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Proteomics and Cancer Japan Society for the Promotion of Science (JSPS) Science Dialogue Program at Niitsu Senior High School Niitsu, Niigata September 4th 2006 Vladimir Valera, M.D, PhD JSPS Postdoctoral fellow First Department of Surgery Niigata University 1

Proteomics 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?

Proteomics and Cancer What is Proteomics? The Proteome: the collection of proteins that are expressed by (or present in) a cell or tissue at a given moment

Proteomics and Cancer Why to study the Proteome? Genomics Genes (DNA) The Information Transcriptomics mrna The Message Proteomics Proteins The Actors

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 posttranscriptionally. Protein activity often depends on posttranslational modifications, which are not predictable from the level of the corresponding transcript. The function of a protein often depends on its localization.

Proteomics and Cancer 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? 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

Electrophoresis

Proteomics and Cancer 2 Dimensional Gel Electrophoresis (2DE) Polyacrylamide Gels 1 st dimension: pi (Isoelectric focusing) 2 nd dimension: MW (molecular weight)

Electrophoresis First Dimension: Isoelectric Focusing

2 Dimensional Gel Electrophoresis First Dimension Second Dimension

2 Dimensional Gel Electrophoresis

First Dimension S e c o n d D i m en s i o n

Differential Expression Proteomics

Proteomics and Cancer Capillary electrophoresis (CE)

Proteomics and Cancer Liquid Chromatography High Performance Liquid Chromatography (HPLC) Ion exchange chromatography (IE) Affinity chromatography (AC) 2-D Liquid Chromatography HPLC-IE, HPLC-AC etc.

Liquid Chromatography

Liquid Chromatography Size Charge Affinity

Proteomics and Cancer Mass Spectrometry (MS)

Mass Spectrometry

MALDI-TOF Mass Spectrometry

ESI Mass Spectrometry

Peptide Sequence Mass Spectra Analysis by Bioinformatics Algorithms

Proteomics and Cancer Combination of techniques: 2DE-MS, CE-MS, LC-MS

Combination of Techniques Capillary IEF Mass pectrometry

Combination of Techniques 1-D or 2-D Liquid Chromatograpy/Mass Spectrometry 2D-LC-MS

Proteomics and Cancer Microarray Technology

Protein Microarrays

Proteomics and Cancer What do we see? What do we look for?

What do we see? Bands

What do we see? Spots

What do we see? Mass Spectra

What do we see? Peptide lists

What do we look for? Expression patterns

What do we look for?

What do we look for? Expression patterns

How do we use the results?

Proteomics and Cancer How translate the results to patients care?

Proteomics and Cancer Proteomics and cancer biomarkers only? Plant genomics and proteomics Marine Biology

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

The Rice Proteome Callous 1 week after flowering

Proteomics and Marine Biology Zebrafish Medaka

Thank you for your attention! 53