Sequence alignment Hidden Markov Model Diseases: 23. Cancer 25. Pathogens Others: SNP, NRAi Bioinformatics/Computational Biology Molecular Biology CS 6463: An overview of Molecular Biology

  10. 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. CS 6463: An overview of Molecular Biology

  11. 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. CS 6463: An overview of Molecular Biology

  12. 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. CS 6463: An overview of Molecular Biology

  13. 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 CS 6463: An overview of Molecular Biology

  14. A.1 Background: Procaryotic and Eukaryotic Cells • Two types of cells: • Prokaryotic (bacteria) • Eukaryotic (multicellular organisms, • Ameba) CS 6463: An overview of Molecular Biology

  15. A.1 Background: Procaryotic and Eukaryotic Cells http://www-class.unl.edu/bios201a/spring97/group6/ CS 6463: An overview of Molecular Biology

  16. 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+, Ca2+, 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 10-12cm, Mammal: 4 x 10-9cm] • Relative Volume: [E. Coli: Mammal = 1: 2000] CS 6463: An overview of Molecular Biology

  17. A.2 Building Blocks: Structure of bases, nucleosides and nucleotides Purines: DNA: ‘polymer of A, G, T, C’ RNA: ‘polymer of A, G, U (replace T), C’ Pyrimidines: base sugar CS 6463: An overview of Molecular Biology

  18. A.2. Building Blocks: Common bases found in nucleic acids CS 6463: An overview of Molecular Biology

  19. A.2 Building Blocks: 20 amino acids Polypeptides: chains of amino acids Carboxyl group Amino group CS 6463: An overview of Molecular Biology

  20. A.2. Building Blocks: Abbreviation of Amino Acids CS 6463: An overview of Molecular Biology

  21. A.2. Building blocks: Properties of Amino Acids I http://www.russell.embl-heidelberg.de/aas/aas.html CS 6463: An overview of Molecular Biology

  22. 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. CS 6463: An overview of Molecular Biology

  23. 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, CS 6463: An overview of Molecular Biology

  24. 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 CS 6463: An overview of Molecular Biology

  25. A.3 DNA Structure: The Phosphodiester Bond CS 6463: An overview of Molecular Biology

  26. A.3 DNA Structure: base pairing (Watson-Crick Rule). CS 6463: An overview of Molecular Biology

  27. A.3 DNA Structure: DNA is a double-stranded anti-parallel helix • %GC = 40%? How many % is G? C? A? T? Complementary DNA (cDNA) downstream upstream http://www.sumanasinc.com/webcontent/anisamples/molecularbiology/DNA_structure.html CS 6463: An overview of Molecular Biology

  28. A.3 DNA Structure: DNA is a double-stranded anti-parallel helix CS 6463: An overview of Molecular Biology

  29. A.3 DNA Structure: RNA structure palindrome CS 6463: An overview of Molecular Biology

  30. 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) CS 6463: An overview of Molecular Biology

  31. A.4 DNA Structure: The Central Dogma Old 1-directional model CS 6463: An overview of Molecular Biology

  32. 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 CS 6463: An overview of Molecular Biology

  33. A.4 Transcription and Gene Expression:Transcription intron intron exon exon exon Pre-mRNA 5’ UTR start stop 3’ UTR poly A (complementary nucleotides) (2nd key, May not be there) (1st key) intron intron exon exon exon promoter 5’ UTR start stop 3’ UTR TFBS TFBS 5’ 3’ (almost always there) (mostly for non-housing gene) cap TFBS – Transcription factor binding site pore Nuclear membrane CS 6463: An overview of Molecular Biology

  34. A.4 Transcription and Gene Expression:Gene Regulation G C G A G T C U C A G http://henge.bio.miami.edu/mallery/movies/transcription.mov http://www-class.unl.edu/biochem/gp2/m_biology/animation/gene/gene_a2.html CS 6463: An overview of Molecular Biology

  35. 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. CS 6463: An overview of Molecular Biology

  36. A.4 Transcription and Gene Expression: Trans- and cis-elements Important: If pattern is there, does not necessary mean it is a cis-element. CS 6463: An overview of Molecular Biology

  37. A.4 Transcription and Gene Expression: Promoters Start from 1 not 0 CS 6463: An overview of Molecular Biology

  38. A.4 Transcription and Gene Expression: Enhancers and Silencers (Transcription Factors) Many basepairs away CS 6463: An overview of Molecular Biology

  39. 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 (CH3) • Transcription factors’ expression levels are low. • Microarrays measure the expression levels of genes CS 6463: An overview of Molecular Biology

  40. 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 CS 6463: An overview of Molecular Biology

  41. A.4 Transcription and Gene Expression:Transcription intron intron exon exon exon Pre-mRNA 5’ UTR start stop 3’ UTR poly A (complementary nucleotides) (2nd key, May not be there) (1st key) intron intron exon exon exon promoter 5’ UTR start stop 3’ UTR TFBS TFBS 5’ 3’ (almost always there) (mostly for non-housing gene) cap exon exon exon 5’ UTR start stop 3’ UTR poly A Massager RNA (mRNA) pore Nuclear membrane Splicing the introns: http://www.sumanasinc.com/webcontent/anisamples/molecularbiology/mRNAsplicing.html CS 6463: An overview of Molecular Biology

  42. A.5 RNA Processing: RNA Splicing acceptor donor GT-AG spliceosome AT-AC spliceosome (rare) CS 6463: An overview of Molecular Biology

  43. A.5 RNA Processing: Consensus Sequences at splice donor, acceptor and branch sites CS 6463: An overview of Molecular Biology

  44. 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 CS 6463: An overview of Molecular Biology

  45. A.5 RNA Processing: 5’ End Capping CS 6463: An overview of Molecular Biology

  46. A.5 RNA Processing: 3’ end polyadenylated. CS 6463: An overview of Molecular Biology

  47. 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 CS 6463: An overview of Molecular Biology

  48. A.5 RNA Processing: Example of the human b-globin gene CS 6463: An overview of Molecular Biology

  49. A.4 RNA Processing: Export out of the nuclear CS 6463: An overview of Molecular Biology

  50. 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 CS 6463: An overview of Molecular Biology