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The “-OMICS” or Biology on a Global Scale

The “-OMICS” or Biology on a Global Scale. Judith A. Kjelstrom, PhD Acting Director, UC Davis Biotechnology Program Lecturer in Microbiology and Molecular & Cellular Biology www.biotech.ucdavis.edu September 19, 2003.

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The “-OMICS” or Biology on a Global Scale

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  1. The “-OMICS” orBiology on a Global Scale Judith A. Kjelstrom, PhD Acting Director, UC Davis Biotechnology Program Lecturer in Microbiology and Molecular & Cellular Biology www.biotech.ucdavis.edu September 19, 2003

  2. The Human Genome Project has launched a Revolution in our Ability to Study the Processes of Life To the Bio 224 class: Genomics, Proteomics & Bioinformatics are just the beginning! New –omics are appearing every few months: metabolomics; nutrigenomics; pharmacogenomics; etc. Biotechnology is involved in all of these areas of life science research as we move in the direction of Systems Biology or Large Scale Analysis Life

  3. The New Millennium will be the Century for Life Sciences • Health Sciences • Rapid diagnostics using microarrays, nanotechnology, etc. • New medical technology such as blood-less laser surgery • Pharmaceutical Biotechnology • New vaccines, biologics for cancer treatments, etc. • Agricultural Biotechnology • genetically enhanced crops & livestock including “Pharming” • Environmental Sciences & Bioremediation–create alternate fuels via biomass conversion as well as clean up the land/water • Neurobiology– use of new imaging methods to study the brain • Microbiology – bacteria & fungi as expression systems for biotech, contain novel genes for dealing with harsh environment. Control of infectious diseases is a top priority. Engineers are also key players in these efforts to Discover the Secrets of Life

  4. A New Vocabulary is Emerging! • In Silico Biology • Systems Biology • The –omics: Genomics; Proteomics; Metabolomics; Nutrigenomics; etc. • ESTs • cDNA • BLAST • MALDI-TOF • Phred & Phrap • RNAi with siRNA • Microarrays

  5. This work in the 1990’s was just the Start!

  6. A Rough Draft of the Human Genome in 2001 was just the Beginning! We have only ~30,000-40,000 genes Nature v. 409 Feb. 15, 2001 and Science v. 291, Feb. 16, 2001

  7. Quotes from 2000: “The two technologies that will shape the next century are biotechnology and information technology” Bill Gates Microsoft ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ “The two technologies that will have the greatest impact on each other in the new millennium are biotechnology and information technology” Dr. Martina Newell-McGloughlin UCBREP (past director of UCD Biotech Program)

  8. Systems Biology is a Foundation Discipline to Bridging the Gap • Ruedi Aebersold and Leroy Hood are key researchersat Institute of Systems Biology(http://www.systemsbiology.org) • Goals: • To turn molecular biology into an exact science, with systematic and quantitative measurements. • To model a living cell “in silico” with predictive simulations. • Move to Discovery Science from hypothesis-driven science. • See Ideker, et.al., Science (2001) for more information. Computational biology Descriptive biology Use the Tools of Genomics and Bioinformatics to study the complex interactions of genes, proteins and nutrients at the cellular level

  9. We all feel good about the basics…… Proteins made from DNA message DNA The complete set of genes is called the Genome A-T-C-G….

  10. Only 1-1.5% of the total DNA are Genes

  11. Central Dogma of Molecular Biology mRNA PROTEIN TRANSCRIPTION TRANSLATION PROTEIN DNA RNA

  12. Proteins: “products made from the blueprint on the DNA” • Essential chemicals for cell structure and activities (reproduction, moving around, defense against invaders, metabolism, etc.). Insulin is a protein. • Basic unit: amino acid (~20 different ones) An average protein has ~500 amino acids. • The arrangement of these amino acids determine the type of protein made (generally speaking). • Codons (triplet code of bases) on mRNA determines the sequence. “Universal Code” • AUG-UUU-... --> methionine-phenylalanine-...

