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Biology Tutorial

Biology Tutorial. Aarti Balasubramani Anusha Bharadwaj Massa Shoura Stefan Giovan. Viruses. A T4 bacteriophage injecting DNA into a cell. Influenza A virus.

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Biology Tutorial

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  1. Biology Tutorial AartiBalasubramani AnushaBharadwaj Massa Shoura Stefan Giovan

  2. Viruses A T4 bacteriophage injecting DNA into a cell. Influenza A virus Electron micrograph of HIV. Cone-shaped cores are sectioned in various orientations. Viral genomic RNA is located in the electron-dense wide end of core. http://stc/istc.nsf/va_WebPages/InfluenzaEngPrint http://pathmicro.med.sc.edu

  3. Life Begins with Cells

  4. All cells are Prokaryotic or Eukaryotic http://course1.winona.edu/

  5. Eukaryotic Cell Endothelial cells under the microscope. Nuclei are stained blue with DAPI, microtubules are marked green by an antibody bound to FITC and actin filaments are labeled red with phalloidin bound to TRITC. Bovine pulmonary artery endothelial cells

  6. Cell Organelles Nucleus= contains the genetic material Mitochondrion= produces energy

  7. Golgi complex=protein distribution Endoplasmic Reticulum and Ribosomes=protein factory Lysosome=degradation http://microbewiki.kenyon.edu/

  8. Plasma Membrane

  9. DNA Replication Base Pairing A=T CG http://www.youtube.com/watch?v=teV62zrm2P0&feature=related

  10. Life Cycle of a Cell Cell division RNA and protein synthesis RNA and protein synthesis Resting cells DNA Replication

  11. The Central Dogma of Biology Replication

  12. Transcription http://www.youtube.com/watch?v=ztPkv7wc3yU

  13. Translation http://www.youtube.com/watch?v=-zb6r1MMTkc

  14. Outline • CellularBiology • Organelle Structure/Function • Central Dogma • Biochemistry • Energy Storage/Utilization • Macromolecules • Bioinformatics • Sequences and Databases • Alignments, Tree Building, Modeling

  15. Cells are Composed of a Molecular Hierarchy } Small molecules } Macromolecules } Supramolecular complexes

  16. BONDS, JUST BONDS • Covalent – nuclei share common electrons • STRONG!! • Non-Covalent – No common electrons • WEAK!! • Ionic • Non-Ionic http://publications.nigms.nih.gov/chemhealth/images/ch1_bonds.gif

  17. Macromolecular Structures are Stabilized by Weak Forces Strength, kJ mol-1 Distance Dependence Effective Range, nm Force Van der Waals interactions 0.4 - 4 0.2 Hydrogen bonds 4 - 48 0.3 Electrostatic interactions (unscreened) 20 - 50 5 - 50 <40 ? ? Hydrophobic interactions

  18. Hydrophobic Interactions Vibrational frequencies of O-H bond of H2O in ice, liquid H2O and CCl4 Structures formed by amphipathic molecules in H2O van Holde, Johnson & Ho Principles of Physical Biochemistry Prentice Hall, Upper Saddle River, NJ (1998)

  19. What Is DNA Made of? 5’ 3’

  20. DNA – The Double Helix

  21. Levels of Chromatin Packing

  22.   The Human Genome

  23. DNA to Amino Acids

  24. Amino Acids – Proteins Building Blocks

  25. The Making of a Polypeptide Chain

  26. The Four Levels of Protein Structure 3-dimensional folding of molecule Linear arrangement of monomeric unit Local regular structure Spatial arrangement of multiple subunits

  27. Single Nucleotide Mutations

  28. DNA Mutations

  29. Experimental Techniques

  30. Restriction Digestion

  31. Use of Restriction Digestion to Identify Mutations (a) Wild-type and mutant DNA sequences

  32. Gel Electrophoresis

  33. Gel Electrophoresis-Visualizing DNA

  34. The Polymerase Chain Reaction (PCR) 

  35. Cloning a human gene in a bacterial plasmid

  36. Outline • CellularBiology • Organelle Structure/Function • Central Dogma • Biochemistry • Energy Storage/Utilization • Macromolecules • Bioinformatics • Sequences and Databases • Alignments, Tree Building, Modeling

