Joint Center for Structural Genomics (JCSG)

 

Overview:

Below is a flow chart for the Joint Center for Structural Genomics (JCSG), whose main purpose is to engineer high throughput methods for determining the structures of proteins at the genome scale. As seen, JCSG is under the guidance of the Steering Committee, which advices three collaborative teams of experts: the Bioinformatics Core (BIC), the Crystallomics Core (CC) and the Structure Determination Core (SDC).

 

Click anywhere on the chart to find more information about each JCSG member or scroll down for more information.

 

 

 

 

Joint Center for Structural Genomics (JCSG)

The JCSG project is a joint collaboration between various groups. Its goals include:

  1. Implementation of a pilot production system to rapidly determine a large number of high-quality protein structures.

  2. Deliver over five years of structures of about two thousand proteins.

  3. Contribute significantly to the objectives of the NIH's Protein Structure Initiative.

  4. Create a full scale Structural Genomics Center.

 

All of the Cores are intimately intertwined so that JCSG functions as a "learning environment" for developing new methods for all aspects of structural genomics. The whole group acts in the follow sequence: target selection, expression and purification, crystallization, diffraction and structure determination, and structure refinement and validation.

 

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Steering Committee

The Steering Committee guides, directs, and leads the core groups of JCSG. One of the Committee's functions is species and target selection. C. elegans was chosen as the initial target selection because the fully sequenced genome has been mostly annotated and is publicly available. Once the production system is operational, the Steering Committee will determine which eukaryotic genomes, including human, mouse, and Drosophila, will be included in the target selection process. Additionally, the Committee reviews which proteins are deposited into the Protein Data Bank (PDP).

 

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Bioinformatics Core (BIC)

The BIC directs target selection, informatics, and validation. A major goal of human genome research is to identify all of the coding protein sequences, its biological function, and association with molecular diseases. This goal requires correlating protein sequences with structure and function. Unfortunately, there are only a few thousand unique protein structures that are known, compared to well over 100,000 gene sequences.

 

The major institutions that form the Bioinformatics Core include the

San Diego Supercomputer Center (SDSC) and the

University of California at San Diego (UCSD)

 

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Crystallomics Core (CC)

The CC is responsible for producing highly purified protein samples and diffraction quality crystals and passing the crystals to the Structure Determination Core. Since the main goal of JCSG is the determination of a large number of novel-fold structures involved in signaling, a wide variety of proteins, including extracellular, intracellular, and integral membrane, will have to be prepared and crystallized. Currently, the nanoliter-crystallization high throughput robotics system is capable of assembling 11,500 crystallization trials per day at the 40 nanoliter level, and commercial crystallization robots can perform at most 5,000 trials per day, thus enabling less protein to be required for crystallization trials. When finished, the second generation crystallization system will be able to perform 135,000 trials a day, thus allowing the Crystallomics Core to increase the number of experiments done in a day and while reducing the amount of proteins required per trial and increasing the probability for success.

 

Here are the major institutions that form the Crystallomics Core.

Genomics Institute for the Novartis Research Foundation (GNF)

Salk Institute

The Scripps Research Institute (TSRI)

 

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Structure Determination Core (SDC)

The SDC is responsible for crystal handling, data collection and analysis, and structure determination and refinement. The SDC makes use of currently available resources and also co-develops new ones. Additionally, it makes use of the Advanced Light Source (ALS) beam line 5.0.3 within the framework of GNF. The ALS beam line serves as a prototype for the automation systems required for sample mounting and analysis, which was completed in summer 2000.

 

Below are the major institutions involved with the SDC:

A Stanford Linear Accelerator Center (SLAC) division, the Stanford Synchrotron Radiation Laboratory (SSRL)

Advanced Light Source (ALS), part of the Lawrence Berkeley National Laboratory

 

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