PROTEOMICS    &    Proteomic Industry Sites
The scientific discipline of PROTEOMICS asks the question "What is the totality of a cell's protein matrix?".
  Proteomics wants to determine the physical properties of all the proteins that the genes encode, with a strong emphasis on
  making drugs to interactive with normal and abnormal proteins.  What is STRUCTURAL PROTEOMICS
        Transcriptome - all mRNA's made by cell at any time.          Proteome - all the proteins being made by the transcriptome.

makes chips & instruments for protein ID - Palo Alto, CA

cell wide protein inteaction maps - Paris, FR       

genomic based phaarmaceutical, New Haven, CT

Human Proteomic Initiative - Swiss Institute for Bioinformatics

               Swiss Institute of Bioinformatics, proteomics databases - Switzerland

Structural Proteomics - SanDiego, CA

Semiconductor technology for the life sciences, Santa Clara, CA

                    protein technologies - Vacaville, CA

genetic tests, prot-prot interactions - Salt Lake City


Current research in Proteomics

Proteome Sampler









Proteomics... determining 3D protein structure & integrated relationships of all of a cell's proteins.
  Often referred to as structural genomics, this new scientific discipline involves determining the 3-D structures of
large numbers of proteins. 
The goal of structural proteomics is to reveal the structures of all the key
  "functional sites" of any human protein, which should make it much easier to develop highly specific drugs.

Proteomics & the Proteomics Industry  
   What is Structural Proteomics   How to determine structure
   Known Protein Structures (3K to date)   Protein Data Bank
   Protein Structure Prediction   PROSPECT  
   Protein Families   Protein Structure Initiative
   Protein Modeling   Swiss Model
  Human Proteomics Initiative
   Individual Species Proteomics
   Genomic Modeling Projects
  Eukaryote model organisms
  Pyrococcus furiosus
  Mycobacterium tuberculosis
  Haemophilus influenzae
Proteomics Glossary of Terms   CHI Glossary

















          is the protein expression of all the proteins made by a cell, with an emphasis on developing drugs and therapies for normal and abnormal proteins. There is a scientific belief that the success of the genome sequencing projects can be applied to an analysis of all of the proteins being made by genome. Estimates suggest that the 100,000 human genes should produce, due to alternative splicing methodologies some 1,000,000+ proteins. This is a formidable task for the science of Proteomics to tackle.  At present all the big Pharma's have drug test only about 2,500 proteins.  There is a long way to go.

          Some projects designed to detect the entire PROTEOME are:

GeneBio - a division of the Swiss Institute for BioInformation of Geneva that has  molecular scanners to automate the process of separation and identification of thousands of cell proteins.  Current technology uses 2-dimensional gel electrophoresis, which separates by size and charge (see figure) . GeneBio uses automation to remove protein spots, cut the protein enzymatically into fragments, and then map the fragments in a mass spectrometer, which plots the pieces by their mass (a protein fingerprint). Pfizer Pharmaceuticals is currently analyzing protein fragments from Alzheimer patient's cerebro-spinal fluid.

Cancer Genome Anatomy Project   HTGI
- Human Tumor Gene Index project of the NCI.  A 2 year project which examines mRNA's made by cancer.  Some 50,000 genes are known to be active in one or more cancers.  Breast cancer has some 5,692 active genes, with some 277 genes not active in other tissues.  Drugs that can be found to bind to those 277 genes (or their products) might be good candidates for anti-cancer drugs. 

How does one find active genes? --> 
by Gene Chips - Affymetrix Inc. of CA produces glass micro-chip arrays coated with  cDNA pieces (DNA copies of mRNA's, but without its introns).  The cDNA's represent all the mRNA's being made by a specific cell type.  Affymetrix isolates the cell's mRNA's, tags them with a marker, pours them onto a glass chip, and then observes where mRNA and cDNA's bind.  This identifies the isolated mRNA.  Affymetrix is currently seling 2 chips:  1) which scans for 60,000 different human mRNA's and 2) one which scans for 1,700 human mRNA's related to cancers.

Some approaches that are being used to analyze all of the proteins being made by genome include:
     Association Kinetics... looks at how a protein piece may function by allowing it to interact with another protein, whose full functional role in the cell is known.  CuraGen has studied 957 molecular interactions among some 1000 proteins in yeast cell
(see fig); but remember yeast have some 6,000 genes.
     Structural Genomics... uses conventional x-ray crystallography techniques to study a proteins 3D shape.











The Amersham Pharmacia Inc. ETTAN mass spectrometer offers fast and reliable protein identification for proteomics studies. A single scan over the entire mass range provides, within minutes, real time data and high resolution spectral scans.  The instrument can use a high resolution ion gate and post source decay to analyze protein fragments.  Protein identification and characterization are offered in real time.














A Proteome Sampler of yeast proteins
shows 1,458 yeast proteins (circles) and their 1,948 interactions (lines).
Removing proteins has different effects on the yeast: lethal (red);
nonlethal (green);
slowed growth (orange);
unknown (yellow).

Hawoong Jeong and his colleagues at the
University of Notre Dame generated this map.














structural proteomics:
Often referred to as structural genomics, this discipline involves determining the 3-D structures of large numbers of proteins, ultimately accounting for an organism's entire proteome. Structural proteomics adds critical information in at least two points in the drug discovery pathway: (1) target identification, or selecting a biochemical pathway in which a drug might function, and (2) medicinal chemistry, or the actual design of compounds to modulate this metabolic pathway.

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