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Proteomics

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Proteomics Session 1 Introduction Some basic concepts in biology and biochemistry The hierarchy of biological organism The micro environment: Cell DNA vs. chromosome ... – PowerPoint PPT presentation

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Title: Proteomics


1
Proteomics
  • Session 1
  • Introduction

2
Some basic concepts in biology and biochemistry
3
The hierarchy of biological organism
From molecule to organism
4
The micro environment Cell
5
DNA vs. chromosome
DNA
Chromosome
6
Central dogma the story of life
DNA
RNA
Protein
7
DNA structure
8
The basic unit in DNA
9
From DNA to Protein
1. Transcription
2. Translation
10
Step1 Transcription, generation of mRNA
11
Step2 Translation, protein assembly
Amino acid carrier tRNA
12
Peptide bond formation
Peptide Chain
13
Protein structure
14
The bonds contribute to protein structure
15
Proteins are the molecule tools for most cellular
functions
16
What is bioinformatics?
Lets take minutes to see the hot topic
bioinformatics
17
What is bioinformatics?
  • (Molecular) Bio informatics
  • One idea for a definition?
  • Bioinformatics is conceptualizing biology in
    terms of molecules (in the sense of
    physical-chemistry) and then applying
    informatics techniques (derived from
    disciplines such as applied math and statistics)
    to understand and organize the information
    associated with these molecules, on a
    large-scale.
  • Bioinformatics is MIS for Molecular Biology
    Information. It is a practical discipline with
    many applications.

18
Bioinformatics - History
Single Structures Modeling Geometry Forces
Simulation Docking Sequences, Sequence-Structure
Relationships Alignment Structure Prediction Fold
recognition Genomics Dealing with many
sequences Gene finding Genome Annotation
Databases Integrative Analysis Expression
Proteomics Data Data mining Simulation again.
19
Growth of biological databases
GenBank BASEPAIR GROWTH
Source GenBank
3D StructuresGrowth
Source http//www.rcsb.org/pdb/holdings.html
20
What bioinformatics can do for us?
21
Example Drug Discovery
  • Target Identification
  • Which protein to inhibit?
  • Lead discovery optimization
  • What sort of molecule will bind to this protein?
  • Toxicology
  • Side effects, target specificity
  • Pharmacokinetics
  • Metabolization and transport

22
Drug Development Life Cycle
Discovery (2 to 10 Years)
Preclinical Testing (Lab and Animal Testing)
Phase I (20-30 Healthy Volunteers used to check
for safety and dosage)
With the aid of bioinformatics
Phase II (100-300 Patient Volunteers used to
check for efficacy and side effects)
Phase III (1000-5000 Patient Volunteers used to
monitor reactions to long-term drug use)
600-700 Million!
FDA Review Approval
Post-Marketing Testing
Years
0 2 4
6 8 10 12
14 16
7-15 years
23
Drug lead screening
5,000 to 10,000 compounds screened
250 Lead Candidates in Preclinical
Testing
5 Drug Candidates enter Clinical Testing 80
Pass Phase I
30Pass Phase II
80 Pass Phase III
One drug approved by the FDA
24
Drug Lead Screening Docking
?
  • Complementarily
  • Shape
  • Chemical
  • Electrostatic

25
Introduction to proteomics
26
Whats proteomics ?
"The analysis of the entire protein complement
expressed by a genome, or by a cell or tissue
type. Wasinger VC et al Progress with
gene-product mapping of the mollicutes
Mycoplasma genitalium. Electrophoresis 16 (1995)
1090-1094
Two most applied technologies
1. 2-D electrophoresis
separation of complex protein
mixtures 2. Mass spectrometry
Identification
and structure analysis
27
Why proteomics becomes an important discipline
  • Significant DNA sequencing results
  • 45 microorganism genomes have been sequenced and
    170 more are in progress
  • 5 eukaryotes have been completed
  • Saccharomyces cerevisiae
  • Schizosaccharomyces pombe
  • Arabodopsis thaliana
  • Caenorhabditis elegans
  • Drosophilia melanogaster
  • Rice, Mouse and Human are nearly done
  • However, 2/3 of all genes identified have no
    known function

28
Only DNA sequence is not enough
  • Structure
  • Regulation
  • Information
  • Computers cannot determine which of these 3 roles
    DNA play solely based on sequence (although we
    would all like to believe they can)

Those are what we need to know about proteins
29
Introduction to Proteomics
  • Definitions
  • 1. Classical - restricted to large scale
    analysis of gene products involving only proteins
    (small view)
  • 2. Inclusive - combination of protein studies
    with analyses that have genetic components such
    as mRNA, genomics, and yeast two-hybrid (bigger
    view)
  • Dont forget that the proteome is dynamic,
    changing to reflect the environment that the cell
    is in.

30
1 gene 1protein?
  • 1 gene is no longer equal to one protein
  • The definition of a gene is debatable..(ORF,
    promoter, pseudogene, gene product, etc)
  • 1 gene how many proteins? (never known)

31
Why Proteomics?
32
Differential protein expression
DNA
RNA
Protein
Transcription
Translation
x4
x1
Scenario 1 can be analyzed by microarray
technology
DNA
RNA
Protein
Transcription
Translation
x3
Scenario 2 can be solved by proteomics
technology
DNA
RNA
Protein
Transcription
Translation
x3
33
Co- and Post-translational modification
Co-translational modified
Post-translational modified
34
What proteomics can answer
  • Protein identification
  • Protein Expression Studies
  • Protein Function
  • Protein Post-Translational Modification
  • Protein Localization and Compartmentalization
  • Protein-Protein Interactions

35
General classification for Proteomics
  • Protein Expression comparison (beginning)
  • Quantitative study of protein expression between
    samples that differ by some variable
  • Structural Proteomics (simulation)
  • Goal is to map out the 3-D structure of proteins
    and protein complexes
  • Functional Proteomics (everything)
  • To study protein-protein interaction, 3-D
    structures, cellular localization and PTMS in
    order to understand the physiological function of
    the whole set of proteome.
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