Developers -The road to our research success-

Vol.3กงA Platform for Creating a New Paradigm - Comprehensive Analysis of GPCR Genes -

Makiko Suwa
SEVENS Project: Construction of a database for
GPCR genes
Makiko Suwa : CBRC
Yukiteru Ono :
Information and Mathematical Science Laboratory Inc.
Interview : 14th Jan. 2009
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Research made possible by experts in the field of bioinformatics gathered together by CBRC

GPCRs (G-Protein-Coupled Receptors) are the focus of much attention within bioinformatics research, especially from the perspective of pharmaceutical development. GPCRs are receptors that exist on cell membranes and receive a wide variety of ligands such as neurotransmitter substances and peptides from outside the cell, and the GPCRs selectively couple with G-proteins (GI/o , Gq/11 , Gs , etc.) inside the cell. It is understood that as a result, GPCRs contribute to a diverse range of reactions within living organisms.

At present, close to 30% of drugs in distribution around the world are produced to control GPCR reactions . It is for this reason that GPCRs are considered to be an important target of research in the field of pharmaceuticals.

However, we must clarify where GPCR genes stand in the big picture if we are to use them in effectively developing new pharmaceuticals. How many human GPCR genes are there in total? How does each GPCR work? How is each GPCR activated by each type of potential ligand? We need a database that tackles these topics in a comprehensive and integrated manner.

Dr. Makiko Suwa took on the challenge of building just such a comprehensive and integrated database. The SEVENS: GPCR database and the GRIFFIN: G-protein coupling selectivity prediction system has given form and brought to fruition Suwa's quest, embodied in her remarks that กศfrom the beginning, as the researcher who have been focused on GPCR, I have wanted to know everything about all GPCRs in our body.กษ Both of these systems are now known to researchers as contributing to assist functional analysis through experimentation.

The Project to Comprehensively Examine GPCRs Begins

The Project began in July 2000 as a result of discussions concerning future research themes that were being held in a preparatory office for the establishment of CBRC. With Yutaka Akiyama, who would later become the Director of CBRC, current Director Kiyoshi Asai, and Professor Aburatani of the Research Center for Advanced Sci. and Tech., The University of Tokyo, She discussed the project. As background to the discussions, in June 2000 there had been progress in the Human Genome Project: it was announced that a draft sequence of the human genome had been finalized. The purpose of the Project became to unravel the nature of every human GPCR gene based on this result.

At the time, it was common to identify genes in the genome by searching a database for sequences that were similar to genes already identified. However, some genes could not be found using only this method. Genes of this group possess many exons, which are spread out over an extremely wide region. If a method for precisely seeking out gene regions from genome sequences could be established, a major contribution would be made to the needs of many experimental researchers, not just only in the field of pharmaceuticals. A large scale computing environment would be needed to move forward with comprehensive research of receptors. It was also realized that joint-research with experts informatics would also be required. The Project members realized that this research theme could not be followed up at universities and corporations that existed at the time. However, with the understanding that such a research theme could be tackled by the many bioinformatics experts gathered together by CBRC, steps were taken to start the Project.

The project's ultimate goal was to construct a comprehensive and integrated database for GPCR genes. In addition to already identified GPCR genes that had been expressed, the project targeted unidentified GPCR genes that are actuary coded in the human genome and are just waiting for the opportunity to express in the future. By creating a database as a platform, the group also planned to construct a tool for predicting what type of G-proteins selectively couple with certain GPCR genes.

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