The

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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

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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
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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
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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

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This work in the 1990s was just the Start!
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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
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Quotes from 2000
The two technologies that will shape the next
century are biotechnology and information
technology Bill Gates
Microsoft T
he 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)

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Systems Biology is a Foundation Discipline to
Bridging the Gap

• Ruedi Aebersold and Leroy Hood are key
  researchers at 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
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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.
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Only 1-1.5 of the total DNA are Genes
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Central Dogma of Molecular Biology
mRNA
PROTEIN
TRANSCRIPTION
TRANSLATION
PROTEIN
DNA
RNA
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(No Transcript)
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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-... --gt methionine-phenylalanine-...

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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 of the TRANSCRIPTOME which, when,
  where and how much mRNA expressed
• 3. PROTEOMICS
• The study of the PROTEOME which PROTEINS, when,
  where and how much

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

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The Human Genome Project is complete, but..

• What does it all mean?
• How can I store all this genetic code (gt3
  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!

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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

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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)
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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

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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
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Bioinformatics The Evolution of Tools
From the New Yorker
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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

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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

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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.