The Cell, Central Dogma and Human Genome Project.

The Cell, Central Dogma and

Human Genome Project

A Eukaryotic Cell (there is nucleus)

Central Dogma

Transcription and translation

Fundamentals of Nucleic Acids

DNA Base Pair & Double Helix

Strands come in pairs.

Alternating sugar-phosphate backbone A,T,G,C variability in the side groups

Nucleotide bonds are hydrogren bonds

3' ATTAGCCCAT 5'5' TAATCGGGTA 3‘

the string "attagcccat" is bonded to its complement "atgggctaat".

From DNA to protein, Eukaryotes vs. Prokaryotes

From Gene Code to Amino Acid: Codon Table

I. Protein Molecular Structure

a) Protein is a polymer of amino acids.

20 Amino Acids ( Functional Groups)

Peptide Bond Formation

Human genome project (1990 - 2003)Goal: to determine the complete sequence of the 3 billion DNA subunits (bases), identify all human genes, and make them accessible for further biological study. Ref: http://www.ornl.gov/sci/techresources/Human_Genome/home.shtml http://www.ddj.com/184410424 (How Perl saved the Human Genome project?)

Major Database and Data collection methods:Genbank: (www.ncbi.nih.gov) DNA sequence: shortgun gene sequencing (molecular biology + computation)Protein sequence: ORF finder, theoretical translation, Experimental: Proteolysis +Mass spectrometry

Protein structure db: (www.pdb.org) x-ray crystallography, Nuclear Magnetic Resonance(NMR) spectroscopyProtein structure modeling: http://swissmodel.expasy.org//SWISS-MODEL.html

Genomewide expression data (RNA): Gene chip (microarray technology) special gene chips: microRNA chip SNP chipProtein-protein interaction (Proteomics): 2D gel, mass spectrometry

NCBI (Natl Center Biotech Information) - GenBank http://www.ncbi.nlm.nih.gov/

EBI (European Bioinformatics Institute) - EMBL http://www.ebi.ac.uk/

NIAS, Japan (National Institute of Agrobiological systems)http://www.dna.affrc.go.jp/ (genebank, DNA and proteins)

KEGG http://www.genome.jp/kegg/pathway.html (pathways database)

ExPASy - SwissProt and TrEMBL: http://www.expasy.org/sprot Database of annotated proteinshttp://swissmodel.expasy.org//SWISS-MODEL.htmlDatabase for predicting protein structure using homology modeling

Prosite: http://kr.expasy.org/prositeDatabase of protein active sites

Structure Databases: PDB (Protein Data Bank): http://www. pdb.org/ Data base of Protein tertiary structuresSCOP: http://scop.mrc-lmb.cam.ac.uk/scopCATH: http://www.biochem.ucl.ac.uk/bsm/cath

Primary Biological information databases

http://www.ncbi.nlm.nih.gov/Tools and Tutorial: BLAST, Structure, PubMed, OMIM, Taxbrowser http://www.ncbi.nlm.nih.gov/IEB/ (Information Engineering)http://www.ncbi.nlm.nih.gov/Education/

Significance of the Genomics Revolution• data driven biology– functional genomics– comparative genomics– systems biology• molecular medicine– identification of genetic components of various maladies– diagnosis/prognosis from sequence/expression– gene therapy• pharmacogenomics– developing highly targeted drugs– predicting adverse effects or efficacy on individual basis• toxicogenomics– elucidating which genes are affected by various chemicals