  13. The “-OME” and “–OMICS” Expand our Definitions 1. GENOMICS: The study of the GENOME; how many GENES, physical map, sequence of their DNA, structure… 2. FUNCTIONAL GENOMICS: The study oftheTRANSCRIPTOME; which, when, where and how much mRNA expressed… 3. PROTEOMICS: The study of the PROTEOME; which PROTEINS, when, where and how much…

  14. LEVEL OF COMPLETE SET OF GENE ANALYSIS mRNA PROTEIN GENOME TRANSLATION TRANSCRIPTOME TRANSCRIPTION PROTEOME

  15. Let’s investigate some of the Hot Areas of Life Sciences in more detail: • Genomics • Microarrays for global studies • RNAi for gene silencing • Bioinformatics • Merging biology with computer science • Proteomics • Metabolomics • Pharmacogenomics • Nutrigenomics • Agricultural Biotech • Biophotonics

  16. The Human Genome Project is complete, but…….. • What does it all mean? • How can I store all this genetic code (>3 billion bases)? • How can I access related databases? • How can we share data in other databases over the web? • What do these ~40,000 genes do? • Are there related genes in other life forms? Biologists need Help from Computer Scientists and Mathematicians!

  17. Biological Data comes in many Forms: • DNA sequence with SNPs • mRNA (expressed sequences as cDNA) • Proteins • electrophoretic gel patterns • mass spectrometry patterns • amino acid sequence • models of tertiary structures • Cells/Tissues • in situ hybridization • antibody staining • X rays or MRI images • Microarray spots on DNA or proteins chips

  18. DNA Chip Technology can help find new drugs for cancer therapy Each spot on chip has ssDNA (20-mers) from a different gene mRNA Thousands of genes can be analyzes at one time ssDNA is added to chip UV light The color of the spot indicates which genes are being turned on. Yellow = gene is on (in both conditions)

  19. If you are new to microarrays: • This Microarray animation can teach you the basics as well as act as a learning module: • http://www.bio.davidson.edu/courses/genomics/chip/chip.html

  20. RNAi (RNA interference) is called the Breakthrough of 2002(www.RNAinews.com) • The term RNAi was coined in 1998 by Andrew Fire and Craig Mello in Nature. • Nobel laureate, Phillip Sharp, a biologist at MIT (www.mit.edu) called it, “ the most important and exciting breakthrough of the last decade, perhaps multiple decades.” He is a leader in this new area. • Short strands of dsRNA called siRNA (short interference RNA) exist naturally in the cells of many species. • The dsRNA is cleaved by the dicer enzyme into siRNA molecules (~21-23bp) • These siRNA molecules bind to the RISC protein complex, which then forms a complex with the specific mRNA, which leads to digestion of the mRNA • RNAi is straightforward: Block the expression of a certain gene, then observe what happens. This is the basis of “knockouts” through antisense technology or ribozymes. RNAi just works better. • RNAi is revolutionizing the field of functional genomics. Silencing genes quickly and easily should give scientists new windows into how genes are involved in cellular processes. • RNAi techniques are analogous to Gene Knockout Models for identifying and validating drug targets. Censors of the Genome Sci. Am., Aug 2003

  21. Bioinformatics: “The Evolution of Tools” From the New Yorker

  22. Biology in the Computer Age • 21st century - biologists collect data faster than they can interpret it…. • BIOINFORMATICS is the science of using information to understand biology • It is the BIOLOGISTS TOOLBOX to help answer biological questions

  23. “14 Letters that Spell the Future” • Washington Post (Aug 2, 2001) • Bioinformatics is the new buzzword! • It is difficult to define but a good one is: “The art and science of using computational tools to find answers to biological questions”

  24. NCBI National Institute for Biotechnological Information http://www.ncbi.nlm.nih.gov/ Mission: to develop new information technologies to advance understanding of our genetic legacy and its role in health and disease.

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