  37. Phenotype Tree Building How Related are Organisms? What do they eat? Where do they live? How do they divide? Move? Etc. Qualitative http://nai.arc.nasa.gov/seminars/68_Rivera/tree.jpg

  38. Genotype Tree Building How Related are Organisms? How similar is their genome? Proteome? MOLECULAR EVOLUTION Quantitative http://nai.arc.nasa.gov/seminars/68_Rivera/tree.jpg

  39. Comparison of Genomes • 1977- Φ-X174 genome sequenced • Only about 5.4 kbp • 1997- E. coli K-12 genome sequenced • About 4.6x103kbp • 2007- Watson’s Genome sequenced! • About 3x106kbp! • About 0.1% difference between human genomes and 1% difference between humans and chimps!

  40. Bioinformatics is… • Highly Interdisciplinary • Proteomics and Genomics • Structural and Computational Biology • Systems Biology • Computer Science, Probabilistic Modeling • Computational Sequence Analysis • What’s in a sequence? SEQUENCE STRUCTURE FUNCTION

  41. Power of Prediction • Can we … • predict structural and functional properties of proteins given its sequence? • predict the consequences of a mutation? • design proteins or drugs with specific functions? • Every thing we need to know is at our finger-tips, just need a better understanding of the natural world SEQUENCE STRUCTURE FUNCTION

  42. Protein Structure • Structure adopted is completely determined by sequence of residues • Compromise between comfort ( or ) and freedom () http://www.news.cornell.edu/stories/Aug06/protein_folding.jpg

  43. Secondary Structure Prediction • 2o structures form beneficial H-bonds (lower E) • -helices, -sheets • Dihedral angles (,) Source: Wikipedia

  44. Tertiary Structure Prediction • Homology/Comparative Modeling • BEST • Structure of very related protein is known • Fold Recognition/Threading • OFTEN IS ENOUGH • Similar folds available but no close relative • Knowledge Based or A Priori Predictions • ONLY POSSIBLE FOR VERY SHORT PROTEINS • Fold prediction but without experimental quality

  45. Sequence Alignments • FASTA Text Format >header – my sequence >header – my thesis THISISMYSEQ THESISTHYSTING • Alignment T H I S I S – M Y S E –Q – T H E S I S T H Y S T I NG • What can we learn from this?

  46. Alignments Dot plot of two subunits in Human Hemoglobin • Pairwise • Dot Plot • Global(N-W) or Local(S-W) • Simple Database Searches • FASTA/BLAST • Multiple Alignments • CLUSTAL • Advanced Strategies • PSI/PHI-BLAST, HMM’s Alpha Chain Beta Chain

  47. Databases • Nucleotide Sequence Database Collaboration • DDBJ, EMBL, GenBankat NCBI • Amino Acid Databases • UniProt, SWISS-PROT, TrEMBL • Structural • PDB, MMDB, MSD • Very Many Derivations! http://www.ncbi.nlm.nih.gov/Database/

  48. Scoring Matrices • PAM Matrix : Point Accepted Mutation • PAM1 estimates substitution rate if 1% of AA had changed. Standards: PAM30 and PAM60 • BLOSUM : BLOcks of Amino Acid SUbstitutionMatrix • BLOSUM80 “blocks” together sequences with greater then 80% similarity. PAM250 BLOSUM45 PAM1 BLOSUM80 Less Divergent More Divergent

  49. FASTA and BLAST • FASTA - FASTAll, Rapid AA or NT Alignments • BLAST – Basic Local Alignment Search Tool • Scoring Alignments • Raw and Bit Scores; • Significance of Local Alignment; • Significance of Global Alignment;

  50. Nucleotide Sequence Distances • Jukes-Cantor, single parameter • Kimura, 2 parameter  AC AC       GT GT 

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