Instructor Prof. Chandrama P. Upadhyaya 220, Life Sciences Building ,

Teaching Assistant Mr. Eom Hee-Seok 209 Life Sciences Building ,

Molecular Biology Fourth Edition Robert F. Weaver Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Evaluation Three examinations counting 35% each. - Mid term Exam (date to be announce) - Final Exam (date to be announce) Attendance 20% Home work 10%

Chapter 1: Basic mechanism of Transcription Chapter 2 : Post Transcriptional event: Messenger RNA processing I_Splicing Chapter 3: Messenger RNA processing II _ Capping and Polyadenylation Chapter 4: Other RNA Processing Events A: RNA & Transcription: DETAILS 2

Chapter 5: Mechanism of Translation I_ Initiation Chapter 6: Mechanism of Translation II_ Elongation and Termination Chapter 7: Ribosomal and Transfer RNA B: Protein Synthesis or Translation: Details 3

C: DNA and Replication mechanism Chapter 8: DNA Replication I: Basic Mechanism and Enzymology Chapter 9: DNA Replication II: Detailed Mechanism Chapter 10: Homologous Recombination Chapter 11: Genomics. Proteomics and Bioinformatics 1 DNA RNA Protein

INTRODUCTION TO GENOMICS, BIOINFORMATICS & PROTEOMICS Chapter 1

We are in the midst of a "Golden Era" of biology. The revolution is mostly about treating biology as an information science, not only specific biochemical technologies.

GENOMICS  Study of sequences, gene organization & mutations at the DNA level  This also deals with the study of information flow within a cell

Central Dogma DNA RNA Protein Genotype RNA function & structure Protein sequence Protein structure Protein Function Phenotype

THE HUMAN GENOME PROJECT 3 billion bases 30,000 genes

Would it be important to know your personal DNA sequence? Would you want to know if you were susceptible to a disease? Why or why not?

How to characterize new diseases? What new treatments can be discovered? How do we treat individual patients? Tailoring treatments? IMPACT OF GENOMICS ON MEDICINE

IMPLICATIONS FOR BIOMEDICINE Physicians will use genetic information to diagnose and treat disease. Virtually all medical conditions have a genetic component Faster drug development research: (pharmacogenomics) Individualized drugs All Biologists/Doctors will use gene sequence information in their daily work

BIOMARKERS AND GENE EXPRESSION normal malignant

WHAT IS BIOINFORMATICS? Interface of biology and computers Conceptualizing biology in terms of molecules and then applying “informatics” techniques from math, computer science, and statistics to understand and organize the information associated with these molecules on a large scale What is bioinformatics?

HOW DO WE USE BIOINFORMATICS? Store/retrieve biological information (databases) Retrieve/compare gene sequences Predict function of unknown genes/proteins Search for previously known functions of a gene Compare data with other researchers Compile/distribute data for other researchers

GenBankEMBLDDBJ Housed at EBI European Bioinformatics Institute There are three major public DNA databases Housed at NCBI National Center for Biotechnology Information Housed in Japan Go to NCBI website

SIMILARITY SEARCH: BLAST  A tool for searching gene or protein sequence databases for related genes of interest  The structure, function, and evolution of a gene may be determined by such comparisons  Alignments between the query sequence and any given database sequence, allowing for mismatches and gaps, indicate their degree of similarity

PubMed is… National Library of Medicine's search service 12 million citations in MEDLINE links to participating online journals PubMed tutorial (via “Education” on side bar)

Entrez integrates… the scientific literature; DNA and protein sequence databases; 3D protein structure data; population study data sets; assemblies of complete genomes

Entrez is a search and retrieval system that integrates NCBI databases

OMIM is… Online Mendelian Inheritance in Man catalog of human genes and genetic disorders edited by Dr. Victor McKusick, others at JHU

Books is… searchable resource of on-line books

TaxBrowser is… browser for the major divisions of living organisms (archaea, bacteria, eukaryota, viruses) taxonomy information such as genetic codes molecular data on extinct organisms

Structure site includes… Molecular Modelling Database (MMDB) biopolymer structures obtained from the Protein Data Bank (PDB) Cn3D (a 3D-structure viewer) vector alignment search tool (VAST)

DATA MINING Handling enormous amounts of data Sort through what is important and what is not Manipulate and analyze data to find patterns and variations that correlate with biological function

NEED FOR IMPROVED BIOINFORMATICS Genomics:Human Genome Project Gene array technology Comparative genomics Functional genomics Proteomics: Global view of protein function/interactions Protein motifs Structural databases

Human Genome Project

HUMAN GENOME PROJECT STATUS  Working draft of human genome reported by 2 groups allowed estimates that genome contains fewer genes than anticipated – 25,000 to 40,000  About half the genome has derived from the action of transposons  Transposons themselves have contributed dozens of genes to the genome  Bacteria also have donated dozens of genes  Finished draft is much more accurate than working draft, but there are still gaps  Information also about gene birth and death during human evolution

Applications of Genomics: Functional Genomics Functional genomics refers to those areas that deal with the function or expression of genomes. All transcripts an organism makes at any given time is an organism’s transcriptome. Use of genomic information to block expression systematically is called genomic functional profiling. Study of structures and functions of the protein products of genomes is proteomics

Transcriptomics This area is the study of all transcripts an organism makes at any given time. Create DNA microarrays and microchips that hold 1000s of cDNAs or oligos. Hybridize labeled RNAs from cells to these arrays or chips Intensity of hybridization at each spot reveals the extent of expression of the corresponding gene Microarray permits canvassing expression patterns of many genes at once. Clustering of expression of genes in time and space suggest products of these genes collaborate in some process

PROTEOMICS Uses information determined by biochemical/crystal structure methods Visualization of protein structure Make protein-protein comparisons Used to determine: conformation/folding antibody binding sites protein-protein interactions computer aided drug design

PROTEIN SEPARATIONS AND ANALYSIS  Current research in proteomics requires first that proteins be resolved, sometimes on a massive scale. Best tool for separation of many proteins at once is 2-D gel electrophoresis  After separation, proteins must be identified Best method of identification involves digestion of proteins one by one with proteases Then identify the peptides by mass spectrometry  In the future, microchips with antibodies attached may allow analysis of proteins in complex mixtures without separation

MALDI-TOF MASS SPECTROMETRY

24-38 Detecting Protein-Protein Interactions

Protein Interactions Most proteins work with other proteins to perform their functions. Several techniques are available to probe these interactions. Yeast two-hybrid analysis has been used for some time, now other methods are available Protein microarrays Immunoaffinity chromatography with mass spectrometry Other combinations

DNARNA cDNA ESTs UniGene phenotype genomic DNA databases protein sequence databases protein

bioinformatics students educators researchers institutions