proteomics and cancer

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Proteomics and Cancer

Proteomics and Cancer

Vladimir Valera, M.D, PhDJSPS Postdoctoral fellow

First Department of SurgeryNiigata University

Japan Society for the Promotion of Science (JSPS)Science Dialogue Program at Niitsu Senior High School

Niitsu, Niigata September 4th 2006

Proteomics and CancerProteomics and Cancer

• What is Proteomics?

• Why to study the Proteome?

• Why Cancer?

• How do we study the proteome

• What do we see?

• How do we use the results?

• How translate the results to patients’ care?

• Proteomics and Cancer only?


• What is Proteomics?

The Proteome: the collection of proteins that are expressed by (or present in) a cell or tissue at a given moment


• Why to study the Proteome?

Genomics Genes (DNA)

The Information

Transcriptomics mRNA

The Message

Proteomics Proteins

The Actors

Why to study the Proteome?Why to study the Proteome?

• The function of a protein depends on its structure and interactions, neither of which can be predicted accurately based on sequence information alone

• Genomics and Transcriptomics are coarse tools for large-scale functional analysis.

• The abundance of a given transcript may not reflect the abundance of the corresponding protein.

• Protein diversity is generated post-transcriptionally.

• Protein activity often depends on post-translational modifications, which are not predictable from the level of the corresponding transcript.

• The function of a protein often depends on its localization.


•Why Cancer?Cancer is one of the main causes of death in the world

Is a public health problem

Proteomics will help to the identification of Genes and Proteins responsible for or implicated in the disease

Potentially curable

Proteomics will allow early detection

It is cheaper to prevent than to treat the disease

How do we study the proteome?How do we study the proteome?

• Electrophoresis

Gel electrophoresis

2 Dimensional Electrophoresis (2DE)

Capillary electrophoresis (CE)

• Liquid Chromatography (LC)

• Mass Spectrometry (MS)

• Combination: 2DE-MS, CE-MS, LC-MS

• Microarray Technology

ElectrophoresisElectrophoresis


• 2 Dimensional Gel Electrophoresis (2DE)

Polyacrylamide Gels

1st dimension: pI(Isoelectric focusing)

2nd dimension: MW (molecular weight)

ElectrophoresisElectrophoresis

First Dimension: Isoelectric Focusing

First Dimension Second Dimension

2 Dimensional Gel Electrophoresis2 Dimensional Gel Electrophoresis

2 Dimensional Gel Electrophoresis2 Dimensional Gel Electrophoresis

First Dimension

Second

Dimension

Differential Expression Proteomics

Differential Expression Proteomics


• Capillary electrophoresis (CE)


• Liquid Chromatography• High Performance Liquid Chromatography (HPLC)

• Ion exchange chromatography (IE)

• Affinity chromatography (AC)

• 2-D Liquid Chromatography• HPLC-IE, HPLC-AC etc.

Liquid ChromatographyLiquid Chromatography

Liquid ChromatographyLiquid Chromatography

Size Charge

Affinity


• Mass Spectrometry (MS)

Mass SpectrometryMass Spectrometry

MALDI-TOF Mass SpectrometryMALDI-TOF Mass Spectrometry

ESI Mass SpectrometryESI Mass Spectrometry

Mass Spectra Analysis by Bioinformatics Algorithms

Peptide SequencePeptide Sequence


• Combination of techniques:

2DE-MS, CE-MS, LC-MS

Combination of TechniquesCombination of Techniques

Capillary IEF

Mass Spectrometry

1-D or 2-D Liquid Chromatograpy/Mass

Spectrometry 2D-LC-MS

Combination of TechniquesCombination of Techniques


Microarray Technology

Protein MicroarraysProtein Microarrays


• What do we see?

• What do we look for?

Bands

What do we see?What do we see?

Spots


Mass Spectra


Peptide lists


What do we look for?What do we look for?

Expression patterns

Expression patterns


How do we use the results? How do we use the results?


• How translate the results to patients’ care?


• Proteomics and cancer biomarkers only?

•Plant genomics and proteomics

•Marine Biology

http://gene64.dna.affrc.go.jp/RPD/database_en.html

The Rice ProteomeThe Rice Proteome

Callous 1 week after flowering

Proteomics and Marine BiologyProteomics and Marine Biology

Zebrafish

Medaka

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Thank you for your attention!

Thank you for your attention!

proteomics and cancer

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